Search results for: kinetic and mechanistic approaches

Authors: Jeanne Leblond, Warren Viricel, Amira Mbarek

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Although several products have reached the market, gene therapeutics are still in their first stages and require optimization. It is possible to improve their lacking efficiency by the use of carefully engineered vectors, able to carry the genetic material through each of the biological barriers they need to cross. In particular, getting inside the cell is a major challenge, because these hydrophilic nucleic acids have to cross the lipid-rich plasmatic and/or endosomal membrane, before being degraded into lysosomes. It takes less than one hour for newly endocytosed liposomes to reach highly acidic lysosomes, meaning that the degradation of the carried gene occurs rapidly, thus limiting the transfection efficiency. We propose to use a new pH-sensitive lipid able to change its conformation upon protonation at endosomal pH values, leading to the disruption of the lipidic bilayer and thus to the fast release of the nucleic acids into the cytosol. It is expected that this new pH-sensitive mechanism promote endosomal escape of the gene, thereby its transfection efficiency. The main challenge of this work was to design a preparation presenting fast-responding lipidic bilayer destabilization properties at endosomal pH 5 while remaining stable at blood pH value and during storage. A series of pH-sensitive lipids able to perform a conformational switch upon acidification were designed and synthesized. Liposomes containing these switchable lipids, as well as co-lipids were prepared and characterized. The liposomes were stable at 4°C and pH 7.4 for several months. Incubation with siRNA led to the full entrapment of nucleic acids as soon as the positive/negative charge ratio was superior to 2. The best liposomal formulation demonstrated a silencing efficiency up to 10% on HeLa cells, very similar to a commercial agent, with a lowest toxicity than the commercial agent. Using flow cytometry and microscopy assays, we demonstrated that drop of pH was required for the transfection efficiency, since bafilomycin blocked the transfection efficiency. Additional evidence was brought by the synthesis of a negative control lipid, which was unable to switch its conformation, and consequently exhibited no transfection ability. Mechanistic studies revealed that the uptake was mediated through endocytosis, by clathrin and caveolae pathways, as reported for previous lipid nanoparticle systems. This potent system was used for the treatment of hypercholesterolemia. The switchable lipids were able to knockdown PCSK9 expression on human hepatocytes (Huh-7). Its efficiency is currently evaluated on in vivo mice model of PCSK9 KO mice. In summary, we designed and optimized a new cationic pH-sensitive lipid for gene delivery. Its transfection efficiency is similar to the best available commercial agent, without the usually associated toxicity. The promising results lead to its use for the treatment of hypercholesterolemia on a mice model. Anticancer applications and pulmonary chronic disease are also currently investigated.

Keywords: liposomes, siRNA, pH-sensitive, molecular switch

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Authors: David Ryan, Martin Breugst, Turlough Downes, Peter A. Byrne, Gerard P. McGlacken

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An ambident nucleophile is a nucleophile that possesses two or more distinct nucleophilic sites that are linked through resonance and are effectively “in competition” for reaction with an electrophile. Examples include enolates, pyridone anions, and nitrite anions, among many others. Reactions of ambident nucleophiles and electrophiles are extremely prevalent at all levels of organic synthesis. The principle of hard and soft acids and bases (the “HSAB principle”) is most commonly cited in the explanation of selectivities in such reactions. Although this rationale is pervasive in any discussion on ambident reactivity, the HSAB principle has received considerable criticism. As a result, the principle’s supplantation has become an area of active interest in recent years. This project focuses on developing a model for rationalizing ambident reactivity. Presented here is an approach that incorporates computational calculations and experimental kinetic data to construct Gibbs energy profile diagrams. The preferred site of alkylation of nitrite anion with a range of ‘hard’ and ‘soft’ alkylating agents was established by ¹H NMR spectroscopy. Pseudo-first-order rate constants were measured directly by ¹H NMR reaction monitoring, and the corresponding second-order constants and Gibbs energies of activation were derived. These, in combination with computationally derived standard Gibbs energies of reaction, were sufficient to construct Gibbs energy wells. By representing the ambident system as a series of overlapping Gibbs energy wells, a more intuitive picture of ambident reactivity emerges. Here, previously unexplained switches in reactivity in reactions involving closely related electrophiles are elucidated.

Keywords: ambident, Gibbs, nucleophile, rates

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Authors: Nicole Merkle, Stefan Zander

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Ambient Assisted Living (AAL) describes a technological and methodological stack of (e.g. formal model-theoretic semantics, rule-based reasoning and machine learning), different aspects regarding the behavior, activities and characteristics of humans. Hence, a semantic representation of the user environment and its relevant elements are required in order to allow assistive agents to recognize situations and deduce appropriate actions. Furthermore, the user and his/her characteristics (e.g. physical, cognitive, preferences) need to be represented with a high degree of expressiveness in order to allow software agents a precise evaluation of the users’ context models. The correct interpretation of these context models highly depends on temporal, spatial circumstances as well as individual user preferences. In most AAL approaches, model representations of real world situations represent the current state of a universe of discourse at a given point in time by neglecting transitions between a set of states. However, the AAL domain currently lacks sufficient approaches that contemplate on the dynamic adaptions of context-related representations. Semantic representations of relevant real-world excerpts (e.g. user activities) help cognitive, rule-based agents to reason and make decisions in order to help users in appropriate tasks and situations. Furthermore, rules and reasoning on semantic models are not sufficient for handling uncertainty and fuzzy situations. A certain situation can require different (re-)actions in order to achieve the best results with respect to the user and his/her needs. But what is the best result? To answer this question, we need to consider that every smart agent requires to achieve an objective, but this objective is mostly defined by domain experts who can also fail in their estimation of what is desired by the user and what not. Hence, a smart agent has to be able to learn from context history data and estimate or predict what is most likely in certain contexts. Furthermore, different agents with contrary objectives can cause collisions as their actions influence the user’s context and constituting conditions in unintended or uncontrolled ways. We present an approach for dynamically updating a semantic model with respect to the current user context that allows flexibility of the software agents and enhances their conformance in order to improve the user experience. The presented approach adapts rules by learning sensor evidence and user actions using probabilistic reasoning approaches, based on given expert knowledge. The semantic domain model consists basically of device-, service- and user profile representations. In this paper, we present how this semantic domain model can be used in order to compute the probability of matching rules and actions. We apply this probability estimation to compare the current domain model representation with the computed one in order to adapt the formal semantic representation. Our approach aims at minimizing the likelihood of unintended interferences in order to eliminate conflicts and unpredictable side-effects by updating pre-defined expert knowledge according to the most probable context representation. This enables agents to adapt to dynamic changes in the environment which enhances the provision of adequate assistance and affects positively the user satisfaction.

Keywords: ambient intelligence, machine learning, semantic web, software agents

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Authors: Eman Nagi Gowid Selim

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Nowadays, the relevance of places to people has been questioned from different perspectives. This is attributed to the fact that many international concrete blocks were used to create multi-use public spaces in neighborhoods based on the techniques of mass-productions concepts that became one of the most effective ways in building construction, replacing the local and traditional built environment. During the last decades, the world has become increasingly globalized and citizen more mobilized, and thus, ignoring the social and environmental dimensions of the local identity. The main enquiries of the research are “How did building technologies affect urban settlement’s identity?” and “What are the impacts of technologies and globalization on local identities in urban spaces? “From this perspective, the research presents firstly, a historical review that shows how old civilizations enhance their local identities using the newly discovered building materials in each era in different urban settlement and fabrics without losing the identity. The second part of the research highlights the different approaches of building technologies and urban design to present a clear understanding of ways of applying and merging between different methodologies to achieve the most efficient urban space design. The third part aims at analyzing some international and national case studies where the form and structure of particular spaces are vital to identifying the morphological elements of urban settlements and the links existing between them. In addition, it determines how the building materials are used to enrich the vocabulary of the local identity. This part ends with the deduction of the guidelines for the integration of the environmental and social dimensions within the building technologies` approaches to enhance the sustainability of local identities and thus, ending up with redefining "Urban Identity" to guide future research in such cultural areas. Finally, the research uses the comparative methodology for applying the deduced guidelines on a national case study namely “Othman`s Towers” in corniche El Maadi, and then ends up by some results in the form of strategies for future researcher, that identifies how to ensure local identity in urban settlements using new building materials and technologies to achieve social and environmental comfort within the cultural areas.

Keywords: building technologies, cultural context, environmental approach, participatory design, social dimension, urban spaces

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Authors: Zaynab El Khattabi, Youness Tabii, Abdelhamid Benkaddour

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Nowadays, huge amount of multimedia repositories make the browsing, retrieval and delivery of video contents very slow and even difficult tasks. Video summarization has been proposed to improve faster browsing of large video collections and more efficient content indexing and access. In this paper, we focus on approaches to video summarization. The video summaries can be generated in many different forms. However, two fundamentals ways to generate summaries are static and dynamic. We present different techniques for each mode in the literature and describe some features used for generating video summaries. We conclude with perspective for further research.

Keywords: video summarization, static summarization, video skimming, semantic features

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Authors: Tarnveer Kaur

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Amino acids, as fundamental structural units of peptides and proteins, have an important role in biological systems by affecting solubility, denaturation, and activity of biomolecules. A study of these effects on thermophysical properties of model compounds in the presence of electrolytes solutions provides information about solute-solvent and solute-solute interactions on biomolecules. Ionic liquids (ILs) as organic electrolytes and green solvents are composed of an organic cation and an inorganic anion, which are liquid at ambient conditions. In the past decade, extensive investigations showed that the use of ILs as reaction media for processes involving biologically relevant compounds is promising in view of their successful application in kinetic resolution, biocatalysis, biosynthesis, separation, and purification processes. The scope of this information is valuable to explore the interactions of amino acids in ILs. To reach this purpose, apparent molar volumes of glycine/L-alanine in aqueous solutions of 1-butyl-3-methylimidazolium bromide/chloride were determined from precise density measurements at temperatures T = (288.15-318.15) K and at atmospheric pressure. Positive values for all the studied amino acids indicate the dominance of hydrophilic-ionic interactions between amino acids and Ionic liquids. The effect of temperature on volumetric properties of glycine/L-alanine in solutions has been determined from the partial molar expansibility and second-order partial molar expansibility. Further, volumetric interaction parameters and hydration number have been calculated, which have been interpreted in terms of possible solute-solvent interactions.

Keywords: ILs, amino acids, volumetric properties, hydration numbers

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Authors: N. Didiş Körhasan, D. Kaltakçı Gürel

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Many students have difficulty in learning physics from elementary to university level. In addition, students' expectancy, attitude, and motivation may be influenced negatively with their experience (failure) and prejudice about physics learning. For this reason, physics educators, who are also physics teachers, search for the best ways to make students' learning of physics easier by considering cognitive, affective, and psychomotor issues in learning. This research critically discusses the history of physics education, fundamental pedagogical approaches, and models to teach physics, and transformation of physics education with recent research.

Keywords: pedagogy, physics, physics education, science education

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Authors: Fathi M. O. Hamed, Salma F. Elkofhaifee

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The aim of this work is to detect geometrical shape objects in an image. In this paper, the object is considered to be as a circle shape. The identification requires find three characteristics, which are number, size, and location of the object. To achieve the goal of this work, this paper presents an algorithm that combines from some of statistical approaches and image analysis techniques. This algorithm has been implemented to arrive at the major objectives in this paper. The algorithm has been evaluated by using simulated data, and yields good results, and then it has been applied to real data.

Keywords: image processing, median filter, projection, scale-space, segmentation, threshold

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Authors: Fateme Montazeri

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Literary approaches towards the text of the Quran predate the modern period. Suyuti (d.1505)’s encyclopedia of Quranic sciences, Al-Itqan, provides a notable example. In the modern era, the study of the Quranic rhetorics received particular attention in the second half of the twentieth century by Egyptian scholars. Amin Al-Khouli (d. 1966), who might be considered the first to argue for the necessity of applying a literary-rhetorical lens toward the tafseer, Islamic exegesis, and his students championed the literary analysis as the most effective approach to the comprehension of the holy text. Western scholars continued the literary criticism of the Islamic scripture by applying to the Quran similar methodologies used in biblical studies. In the history of the literary examination of the Quran, the scope of the critical methods applied to the Quranic text has been limited. For, the rhetorical approaches to the Quran, in the premodern as well as the modern period, concerned almost exclusively with the lexical layer of the text, leaving the narratological dimensions insufficiently examined. Recent contributions, by Leyla Ozgur Alhassen, for instance, attempt to fill this lacunae. This paper aims at advancing the studies of the Quranic narratives by investigating the application of a literary device whose role in the Quranic stories remains unstudied, that is, “foreshadowing.” This paper shall focus on Chapter 12, “Surah al-Yusuf,” as its case study. Chapter 12, the single chapter that includes the story of Joseph in one piece, contains several instances in which the events of the story are foreshadowed. As shall be discussed, foreshadowing occurs either through a monolog or dialogue whereby one or more of the characters allude to the future happenings or through the manner in which the setting is described. Through a close reading of the text, it will be demonstrated that the usage of the rhetorical tool of foreshadowing meets a dual purpose: on the one hand, foreshadowing prepares the reader/audience for the upcoming events in the plot, and on the other hand, it highlights the psychological dimensions of the characters, their thoughts, intentions, and disposition. In analyzing the story, this study shall draw on psychoanalytical criticism to explore the layers of meanings embedded in the Quranic narrative that are unfolded through foreshadowing.

Keywords: foreshadowing, quranic narrative, literary criticism, surah yusuf

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Authors: Prateek Chharia, Biswa Bhusan Ghosh

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Graph coloring is one of the prominent concepts in graph coloring. It can be defined as a coloring of the various regions of the graph such that all the constraints are fulfilled. In this paper various graphs coloring approaches like greedy coloring, Heuristic search for maximum independent set and graph coloring using edge table is described. Graph coloring can be used in various real time applications like student time tabling generation, Sudoku as a graph coloring problem, GSM phone network.

Keywords: graph coloring, greedy coloring, heuristic search, edge table, sudoku as a graph coloring problem

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Authors: Dilek Cetin Alisar, Oya Umit Yemisci, Selin Ozen, Seyhan Sozay

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New approaches and treatment modalities are being developed to make patients more functional and independent in stroke rehabilitation. One of these approaches is transcranial direct stimulation therapy (tDCS), which aims to improve the hemiplegic upper limb function of stroke patients. tDCS therapy is not in the routine rehabilitation program; however, the studies about tDCS therapy on stroke rehabilitation was increased in recent years. Evaluate the effect of tDCS treatment on upper extremity motor function in patients with subacute stroke was aimed in our study. 32 stroke patients (16 tDCS group, 16 sham groups) who were hospitalized for rehabilitation in Başkent University Physical Medicine and Rehabilitation Clinic between 01.08.2016-20.01-2018 were included in the study. The conventional upper limb rehabilitation program was used for both tDCS and control group patients for 3 weeks, 5 days a week, for 60-120 minutes a day. In addition to the conventional stroke rehabilitation program in the tDAS group, bihemispheric tDCS was administered for 30 minutes daily. Patients were evaluated before treatment and after 1 week of treatment. Functional independence measure self-care score (FIM), Brunnstorm Recovery Stage (BRS), and Fugl-Meyer (FM) upper extremity motor function scale were used. There was no difference in demographic characteristics between the groups. There were no significant differences between BRS and FM scores in two groups, but there was a significant difference FIM score (p=0.05. FIM, BRS, and FM scores are significantly in the tDCS group, when before therapy and after 1 week of therapy, however, no difference is found in the shame group (p < 0,001). When FBS and FM scores were compared, there were statistical significant differences in tDCS group (p < 0,001). In conclusion, this randomized double-blind study showed that bihemispheric tDCS treatment was found to be superior to upper extremity motor and functional enhancement in addition to conventional rehabilitation methods in subacute stroke patients. In order for tDCS therapy to be used routinely in stroke rehabilitation, there is a need for more comprehensive, long-termed, randomized controlled clinical trials in order to find answers to many questions, such as the duration and intensity of treatment.

Keywords: cortical stimulation, motor function, rehabilitation, stroke

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Authors: John Hardy, Paul Lushenko

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he twenty-first century international security order has been fraught with challenges to the credibility and stability of the post-Cold War status quo. Although the American-led international system has rarely been threatened directly by dissatisfied states, an underlying challenge to the international security order has emerged in the form of a slow-burning abnegation of small but significant aspects of the status quo. Meanwhile, those security challenges which have threatened to destabilize order in the international system have not clearly belonged to the traditional notions of diplomacy and armed conflict. Instead, the main antagonists have been both states and non-state actors, the issues have crossed national and international boundaries, and contestation has occurred in a ‘gray zone’ between peace and war. Gray zone conflicts are not easily categorized as military operations, national security policies or political strategies, because they often include elements of diplomacy, military operations, and statecraft in complex combinations. This study applies three approaches to conceptualizing the gray zone in which many contemporary conflicts take place. The first approach frames gray zone conflicts as a form of coercive diplomacy, in which armed force is used to add credibility and commitment to political threats. The second approach frames gray zone conflicts as a form of discrete military operation, in which armed force is used sparingly and is limited to a specific issue. The third approach frames gray zones conflicts as a form of proxy war, in which armed force is used by or through third parties, rather than directly between belligerents. The study finds that each approach to conceptualizing the gray zone accounts for only a narrow range of issues which fall within the gap between traditional notions of peace and war. However, in combination, all three approaches are useful in explicating the gray zone and understanding the character of contemporary security challenges which defy simple categorization. These findings suggest that coercive diplomacy, discrete military operations, and proxy warfare provide three overlapping lenses for conceptualizing the gray zone and for understanding the gray zone conflicts which threaten international security in the early twenty-first century.

Keywords: gray zone, international security, military operations, national security, strategy

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Authors: Parth Prajapati, A. R. Srinivas

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The purpose of this paper is to validate the concept of the Lotus Mechanism using Computer Aided Engineering (CAE) tools considering the statics and dynamics through actual time dependence involving inertial forces acting on the mechanism joints. For a 1.2 m mirror made of hexagonal segments, with simple harnesses and three-point supports, the maximum diameter is 400 mm, minimum segment base thickness is 1.5 mm, and maximum rib height is considered as 12 mm. Manufacturing challenges are explored for the segments using manufacturing research and development approaches to enable use of large lightweight mirrors required for the future space system.

Keywords: dynamics, manufacturing, reflectors, segmentation, statics

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Authors: Derradji Chebli, Abdallah Bouguettoucha, Abdelbaki Reffas Khalil Guediri, Abdeltif Amrane

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The removal of Methyl Green dye (MG) from aqueous solutions using modified P-brutia cones (PBH and PBN), has been investigated work. The physical parameters such as pH, temperature, initial MG concentration, ionic strength are examined in batch experiments on the sorption of the dye. Adsorption removal of MG was conducted at natural pH 4.5 because the dye is only stable in the range of pH 3.8 to 5. It was observed in experiments that the P-brutia cones treated with NaOH (PBN) exhibited high affinity and adsorption capacity compared to the MG P-brutia cones treated with HCl (PBH) and biosorption capacity of modified P-brutia cones (PBN and PBH) was enhanced by increasing the temperature. This is confirmed by the thermodynamic parameters (ΔG° and ΔH°) which show that the adsorption of MG was spontaneous and endothermic in nature. The positive values of ΔS° suggested an irregular increase in the randomness for both adsorbent (PBN and PBH) during the adsorption process. The kinetic model pseudo-first order, pseudo-second order, and intraparticle diffusion coefficient were examined to analyze the sorption process; they showed that the pseudo-second-order model is the one that best describes the adsorption process (MG) on PBN and PBH with a correlation coefficient R²> 0.999. The ionic strength has shown that it has a negative impact on the adsorption of MG on two supports. A reduction of 68.5% of the adsorption capacity for a value Ce=30 mg/L was found for the PBH, while the PBN did not show a significant influence of the ionic strength on adsorption especially in the presence of NaCl. Among the tested isotherm models, the Langmuir isotherm was found to be the most relevant to describe MG sorption onto modified P-brutia cones with a correlation factor R²>0.999. The capacity adsorption of P-brutia cones, was confirmed for the removal of a dye, MG, from aqueous solution. We note also that P-brutia cones is a material very available in the forest and low-cost biomaterial

Keywords: adsorption, p-brutia cones, forest wastes, dyes, isotherm

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Authors: Aiydh Aljeddani, Fran Martin

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Sustainable human development is an essential component of a sustainable economic, social and environmental development. Addressing sustainable learning only through the addition of new teaching methods, or embedding certain approaches, is not sufficient on its own to support the goals of sustainable human development. This research project seeks to explore how the process of redesigning the current principles of curriculum based on the concept of sustainable learning could contribute to preparing a citizen who could later contribute towards sustainable human development. Multiple qualitative methodologies were employed in order to achieve the aim of this study. The main research methods were teachers’ field notes, artefacts, informal interviews (unstructured interview), a passive participant observation, a mini nominal group technique (NGT), a weekly diary, and weekly meeting. The study revealed that the integration of a curriculum for sustainable development, in addition to the use of innovative teaching approaches, highly valued by students and teachers in social studies’ sessions. This was due to the fact that it created a positive atmosphere for interaction and aroused both teachers and students’ interest. The content of the new curriculum also contributed to increasing students’ sense of shared responsibility through involving them in thinking about solutions for some global issues. This was carried out through addressing these issues through the concept of sustainable development and the theory of Thinking Activity in a Social Context (TASC). Students had interacted with sustainable development sessions intellectually and they also practically applied it through designing projects and cut-outs. Ongoing meetings and workshops to develop work between both the researcher and the teachers, and by the teachers themselves, played a vital role in implementing the new curriculum. The participation of teachers in the development of the project through working papers, exchanging experiences and introducing amendments to the students' environment was also critical in the process of implementing the new curriculum. Finally, the concept of sustainable learning can contribute to the learning outcomes much better than the current curriculum and it can better develop the learning objectives in educational institutions.

Keywords: redesigning, social studies and citizenship education curriculum, sustainable learning, thinking activity in a social context

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Authors: Mohammad Nasb, Muhammad Rehan, Chen Hong

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Background Meniscus defects critically alter knee function and lead to degenerative changes. Regenerative medicine applications including stem cell transplantation have showed a promising efficacy in finding alternatives to overcome traditional treatment limitations. However, stem cell therapy remains limited due to the substantially reduced viability and inhibitory microenvironment. Since tissue growth and repair are under the control of biochemical and mechanical signals, several approaches have recently been investigated (e.g., low intensity pulsed ultrasound [LIPUS]) to promote the regeneration process. This study employed LIPUS to improve growth and osteogenic differentiation of mesenchymal stem cells derived from human embryonic stem cells to improve the regeneration of meniscus tissue. Methodology: The Mesenchymal stromal cells (MSCs) were transplanted into the epicenter of the injured meniscus in rabbits, which were randomized into two main groups: a treatment group (n=32 New Zealand rabbits) including 4 subgroups of 8 rabbits in each subgroup (LIPUS treatment, MSC treatment, LIPUS with MSC and control), and a second group (n=9) to track implanted cells and their progeny using green fluorescence protein (GFP). GFP consists of the MSC and LIPUS-MSC combination subgroups. Rabbits were then subjected to histological, immunohistochemistry, and MRI assessment. Results: The quantity of the newly regenerated tissue in the combination treatment group that had Ultrasound irradiation after mesenchymal stem cells were better at all end points. Likewise, Tissue quality scores were also greater in knees treated with both approaches compared with controls and single treatment at all end points, achieving significance at twelve and twenty-four weeks [p < 0.05], and [p = 0.008] at twelve weeks. Differentiation into type-I and II collagen-expressing cells were higher in the combination group at up to twenty-four weeks. Conclusions: the combination of mesenchymal stem cells and LIPUS showed greater adhering to the sites of meniscus injury, differentiate into cells resembling meniscal fibrochondrocytes, and improve both quality and quantity of meniscal regeneration.

Keywords: stem cells, regenerative medicine, osteoarthritis, knee

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Authors: Pimpak Phumat, Sakornrat Khongkhunthian, Thomas Rades, Anette Müllertz, Siriporn Okonogi

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Self-nanoemulsifying drug delivery systems (SNEDDS) containing 4-allylpyrocatechol (AP) extracted from Piper betle were developed to enhance water solubility of AP by using modeling and design (MODDE) program. The amount of AP in each SNEDDS formulation was determined by using high-performance liquid chromatography. The formulation consisted of 20% Miglyol®812N, 40 % Kolliphor®RH40, 30 % Maisine®35-1 and 10 % ethanol was found to be the best SNEDDS that provided the highest loading capacity of AP. (141.48±15.64 mg/g SNEDDS). The system also showed miscibility with water. The particle shape and size of the AP-SNEDDS after dispersing in water was investigated by using a transmission electron microscope and photon correlation spectrophotometer, respectively. The results showed that they were a spherical shape, having a particle size of 34.27 ± 1.14 nm with a narrow size distribution of 0.17 ± 0.04. The particles showed negative zeta potential with a value of -21.66 ± 2.09 mV. Antibacterial activity of AP-SNEDDS containing 1.5 mg/mL of AP was investigated against Streptococcus intermedius. The effect of this system on S. intermedius cells was observed by a scanning electron microscope (SEM). The results from SEM revealed that the bacterial cells were obviously destroyed. Killing kinetic study of AP-SNEDDS was carried out. It was found that the killing rate of AP-SNEDDS against S. intermedius was dose-dependent and the bacterial reduction was 79.86 ± 0.45 % within 30 min. In comparison with chlorhexidine (CHX), AP-SNEDDS showed similar antibacterial effects against S. intermedius. It is concluded that SNEDDS is a potential system for enhancing water solubility of AP. The antibacterial study reveals that AP-SNEDDS can be a promising system to treat bacterial infection caused by S. intermedius.

Keywords: SNEDDS, 4-allylpyrocathecol, solubility, antibacterial activity, Streptococcus intermedius

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Authors: Comfort Aina

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Modern English, as we all know it to be a foreign language to many, will require training and re-training on the path of the teacher and learners alike. As a teacher, you cannot give that which you do not have. Teachers, many of whom are non-native speakers, are required to be competent in solving problems occurring in the teaching and learning processes. They should be conscious of up to date information about new approaches, methods, techniques as well as they should be capable in the use of information and communication technology (ICT) and, of course, should work on the improvement of their language components and competence. For teachers to be successful in these goals, they need to be encouraged and motivated. So, for EFL teachers to be successful, they are enrolled to in-service teacher training, ICT training, some of the training they undergo and the benefits accrued to it will be the focus of the paper.

Keywords: training, management, method, english language, EFL teachers

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Authors: F. Yılmaz, Y. Saylan, A. Derazshamshir, S. Atay, A. Denizli

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Quartz crystal microbalance (QCM), high-resolution mass-sensing technique, measures changes in mass on oscillating quartz crystal surface by measuring changes in oscillation frequency of crystal in real time. Protein adsorption techniques via hydrophobic interaction between protein and solid support, called hydrophobic interaction chromatography (HIC), can be favorable in many cases. Some nanoparticles can be effectively applied for HIC. HIC takes advantage of the hydrophobicity of proteins by promoting its separation on the basis of hydrophobic interactions between immobilized hydrophobic ligands and nonpolar regions on the surface of the proteins. Lysozyme is found in a variety of vertebrate cells and secretions, such as spleen, milk, tears, and egg white. Its common applications are as a cell-disrupting agent for extraction of bacterial intracellular products, as an antibacterial agent in ophthalmologic preparations, as a food additive in milk products and as a drug for treatment of ulcers and infections. Lysozyme has also been used in cancer chemotherapy. The aim of this study is the synthesis of hydrophobic nanoparticles for Lysozyme detection. For this purpose, methacryoyl-L-phenylalanine was chosen as a hydrophobic matrix. The hydrophobic nanoparticles were synthesized by micro-emulsion polymerization method. Then, hydrophobic QCM nanosensor was characterized by Attenuated total reflection Fourier transform infrared (ATR-FTIR) spectroscopy, atomic force microscopy (AFM) and zeta size analysis. Hydrophobic QCM nanosensor was tested for real-time detection of Lysozyme from aqueous solution. The kinetic and affinity studies were determined by using Lysozyme solutions with different concentrations. The responses related to a mass (Δm) and frequency (Δf) shifts were used to evaluate adsorption properties.

Keywords: nanosensor, HIC, lysozyme, QCM

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Authors: Ahmad Alwosheel, Ahmed Alqaraawi

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This work proposes a new speaker segmentation approach for two speakers. It is an online approach that does not require a prior information about speaker models. It has two phases, a conventional approach such as unsupervised BIC-based is utilized in the first phase to detect speaker changes and train a Neural Network, while in the second phase, the output trained parameters from the Neural Network are used to predict next incoming audio stream. Using this approach, a comparable accuracy to similar BIC-based approaches is achieved with a significant improvement in terms of computation time.

Keywords: artificial neural network, diarization, speaker indexing, speaker segmentation

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Authors: Sarada Prasad Pradhan, Vikram Vishal, Tariq Siddique

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With a vast area of India comprising of hilly terrain and road cut slopes, landslides and rockfalls are a common phenomenon. However, while landslide studies have received much attention in the past in India, very little literature and analysis is available regarding rockfall hazard of many rockfall prone areas, specifically in Uttarakhand Himalaya, India. The subsequent lack of knowledge and understanding of the rockfall phenomenon as well as frequent incidences of rockfall led fatalities urge the necessity of conducting site-specific rockfall studies to highlight the importance of addressing this issue as well as to provide data for safe design of preventive structures. The present study has been conducted across 10 rockfall prone road cut slopes for a distance of 15 km starting from Devprayag, India along National Highway 58 (NH-58). In order to make a qualitative assessment of Rockfall Hazard posed by these slopes, Rockfall Hazard Rating using standards for Indian Rockmass has been conducted at 10 locations under different slope conditions. Moreover, to accurately predict the characteristics of the possible rockfall phenomenon, numerical simulation was carried out to calculate the maximum bounce heights, total kinetic energies, translational velocities and trajectories of the falling rockmass blocks when simulated on each of these slopes according to real-life conditions. As it was observed that varying slope geometry had more fatal impacts on Rockfall hazard than size of rock masses, several optimizations have been suggested for each slope regarding location of barriers and modification of slope geometries in order to minimize damage by falling rocks. This study can be extremely useful in emphasizing the significance of rockfall studies and construction of mitigative barriers and structures along NH-58 around Devprayag.

Keywords: rockfall, slope stability, rockmass, hazard

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Authors: Wang Xingbo

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Computation of determinant in the form |I-X| is primary and fundamental because it can help to compute many other determinants. This article puts forward a time-reducible approach to compute determinant |I-X|. The approach is derived from the Newton’s identity and its time complexity is no more than that to compute the eigenvalues of the square matrix X. Mathematical deductions and numerical example are presented in detail for the approach. By comparison with classical approaches the new approach is proved to be superior to the classical ones and it can naturally reduce the computational time with the improvement of efficiency to compute eigenvalues of the square matrix.

Keywords: algorithm, determinant, computation, eigenvalue, time complexity

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Authors: Fuad M. Alkoot

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The main component of a machine learning system is the classifier. Classifiers are mathematical models that can perform classification tasks for a specific application area. Additionally, many classifiers are combined using any of the available methods to reduce the classifier error rate. The benefits gained from the combination of multiple classifier designs has motivated the development of diverse approaches to multiple classifiers. We aim to investigate using fractal geometry to develop an improved classifier combiner. Initially we experiment with measuring the fractal dimension of data and use the results in the development of a combiner strategy.

Keywords: fractal geometry, machine learning, classifier, fractal dimension

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Authors: Babak Forouraghi

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A genetic circuit is a collection of interacting genes and proteins that enable individual cells to implement and perform vital biological functions such as cell division, growth, death, and signaling. In cell engineering, synthetic gene circuits are engineered networks of genes specifically designed to implement functionalities that are not evolved by nature. These engineered networks enable scientists to tackle complex problems such as engineering cells to produce therapeutics within the patient's body, altering T cells to target cancer-related antigens for treatment, improving antibody production using engineered cells, tissue engineering, and production of genetically modified plants and livestock. Construction of computational models to realize genetic circuits is an especially challenging task since it requires the discovery of flow of genetic information in complex biological systems. Building synthetic biological models is also a time-consuming process with relatively low prediction accuracy for highly complex genetic circuits. The primary goal of this study was to investigate the utility of a pre-trained bidirectional encoder transformer that can accurately predict gene expressions in genetic circuit designs. The main reason behind using transformers is their innate ability (attention mechanism) to take account of the semantic context present in long DNA chains that are heavily dependent on spatial representation of their constituent genes. Previous approaches to gene circuit design, such as CNN and RNN architectures, are unable to capture semantic dependencies in long contexts as required in most real-world applications of synthetic biology. For instance, RNN models (LSTM, GRU), although able to learn long-term dependencies, greatly suffer from vanishing gradient and low-efficiency problem when they sequentially process past states and compresses contextual information into a bottleneck with long input sequences. In other words, these architectures are not equipped with the necessary attention mechanisms to follow a long chain of genes with thousands of tokens. To address the above-mentioned limitations of previous approaches, a transformer model was built in this work as a variation to the existing DNA Bidirectional Encoder Representations from Transformers (DNABERT) model. It is shown that the proposed transformer is capable of capturing contextual information from long input sequences with attention mechanism. In a previous work on genetic circuit design, the traditional approaches to classification and regression, such as Random Forrest, Support Vector Machine, and Artificial Neural Networks, were able to achieve reasonably high R2 accuracy levels of 0.95 to 0.97. However, the transformer model utilized in this work with its attention-based mechanism, was able to achieve a perfect accuracy level of 100%. Further, it is demonstrated that the efficiency of the transformer-based gene expression classifier is not dependent on presence of large amounts of training examples, which may be difficult to compile in many real-world gene circuit designs.

Keywords: transformers, generative ai, gene expression design, classification

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Authors: Aisha Al-Baroud

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The United Nations Compensation Commission (UNCC), Kuwait National Focal Point (KNFP) and Kuwait Oil Company (KOC) cooperated in a joint project to undertake comprehensive and collaborative efforts to remediate 26 million m3 of crude oil contaminated soil that had resulted from the Gulf War in 1990/1991. These efforts are referred to as the Kuwait Environmental Remediation Program (KERP). KOC has developed a Total Remediation Solution (TRS) for KERP, which will guide the Remediation projects, comprises of alternative remedial solutions with treatment techniques inclusive of limited landfills for non-treatable soil materials disposal, and relies on treating certain ranges of Total Petroleum Hydrocarbon (TPH) contamination with the most appropriate remediation techniques. The KERP Remediation projects will be implemented within the KOC’s oilfields in North and South East Kuwait. The objectives of this remediation project is to clear land for field development and treat all the oil contaminated features (dry oil lakes, wet oil lakes, and oil contaminated piles) through TRS plan to optimize the treatment processes and minimize the volume of contaminated materials to be placed into landfills. The treatment strategy will comprise of Excavation and Transportation (E&T) of oil contaminated soils from contaminated land to remote treatment areas and to use appropriate remediation technologies or a combination of treatment technologies to achieve remediation target criteria (RTC). KOC has awarded five mega projects to achieve the same and is currently in the execution phase. As a part of the company’s commitment to environment and for the fulfillment of the mandatory HSSEMS procedures, all the Remediation contractors needs to report waste generation data from the various project activities on a monthly basis. Data on waste generation is collected in order to implement cost-efficient and sustainable waste management operations. Data analytics approaches can be built on the top of the data to produce more detailed, and in-time waste generation information for the basis of waste management and collection. The results obtained highlight the potential of advanced data analytic approaches in producing more detailed waste generation information for planning and optimization of waste collection and recycling.

Keywords: waste, tencnolgies, KERP, data, soil

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Authors: Moh Rizaldi, Ali Abdurachman, Indra Perwira

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The biggest demonstration after the 1998 reforms that took place in Indonesia for several days at the end of 2019 did not eliminate the intention of the People’s Representative Council (Dewan Perwakilan Rakyat or DPR) and the President to enact the law 19 of 2019 (KPK law). There is a central issue to be highlighted, namely whether the change is intended to strengthen or even weaken the KPK. To achieve this goal, the Analysis focuses on two agency principles namely the independent principle and the control principle as seen from three things namely the legal substance, legal structure, and legal culture. The research method is normative with conceptual, historical and statute approaches. The argument from this writing is that KPK Law has cut most of the KPK's authority as a result the KPK has become symbolic or toothless in combating corruption.

Keywords: control, independent, KPK, law no. 19 of 2019

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Authors: Nompumelelo P. Mathebula, Roger A. Sheldon, Daniel P. Pienaar, Moira L. Bode

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The preparation of enantiopure Morita-Baylis-Hillman (MBH) adducts remains a challenge in organic chemistry. MBH adducts are highly functionalised compounds which act as key intermediates in the preparation of compounds of medicinal importance. MBH adducts are prepared in racemic form by reacting various aldehydes and activated alkenes in the presence of DABCO. Enantiopure MBH adducts can be obtained by employing Enzymatic kinetic resolution (EKR). This technique has been successfully demonstrated in our group, amongst others, using lipases in either hydrolysis or transesterification reactions. As these methods only allow 50% of each enantiomer to be obtained, our interest grew in exploring other enzymatic methods for the synthesis of enantiopure MBH adducts where, theoretically, 100% of the desired enantiomer could be obtained.Dehydrogenase enzymes can be employed on prochiral substrates to obtain optically pure compounds by reducing carbon-carbon double bonds or carbonyl groups of ketones. Ketoreductases have been used historically to obtain enantiopure secondary alcohols on an industrial scale. Ketoreductases are NAD(P)H-dependent enzymes and thus require nicotinamide as a cofactor. This project focuses on employing ketoreductase enzymes to selectively reduce ketones derived from Morita-Baylis-Hillman (MBH) adducts in order to obtain these adducts in enantiopure form.Results obtained from this study will be reported. Good enantioselectivity was observed using a range of different ketoreductases, however, reactions were complicated by the formation of an unexpected by-product, which was characterised employing single crystal x-ray crystallography techniques. Methods to minimise by-product formation are currently being investigated.

Keywords: ketoreductase, morita-baylis-hillman, selective reduction, x-ray crystallography

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Authors: Jaan-Willem Simon, Bertram Stier, Brett Bednarcyk, Evan Pineda, Stefanie Reese

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Textile composites, in which the reinforcing fibers are woven or braided, have become very popular in numerous applications in aerospace, automotive, and maritime industry. These textile composites are advantageous due to their ease of manufacture, damage tolerance, and relatively low cost. However, physics-based modeling of the mechanical behavior of textile composites is challenging. Compared to their unidirectional counterparts, textile composites introduce additional geometric complexities, which cause significant local stress and strain concentrations. Since these internal concentrations are primary drivers of nonlinearity, damage, and failure within textile composites, they must be taken into account in order for the models to be predictive. The macro-scale approach to modeling textile-reinforced composites treats the whole composite as an effective, homogenized material. This approach is very computationally efficient, but it cannot be considered predictive beyond the elastic regime because the complex microstructural geometry is not considered. Further, this approach can, at best, offer a phenomenological treatment of nonlinear deformation and failure. In contrast, the mesoscale approach to modeling textile composites explicitly considers the internal geometry of the reinforcing tows, and thus, their interaction, and the effects of their curved paths can be modeled. The tows are treated as effective (homogenized) materials, requiring the use of anisotropic material models to capture their behavior. Finally, the micro-scale approach goes one level lower, modeling the individual filaments that constitute the tows. This paper will compare meso- and micro-scale approaches to modeling the deformation, damage, and failure of textile-reinforced polymer matrix composites. For the mesoscale approach, the woven composite architecture will be modeled using the finite element method, and an anisotropic damage model for the tows will be employed to capture the local nonlinear behavior. For the micro-scale, two different models will be used, the one being based on the finite element method, whereas the other one makes use of an embedded semi-analytical approach. The goal will be the comparison and evaluation of these approaches to modeling textile-reinforced composites in terms of accuracy, efficiency, and utility.

Keywords: multiscale modeling, continuum damage model, damage interaction, textile composites

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Authors: Kirti Hira, A. Sajeli Begum, S. Mahibalan, Poorna Chandra Rao

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Introduction: Cancer is one of the leading causes of death worldwide. Although existing therapy effectively kills cancer cells, they do affect normal growing cells leading to many undesirable side effects. Hence there is need to develop effective as well as safe drug molecules to combat cancer, which is possible through phyto-research. The currently available plant-derived blockbuster drugs are the example for this. In view of this, an investigation was done to identify cytotoxic lead molecules from Hedyotis umbellata (Family Rubiaceae), a widely distributed weed in India. Materials and Methods: The methanolic extract of the whole plant of H. umbellata (MHU), prepared through Soxhlet extraction method was further fractionated with diethyl ether and n-butanol, successively. MHU, ether fraction (EMHU) and butanol fraction (BMHU) were lyophilized and were tested for the cytotoxic effect using 3-(4,5-Dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) assay against non-small cell lung cancer (NSCLC) A549 cell lines. The potentially active EMHU was subjected to chromatographic purification using normal-phase silica columns, in order to isolate the responsible bioactive compounds. The isolated pure compounds were tested for their cytotoxic effect by MTT assay against A549 cells. Compound-3, which was found to be most active, was characterized using IR, 1H- and 13C-NMR and MS analysis. The study was further extended to decipher the mechanism of action of cytotoxicity of compound-3 against A549 cells through various in vitro cellular models. Cell cycle analysis was done using flow cytometry following PI (Propidium Iodide) staining. Protein analysis was done using Western blot technique. Results: Among MHU, EMHU, and BMHU, the non-polar fraction EMHU demonstrated a significant dose-dependent cytotoxic effect with IC50 of 67.7μg/ml. Chromatography of EMHU yielded seven compounds. MTT assay of isolated compounds explored compound-3 as potentially active one, which inhibited the growth of A549 cells with IC50value of 14.2μM. Further, compound-3 was identified as cedrelopsin, a coumarin derivative having molecular weight of 260. Results of in vitro mechanistic studies explained that cedrelopsin induced cell cycle arrest at G2/M phase and down-regulated the expression of G2/M regulatory proteins such as cyclin B1, cdc2, and cdc25C, dose dependently. This is the first report that explores the cytotoxic mechanism of cedrelopsin. Conclusion: Thus a potential small lead molecule, cedrelopsin isolated from H. umbellata, showing antiproliferative effect mediated by G2/M arrest in A549 cells was discovered. The effect of cedrelopsin against other cancer cell lines followed by in vivo studies can be performed in future to develop a new drug candidate.

Keywords: A549, cedrelopsin, G2/M phase, Hedyotis umbellata

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Authors: Mehmet Mucuk, Ayşen Edirneligil

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Budget and current account deficits are main problems for all countries. There are different approaches about the relationship between budget deficit and current account deficit. While Keynesian view accepts that there is a casual link between these variables, Ricardian equivalence hypothesis rejects it. The aim of this study is to analyze the validity of Keynesian view for Turkish Economy using VAR analysis with the monthly data in the period of 2006-2014. In this context, it will be used Johansen Cointegration Test, Impulse-Response Function and Variance Decomposition Tests.

Keywords: budget deficit, current account deficit, Turkish economy, twin deficits

Procedia PDF Downloads 422