Search results for: antibacterial agent
167 Development and Validation of a Green Analytical Method for the Analysis of Daptomycin Injectable by Fourier-Transform Infrared Spectroscopy (FTIR)
Authors: Eliane G. Tótoli, Hérida Regina N. Salgado
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Daptomycin is an important antimicrobial agent used in clinical practice nowadays, since it is very active against some Gram-positive bacteria that are particularly challenges for the medicine, such as methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant Enterococci (VRE). The importance of environmental preservation has receiving special attention since last years. Considering the evident need to protect the natural environment and the introduction of strict quality requirements regarding analytical procedures used in pharmaceutical analysis, the industries must seek environmentally friendly alternatives in relation to the analytical methods and other processes that they follow in their routine. In view of these factors, green analytical chemistry is prevalent and encouraged nowadays. In this context, infrared spectroscopy stands out. This is a method that does not use organic solvents and, although it is formally accepted for the identification of individual compounds, also allows the quantitation of substances. Considering that there are few green analytical methods described in literature for the analysis of daptomycin, the aim of this work was the development and validation of a green analytical method for the quantification of this drug in lyophilized powder for injectable solution, by Fourier-transform infrared spectroscopy (FT-IR). Method: Translucent potassium bromide pellets containing predetermined amounts of the drug were prepared and subjected to spectrophotometric analysis in the mid-infrared region. After obtaining the infrared spectrum and with the assistance of the IR Solution software, quantitative analysis was carried out in the spectral region between 1575 and 1700 cm-1, related to a carbonyl band of the daptomycin molecule, and this band had its height analyzed in terms of absorbance. The method was validated according to ICH guidelines regarding linearity, precision (repeatability and intermediate precision), accuracy and robustness. Results and discussion: The method showed to be linear (r = 0.9999), precise (RSD% < 2.0), accurate and robust, over a concentration range from 0.2 to 0.6 mg/pellet. In addition, this technique does not use organic solvents, which is one great advantage over the most common analytical methods. This fact contributes to minimize the generation of organic solvent waste by the industry and thereby reduces the impact of its activities on the environment. Conclusion: The validated method proved to be adequate to quantify daptomycin in lyophilized powder for injectable solution and can be used for its routine analysis in quality control. In addition, the proposed method is environmentally friendly, which is in line with the global trend.Keywords: daptomycin, Fourier-transform infrared spectroscopy, green analytical chemistry, quality control, spectrometry in IR region
Procedia PDF Downloads 380166 Haematology and Reproductive Performance of Pubertal Rabbit Do Administer Crude Moringa oleifera (LAM.) Leaf Extract
Authors: Ewuola E. O., Sokunbi O. A., Oyedemi O. M., Sanni K. M
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Moringa oleifera leaf has been traditionally used in the local medicine as an ingredient in some herbal formulations for blood purifier, cholesterol reducing agent, immune and reproductive enhancers. Twenty-four pubertal rabbit are divided equally into four groups were administered with varied concentrations of crude extract of the leaves of Moringa oleifera gavage at doses of 2.5ml/kg body weight (BW) in every 48 hours for 63 days. These rabbits were allotted into four treatments and each treatment was replicated six times to investigate the effect of administered crude Moringa oleifera leaf extract (CMOLE) on haematology and reproductive performance of pubertal rabbit does. Four experimental treatments were used. The animals on the control (T1) were administered water only. Rabbits on treatments 2, 3, and 4 were administered 100ml CMOLE/L, 200ml CMOLE/L, and 300ml CMOLE/L, respectively. The does were placed on extract two weeks before mating, five weeks after mating and continued for another two weeks after kindling. Six proven untreated bucks were used for the mating of the twenty-four treated does and these bucks were randomly allotted to the does such that each buck mated at least one treated does in each treatment. The same management practices and experimental diets were given ad libitum to all animals. Blood was sampled from the gestating does at the third trimester for haematological analysis. The haematology results showed that treated rabbits with 100ml CMOLE/L with mean corpuscular volume value of 93.38fl significantly (p < 0.05) higher than those on the control which is water only (82.24fl) but not significantly different from T3 (200ml CMOLE/L) and T4 (300ml CMOLE/L) which had mean values of 91.69fl and 91.49fl, respectively. While the erythrocyte counts, leukocyte counts, haematocrit, haemoglobin concentration, mean corpuscular haemoglobin, mean corpuscular haemoglobin concentration, lymphocyte, neutrophil, monocyte, and eosinophil count were not significantly different across the treatments. For platelets, treated animals on T2 (100ml CMOLE/L) had the highest numerical value of 148.80 x 109/L which was identical with those on T3 (200ml CMOLE/L) with mean value of 141.50x109/L but significantly (p < 0.05) higher than those on T4 (300ml CMOLE/L) with mean value of 135.00 x 109/L and those on the control which had the least mean value of 126.60 x 109/L. The percentage conception rate of the treated animals was higher than those in the control group. The animals administered 300ml CMOLE/L had the apparently highest litter size of 5.75, while gestation length and litter weight tended to decline with increase in CMOLE concentrations The investigation demonstrated the potential effect of crude Moringa oleifera leaf extract on pubertal rabbit does. The administration of up to 300ml crude Moringa oleifera leaf extract per liter did not adversely affect but improved the haematological response and reproductive potential in gestating rabbit does.Keywords: conception, haematology, moringa leaf extract, rabbit does
Procedia PDF Downloads 509165 Enhancement of Hardness Related Properties of Grey Cast Iron Powder Reinforced AA7075 Metal Matrix Composites Through T6 and T8 Heat Treatments
Authors: S. S. Sharma, P. R. Prabhu, K. Jagannath, Achutha Kini U., Gowri Shankar M. C.
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In present global scenario, aluminum alloys are coining the attention of many innovators as competing structural materials for automotive and space applications. Comparing to other challenging alloys, especially, 7xxx series aluminum alloys have been studied seriously because of their benefits such as moderate strength; better deforming characteristics, excellent chemical decay resistance, and affordable cost. 7075 Al-alloys have been used in the transportation industry for the fabrication of several types of automobile parts, such as wheel covers, panels and structures. It is expected that substitution of such aluminum alloys for steels will result in great improvements in energy economy, durability and recyclability. However, it is necessary to improve the strength and the formability levels at low temperatures in aluminium alloys for still better applications. Aluminum–Zinc–Magnesium with or without other wetting agent denoted as 7XXX series alloys are medium strength heat treatable alloys. Cu, Mn and Si are the other solute elements which contribute for the improvement in mechanical properties achievable by selecting and tailoring the suitable heat treatment process. On subjecting to suitable treatments like age hardening or cold deformation assisted heat treatments, known as low temperature thermomechanical treatments (LTMT) the challenging properties might be incorporated. T6 is the age hardening or precipitation hardening process with artificial aging cycle whereas T8 comprises of LTMT treatment aged artificially with X% cold deformation. When the cold deformation is provided after solution treatment, there is increase in hardness related properties such as wear resistance, yield and ultimate strength, toughness with the expense of ductility. During precipitation hardening both hardness and strength of the samples are increasing. Decreasing peak hardness value with increasing aging temperature is the well-known behavior of age hardenable alloys. The peak hardness value is further increasing when room temperature deformation is positively supported with age hardening known as thermomechanical treatment. Considering these aspects, it is intended to perform heat treatment and evaluate hardness, tensile strength, wear resistance and distribution pattern of reinforcement in the matrix. 2 to 2.5 and 3 to 3.5 times increase in hardness is reported in age hardening and LTMT treatments respectively as compared to as-cast composite. There was better distribution of reinforcements in the matrix, nearly two fold increase in strength levels and upto 5 times increase in wear resistance are also observed in the present study.Keywords: reinforcement, precipitation, thermomechanical, dislocation, strain hardening
Procedia PDF Downloads 309164 An Analytical Metric and Process for Critical Infrastructure Architecture System Availability Determination in Distributed Computing Environments under Infrastructure Attack
Authors: Vincent Andrew Cappellano
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In the early phases of critical infrastructure system design, translating distributed computing requirements to an architecture has risk given the multitude of approaches (e.g., cloud, edge, fog). In many systems, a single requirement for system uptime / availability is used to encompass the system’s intended operations. However, when architected systems may perform to those availability requirements only during normal operations and not during component failure, or during outages caused by adversary attacks on critical infrastructure (e.g., physical, cyber). System designers lack a structured method to evaluate availability requirements against candidate system architectures through deep degradation scenarios (i.e., normal ops all the way down to significant damage of communications or physical nodes). This increases risk of poor selection of a candidate architecture due to the absence of insight into true performance for systems that must operate as a piece of critical infrastructure. This research effort proposes a process to analyze critical infrastructure system availability requirements and a candidate set of systems architectures, producing a metric assessing these architectures over a spectrum of degradations to aid in selecting appropriate resilient architectures. To accomplish this effort, a set of simulation and evaluation efforts are undertaken that will process, in an automated way, a set of sample requirements into a set of potential architectures where system functions and capabilities are distributed across nodes. Nodes and links will have specific characteristics and based on sampled requirements, contribute to the overall system functionality, such that as they are impacted/degraded, the impacted functional availability of a system can be determined. A machine learning reinforcement-based agent will structurally impact the nodes, links, and characteristics (e.g., bandwidth, latency) of a given architecture to provide an assessment of system functional uptime/availability under these scenarios. By varying the intensity of the attack and related aspects, we can create a structured method of evaluating the performance of candidate architectures against each other to create a metric rating its resilience to these attack types/strategies. Through multiple simulation iterations, sufficient data will exist to compare this availability metric, and an architectural recommendation against the baseline requirements, in comparison to existing multi-factor computing architectural selection processes. It is intended that this additional data will create an improvement in the matching of resilient critical infrastructure system requirements to the correct architectures and implementations that will support improved operation during times of system degradation due to failures and infrastructure attacks.Keywords: architecture, resiliency, availability, cyber-attack
Procedia PDF Downloads 106163 Endoscopic Stenting of the Main Pancreatic Duct in Patients With Pancreatic Fluid Collections After Pancreas Transplantation
Authors: Y. Teterin, S. Suleymanova, I. Dmitriev, P. Yartcev
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Introduction: One of the most common complications after pancreas transplantation are pancreatic fluid collections (PFCs), which are often complicated not only by infection and subsequent disfunction of the pancreatoduodenal graft (PDG), but also with a rather high mortality rate of recipients. Drainage is not always effective and often requires repeated open surgical interventions, which worsens the outcome of the surgery. Percutaneous drainage of PFCs combined with endoscopic stenting of the main pancreatic duct of the pancreatoduodenal graft (MPDPDG) showed high efficiency in the treatment of PFCs. Aims & Methods: From 01.01.2012 to 31.12.2021 at the Sklifosovsky Research Institute for Emergency Medicine were performed 64 transplantations of PDG. In 11 cases (17.2%), the early postoperative period was complicated by the formation of PFCs. Of these, 7 patients underwent percutaneous drainage of pancreonecrosis with high efficiency and did not required additional methods of treatment. In the remaining 4 patients, drainage was ineffective and was an indication for endoscopic stenting of the MPDPDG. They were the ones who made up the study group. Among them were 3 men and 1 woman. The mean age of the patients was 36,4 years.PFCs in these patients formed on days 1, 12, 18, and 47 after PDG transplantation. We used a gastroscope to stent the MPDPDG, due to anatomical features of the location of the duodenoduodenal anastomosis after PDG transplantation. Through the endoscope channel was performed selective catheterization of the MPDPDG, using a catheter and a guidewire, followed by its contrasting with a water-soluble contrast agent. Due to the extravasation of the contrast, was determined the localization of the defect in the PDG duct system. After that, a plastic pancreatic stent with a diameter of 7 Fr. and a length of 7 cm. was installed along guidewire. The stent was installed in such a way that its proximal edge completely covered the defect zone, and the distal one was determined in the intestinal lumen. Results: In all patients PDG pancreaticography revealed extravasation of a contrast in the area of the isthmus and body of the pancreas, which required stenting of the MPDPDG. In 1 (25%) case, the patient had a dislocation of the stent into the intestinal lumen (III degree according to Clavien-Dindo (2009)). This patient underwent repeated endoscopic stenting of the MPDPDG. On average 23 days after endoscopic stenting of the MPDPDG, the drainage tubes were removed and after approximately 40 days all patients were discharged in a satisfactory condition with follow-up endocrinologist and surgeon consultation. Pancreatic stents were removed after 6 months ± 7 days. Conclusion: Endoscopic stenting of the main pancreatic duct of the donor pancreas is by far the most highly effective and minimally invasive method in the treatment of PFCs after transplantation of the pancreatoduodenal complex.Keywords: pancreas transplantation, endoscopy surgery, diabetes, stenting, main pancreatic duct
Procedia PDF Downloads 85162 The Impact of Neuroscience Knowledge on the Field of Education
Authors: Paula Andrea Segura Delgado, Martha Helena Ramírez-Bahena
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Research on how the brain learns has a transcendental application in the educational context. It is crucial for teacher training to understand the nature of brain changes and their direct influence on learning processes. This communication is based on a literature review focused on neuroscience, neuroeducation, and the impact of digital technology on the human brain. Information was gathered from both English and Spanish language sources, using online journals, books and reports. The general objective was to analyze the role of neuroscience knowledge in enriching our understanding of the learning process. In fact, the authors have focused on the impact of digital technology on the human brain as well as its influence in the field of education..Neuroscience knowledge can contribute significantly to improving the training of educators and therefore educational practices. Education as an instrument of change and school as an agent of socialization, it is necessary to understand what it aims to transform: the human brain. Understanding the functioning of the human brain has important repercussions on education: this elucidates cognitive skills, psychological processes and elements that influence the learning process (memory, executive functions, emotions and the circadian cycle); helps identify psychological and neurological deficits that can impede learning processes (dyslexia, autism, hyperactivity); It allows creating environments that promote brain development and contribute to the advancement of brain capabilities in alignment with the stages of neurobiological development. The digital age presents diverse opportunities to every social environment. The frequent use of digital technology (DT) has had a significant and abrupt impact on both the cognitive abilities and physico-chemical properties of the brain, significantly influencing educational processes. Hence, educational community, with the insights from advances in neuroscience, aspire to identify the positive and negative effects of digital technology on the human brain. This knowledge helps ensure the alignment of teacher training and practices with these findings. The knowledge of neuroscience enables teachers to develop teaching methods that are aligned with the way the brain works. For example, neuroscience research has shown that digital technology is having a significant impact on the human brain (addition, anxiety, high levels of dopamine, circadian cycle disorder, decrease in attention, memory, concentration, problems with their social relationships). Therefore, it is important to understand the nature of these changes, their impact on the learning process, and how educators should effectively adapt their approaches based on these brain's changes.Keywords: digital technology, learn process, neuroscience knowledge, neuroeducation, training proffesors
Procedia PDF Downloads 59161 The Emerging Role of Cannabis as an Anti-Nociceptive Agent in the Treatment of Chronic Back Pain
Authors: Josiah Damisa, Michelle Louise Richardson, Morenike Adewuyi
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Lower back pain is a significant cause of disability worldwide and associated with great implications in terms of the well-being of affected individuals and society as a whole due to its undeniable socio-economic impact. With its prevalence on the increase as a result of an aging global population, the need for novel forms of pain management is ever paramount. This review aims to provide further insight into current research regarding a role for the endocannabinoid signaling pathway as a target in the treatment of chronic pain, with particular emphasis on its potential use as part of the treatment of lower back pain. Potential advantages and limitations of cannabis-based medicines over other forms of analgesia currently licensed for medical use are discussed in addition to areas that require ongoing consideration and research. To evaluate the efficacy of cannabis-based medicines in chronic pain, studies pertaining to the role of medical cannabis in chronic disease were reviewed. Standard searches of PubMed, Google Scholar and Web of Science databases were undertaken with peer-reviewed journal articles reviewed based on the indication for pain management, cannabis treatment modality used and study outcomes. Multiple studies suggest an emerging role for cannabis-based medicines as therapeutic agents in the treatment of chronic back pain. A potential synergistic effect has also been purported if these medicines are co-administered with opiate analgesia due to the similarity of the opiate and endocannabinoid signaling pathways. However, whilst recent changes to legislation in the United Kingdom mean that cannabis is now licensed for medicinal use on NHS prescription for a number of chronic health conditions, concerns remain as to the efficacy and safety of cannabis-based medicines. Research is lacking into both their side effect profiles and the long-term effects of cannabis use. Legal and ethical considerations to the use of these products in standardized medical practice also persist due to the notoriety of cannabis as a drug of abuse. Despite this, cannabis is beginning to gain traction as an alternative or even complementary drug to opiates, with some preclinical studies showing opiate-sparing effects. Whilst there is a paucity of clinical trials in this field, there is scope for cannabinoids to be successful anti-nociceptive agents in managing chronic back pain. The ultimate aim would be to utilize cannabis-based medicines as alternative or complementary therapies, thereby reducing opiate over-reliance and providing hope to individuals who have exhausted all other forms of standard treatment.Keywords: endocannabinoids, cannabis-based medicines, chronic pain, lower back pain
Procedia PDF Downloads 199160 Changing MBA Identities: Using Critical Reflection inside and out in Finding a New Narrative
Authors: Keith Schofield, Leigh Morland
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Storytelling is an established means of leadership and management development and is also considered a form of leadership of self and others in its own right. This study focuses on the utility of storytelling in the development of management narratives in an MBA programme; sources include programme participants as well as international recruiters, whose voices are often only heard in terms of economic contribution and globalisation. For many MBA candidates, the return to study requires the development of a new identity which complements their professional identity; each candidate has their own journey and expectations, the use of story can enable candidates to explore their aspirations and assumptions and give voice to previously unspoken ideas. For international recruitment, the story of market development and change must be captured if MBAs are to remain fit for purpose. If used effectively, story acts as a form of critical reflection that can inform the learning journeys of individuals, emerging identities as well as the ongoing design and development of programmes. The landscape of management education is shifting; the MBA begins to attract a different kind of candidate, some are younger than before, others are seeking validation for their existing work practices, yet more are entrepreneurial and wish to capitalise on an institutional experience to further their career. There is a shift in context, creating uncertainty and ambiguity for programme managers and recruiters, thus requiring institutions to create a new MBA narrative. This study utilises Lego SeriousPlay as the means to engaging programme participants and international agents in telling the story of their MBA. We asked MBA participants to tell the story of their leadership and management aspirations and compare these to stories of their development journeys, allowing for critical reflection of their respective development gaps. We asked international recruiters, who act as university agents and promote courses in the student’s country of origin, to explore their mental models of MBA candidates and their learning agenda. The purpose of this process was to explore the agent’s perception of the MBA programme and to articulate the student journey from a recruitment perspective. The paper’s unique contribution is in combining these stories in order to explore the assumptions that determine programme design. Data drawn from reflective statements together with images of Lego ‘builds’ created the opportunity for reflection between the mental models of these groups. Findings will inform the design of the MBA journey and experience; we review the extent to which the changing identities of learners are congruent with programme design. Data from international recruiters also determines the extent to which marketing and recruitment strategies identify with would be candidates.Keywords: critical reflection, programme management, recruitment, storytelling
Procedia PDF Downloads 225159 An Acyclic Zincgermylene: Rapid H₂ Activation
Authors: Martin Juckel
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Probably no other field of inorganic chemistry has undergone such a rapid development in the past two decades than the low oxidation state chemistry of main group elements. This rapid development has only been possible by the development of new bulky ligands. In case of our research group, super-bulky monodentate amido ligands and β-diketiminate ligands have been used to a great success. We first synthesized the unprecedented magnesium(I) dimer [ᴹᵉˢNacnacMg]₂ (ᴹᵉˢNacnac = [(ᴹᵉˢNCMe)₂CH]-; Mes = mesityl, which has since been used both as reducing agent and also for the synthesis of new metal-magnesium bonds. In case of the zinc bromide precursor [L*ZnBr] (L*=(N(Ar*)(SiPri₃); (Ar* = C₆H₂{C(H)Ph₂}₂Me-2,6,4, the reduction with [ᴹᵉˢNacnacMg]₂ led to such a metal-magnesium bond. This [L*ZnMg(ᴹᵉˢNacnac)] compound can be seen as an ‘inorganic Grignard reagent’, which can be used to transfer the metal fragment onto other functional groups or other metal centers; just like the conventional Grignard reagent. By simple addition of (TBoN)GeCl (TBoN = N(SiMe₃){B(DipNCH)₂) to the aforesaid compound, we were able to transfer the amido-zinc fragment to the Ge center of the germylene starting material and to synthesize the first example of a germanium(II)-zinc bond: [:Ge(TBoN)(ZnL*)]. While these reactions typically led to complex product mixture, [:Ge(TBoN)(ZnL*)] could be isolated as dark blue crystals in a good yield. This new compound shows interesting reactivity towards small molecules, especially dihydrogen gas. This is of special interest as dihydrogen is one of the more difficult small molecules to activate, due to its strong (BDE = 108 kcal/mol) and non-polar bond. In this context, the interaction between H₂ σ-bond with the tetrelylene p-Orbital (LUMO), with concomitant donation of the tetrelylene lone pair (HOMO) into the H₂ σ* orbital are responsible for the activation of dihydrogen gas. Accordingly, the narrower the HOMO-LUMO gap of tertelylene, the more reactivity towards H₂ it typically is. The aim of a narrow HOMO-LUMO gap was reached by transferring electropositive substituents respectively metal substituents with relatively low Pauling electronegativity (zinc: 1.65) onto the Ge center (here: the zinc-amido fragment). In consideration of the unprecedented reactivity of [:Ge(TBoN)(ZnL*)], a computational examination of its frontier orbital energies was undertaken. The energy separation between the HOMO, which has significant Ge lone pair character, and the LUMO, which has predominantly Ge p-orbital character, is narrow (40.8 kcal/mol; cf.∆S-T= 24.8 kcal/mol), and comparable to the HOMO-LUMO gaps calculated for other literature known complexes). The calculated very narrow HOMO-LUMO gap for the [:Ge(TBoN)(ZnL*)] complex is consistent with its high reactivity, and is remarkable considering that it incorporates a π-basic amide ligand, which are known to raise the LUMO of germylenes considerably.Keywords: activation of dihydrogen gas, narrow HOMO-LUMO gap, first germanium(II)-zinc bond, inorganic Grignard reagent
Procedia PDF Downloads 181158 Community Singing, a Pathway to Social Capital: A Cross-Cultural Comparative Assessment of the Benefits of Singing Communities in South Tyrol and South Africa
Authors: Johannes Van Der Sandt
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This quantitative study investigates different approaches of community singing, in building social capital in South Tyrol, Italy, and South Africa. The impact of the various approaches of community singing is examined by investigating the main components of social capital, namely, social norms and obligations, social networks and associations and trust, and how these components are manifested in two different societies. The research is based on the premise that community singing is an important agent for the development of social capital. It seeks to establish in what form community singing can best enhance the social capital of communities in South Tyrol that are undergoing significant changes in the ways in which social capital is generally being generated on account of demographic, economic, technological and cultural changes. South Tyrol and South Africa share some similarities in the management of their multi-cultural composition. By comparing the different approaches to community singing in two multi-cultural societies, it is hoped to gain insight, and an understanding of the connections between culture, social cohesion, identity and therefore to be able to add to the understanding of the building of social capital through community singing. Participation in music contributes to the growth of social capital in communities, this is amongst others the finding of an ever increasing amount of research. In sociological discourses on social capital generation, the dimension of community music making is recognized as an important factor. Trust and mutual cooperation are products when people listen to each other, when they work or play together, and when they care about each other. This is how social capital develops as an important shared resource. Scholars of Community Music still do not agree on a short and concise definition for Community Music. For the purpose of this research, the author concurs with the definition of Community Music of the Community Music Activity commission of the International Society of Music Education as having the following characteristics: decentralization, accessibility, equal opportunity, and active participation in music-making. These principles are social and political ones, and there can be no doubt that community music activity is more than a purely musical one. Trust, shared norms and values civic and community involvement, networks, knowledge resources, contact with families and friends, and fellowship are key components in fostering group cohesion and social capital development in a community. The research will show that there is no better place for these factors to flourish than in a community singing group. Through this comparative study, it is the aim to identify, analyze and explain similarities and differences in approaches to community across societies that find themselves in a rapid transition from traditional cultural to global cultural habits characterized by a plurality of orientation points, with the aim to gain a better understanding of the various directions South Tyrolean singing culture can take.Keywords: community music, multicultural, singing, social capital
Procedia PDF Downloads 283157 Application of Geosynthetics for the Recovery of Located Road on Geological Failure
Authors: Rideci Farias, Haroldo Paranhos
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The present work deals with the use of drainage geo-composite as a deep drainage and geogrid element to reinforce the base of the body of the landfill destined to the road pavement on geological faults in the stretch of the TO-342 Highway, between the cities of Miracema and Miranorte, in the State of Tocantins / TO, Brazil, which for many years was the main link between TO-010 and BR-153, after the city of Palmas, also in the state of Tocantins / TO, Brazil. For this application, geotechnical and geological studies were carried out by means of SPT percussion drilling, drilling and rotary drilling, to understand the problem, identifying the type of faults, filling material and the definition of the water table. According to the geological and geotechnical studies carried out, the area where the route was defined, passes through a zone of longitudinal fault to the runway, with strong breaking / fracturing, with presence of voids, intense alteration and with advanced argilization of the rock and with the filling up parts of the faults by organic and compressible soils leachate from other horizons. This geology presents as a geotechnical aggravating agent a medium of high hydraulic load and very low resistance to penetration. For more than 20 years, the region presented constant excessive deformations in the upper layers of the pavement, which after routine services of regularization, reconformation, re-compaction of the layers and application of the asphalt coating. The faults were quickly propagated to the surface of the asphalt pavement, generating a longitudinal shear, forming steps (unevenness), close to 40 cm, causing numerous accidents and discomfort to the drivers, since the geometric positioning was in a horizontal curve. Several projects were presented to the region's highway department to solve the problem. Due to the need for partial closure of the runway, the short time for execution, the use of geosynthetics was proposed and the most adequate solution for the problem was taken into account the movement of existing geological faults and the position of the water level in relation to several Layers of pavement and failure. In order to avoid any flow of water in the body of the landfill and in the filling material of the faults, a drainage curtain solution was used, carried out at 4.0 meters depth, with drainage geo-composite and as reinforcement element and inhibitor of the possible A geogrid of 200 kN / m of resistance was inserted at the base of the reconstituted landfill. Recent evaluations, after 13 years of application of the solution, show the efficiency of the technique used, supported by the geotechnical studies carried out in the area.Keywords: geosynthetics, geocomposite, geogrid, road, recovery, geological failure
Procedia PDF Downloads 167156 Catalytic Pyrolysis of Sewage Sludge for Upgrading Bio-Oil Quality Using Sludge-Based Activated Char as an Alternative to HZSM5
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Due to the concerns about the depletion of fossil fuel sources and the deteriorating environment, the attempt to investigate the production of renewable energy will play a crucial role as a potential to alleviate the dependency on mineral fuels. One particular area of interest is the generation of bio-oil through sewage sludge (SS) pyrolysis. SS can be a potential candidate in contrast to other types of biomasses due to its availability and low cost. However, the presence of high molecular weight hydrocarbons and oxygenated compounds in the SS bio-oil hinders some of its fuel applications. In this context, catalytic pyrolysis is another attainable route to upgrade bio-oil quality. Among different catalysts (i.e., zeolites) studied for SS pyrolysis, activated chars (AC) are eco-friendly alternatives. The beneficial features of AC derived from SS comprise the comparatively large surface area, porosity, enriched surface functional groups, and presence of a high amount of metal species that can improve the catalytic activity. Hence, a sludge-based AC catalyst was fabricated in a single-step pyrolysis reaction with NaOH as the activation agent and was compared with HZSM5 zeolite in this study. The thermal decomposition and kinetics were invested via thermogravimetric analysis (TGA) for guidance and control of pyrolysis and catalytic pyrolysis and the design of the pyrolysis setup. The results indicated that the pyrolysis and catalytic pyrolysis contains four obvious stages, and the main decomposition reaction occurred in the range of 200-600°C. The Coats-Redfern method was applied in the 2nd and 3rd devolatilization stages to estimate the reaction order and activation energy (E) from the mass loss data. The average activation energy (Em) values for the reaction orders n = 1, 2, and 3 were in the range of 6.67-20.37 kJ for SS; 1.51-6.87 kJ for HZSM5; and 2.29-9.17 kJ for AC, respectively. According to the results, AC and HZSM5 both were able to improve the reaction rate of SS pyrolysis by abridging the Em value. Moreover, to generate and examine the effect of the catalysts on the quality of bio-oil, a fixed-bed pyrolysis system was designed and implemented. The composition analysis of the produced bio-oil was carried out via gas chromatography/mass spectrometry (GC/MS). The selected SS to catalyst ratios were 1:1, 2:1, and 4:1. The optimum ratio in terms of cracking the long-chain hydrocarbons and removing oxygen-containing compounds was 1:1 for both catalysts. The upgraded bio-oils with AC and HZSM5 were in the total range of C4-C17, with around 72% in the range of C4-C9. The bio-oil from pyrolysis of SS contained 49.27% oxygenated compounds, while with the presence of AC and HZSM5 dropped to 13.02% and 7.3%, respectively. Meanwhile, the generation of benzene, toluene, and xylene (BTX) compounds was significantly improved in the catalytic process. Furthermore, the fabricated AC catalyst was characterized by BET, SEM-EDX, FT-IR, and TGA techniques. Overall, this research demonstrated AC is an efficient catalyst in the pyrolysis of SS and can be used as a cost-competitive catalyst in contrast to HZSM5.Keywords: catalytic pyrolysis, sewage sludge, activated char, HZSM5, bio-oil
Procedia PDF Downloads 178155 Analysis of Thermal Comfort in Educational Buildings Using Computer Simulation: A Case Study in Federal University of Parana, Brazil
Authors: Ana Julia C. Kfouri
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A prerequisite of any building design is to provide security to the users, taking the climate and its physical and physical-geometrical variables into account. It is also important to highlight the relevance of the right material elements, which arise between the person and the agent, and must provide improved thermal comfort conditions and low environmental impact. Furthermore, technology is constantly advancing, as well as computational simulations for projects, and they should be used to develop sustainable building and to provide higher quality of life for its users. In relation to comfort, the more satisfied the building users are, the better their intellectual performance will be. Based on that, the study of thermal comfort in educational buildings is of relative relevance, since the thermal characteristics in these environments are of vital importance to all users. Moreover, educational buildings are large constructions and when they are poorly planned and executed they have negative impacts to the surrounding environment, as well as to the user satisfaction, throughout its whole life cycle. In this line of thought, to evaluate university classroom conditions, it was accomplished a detailed case study on the thermal comfort situation at Federal University of Parana (UFPR). The main goal of the study is to perform a thermal analysis in three classrooms at UFPR, in order to address the subjective and physical variables that influence thermal comfort inside the classroom. For the assessment of the subjective components, a questionnaire was applied in order to evaluate the reference for the local thermal conditions. Regarding the physical variables, it was carried out on-site measurements, which consist of performing measurements of air temperature and air humidity, both inside and outside the building, as well as meteorological variables, such as wind speed and direction, solar radiation and rainfall, collected from a weather station. Then, a computer simulation based on results from the EnergyPlus software to reproduce air temperature and air humidity values of the three classrooms studied was conducted. The EnergyPlus outputs were analyzed and compared with the on-site measurement results to be possible to come out with a conclusion related to the local thermal conditions. The methodological approach included in the study allowed a distinct perspective in an educational building to better understand the classroom thermal performance, as well as the reason of such behavior. Finally, the study induces a reflection about the importance of thermal comfort for educational buildings and propose thermal alternatives for future projects, as well as a discussion about the significant impact of using computer simulation on engineering solutions, in order to improve the thermal performance of UFPR’s buildings.Keywords: computer simulation, educational buildings, EnergyPlus, humidity, temperature, thermal comfort
Procedia PDF Downloads 383154 Medicinal Plants: An Antiviral Depository with Complex Mode of Action
Authors: Daniel Todorov, Anton Hinkov, Petya Angelova, Kalina Shishkova, Venelin Tsvetkov, Stoyan Shishkov
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Human herpes viruses (HHV) are ubiquitous pathogens with a pandemic spread across the globe. HHV type 1 is the main causative agent of cold sores and fever blisters around the mouth and on the face, whereas HHV type 2 is generally responsible for genital herpes outbreaks. The treatment of both viruses is more or less successful with antivirals from the nucleoside analogues group. Their wide application increasingly leads to the emergence of resistant mutants In the past, medicinal plants have been used to treat a number of infectious and non-infectious diseases. Their diversity and ability to produce the vast variety of secondary metabolites according to the characteristics of the environment give them the potential to help us in our warfare with viral infections. The variable chemical characteristics and complex composition is an advantage in the treatment of herpes since the emergence of resistant mutants is significantly complicated. The screening process is difficult due to the lack of standardization. That is why it is especially important to follow the mechanism of antiviral action of plants. On the one hand, it may be expected to interact with its compounds, resulting in enhanced antiviral effects, and the most appropriate environmental conditions can be chosen to maximize the amount of active secondary metabolites. During our study, we followed the activity of various plant extracts on the viral replication cycle as well as their effect on the extracellular virion. We obtained our results following the logical sequence of the experimental settings - determining the cytotoxicity of the extracts, evaluating the overall effect on viral replication and extracellular virion.During our research, we have screened a variety of plant extracts for their antiviral activity against both virus replication and the virion itself. We investigated the effect of the extracts on the individual stages of the viral replication cycle - viral adsorption, penetration and the effect on replication depending on the time of addition. If there are positive results in the later experiments, we had studied the activity over viral adsorption, penetration and the effect of replication according to the time of addition. Our results indicate that some of the extracts from the Lamium album have several targets. The first stages of the viral life cycle are most affected. Several of our active antiviral agents have shown an effect on extracellular virion and adsorption and penetration processes. Our research over the last decade has shown several curative antiviral plants - some of which are from the Lamiacea family. The rich set of active ingredients of the plants in this family makes them a good source of antiviral preparation.Keywords: human herpes virus, antiviral activity, Lamium album, Nepeta nuda
Procedia PDF Downloads 153153 Characteristics of Wood Plastics Nano-Composites Made of Agricultural Residues and Urban Recycled Polymer Materials
Authors: Amir Nourbakhsh Habibabadi, Alireza Ashori
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Context: The growing concern over the management of plastic waste and the high demand for wood-based products have led to the development of wood-plastic composites. Agricultural residues, which are abundantly available, can be used as a source of lignocellulosic fibers in the production of these composites. The use of recycled polymers and nanomaterials is also a promising approach to enhance the mechanical and physical properties of the composites. Research Aim: The aim of this study was to investigate the feasibility of using recycled high-density polyethylene (rHDPE), polypropylene (rPP), and agricultural residues fibers for manufacturing wood-plastic nano-composites. The effects of these materials on the mechanical properties of the composites, specifically tensile and flexural strength, were studied. Methodology: The study utilized an experimental approach where extruders and hot presses were used to fabricate the composites. Five types of cellulosic residues fibers (bagasse, corn stalk, rice straw, sunflower, and canola stem), three levels of nanomaterials (carbon nanotubes, nano silica, and nanoclay), and coupling agent were used to chemically bind the wood/polymer fibers, chemicals, and reinforcement. The mechanical properties of the composites were then analyzed. Findings: The study found that composites made with rHDPE provided moderately superior tensile and flexural properties compared to rPP samples. The addition of agricultural residues in several types of wood-plastic nano-composites significantly improved their bending and tensile properties, with bagasse having the most significant advantage over other lignocellulosic materials. The use of recycled polymers, agricultural residues, and nano-silica resulted in composites with the best strength properties. Theoretical Importance: The study's findings suggest that using agricultural fiber residues as reinforcement in wood/plastic nanocomposites is a viable approach to improve the mechanical properties of the composites. Additionally, the study highlights the potential of using recycled polymers in the development of value-added products without compromising the product's properties. Data Collection and Analysis Procedures: The study collected data on the mechanical properties of the composites using tensile and flexural tests. Statistical analyses were performed to determine the significant effects of the various materials used. Question addressed: Can agricultural residues and recycled polymers be used to manufacture wood-plastic nano-composites with enhanced mechanical properties? Conclusion: The study demonstrates the feasibility of using agricultural residues and recycled polymers in the production of wood-plastic nano-composites. The addition of these materials significantly improved the mechanical properties of the composites, with bagasse being the most effective agricultural residue. The study's findings suggest that composites made from recycled materials can offer value-added products without sacrificing performance.Keywords: polymer, composites, wood, nano
Procedia PDF Downloads 68152 Sustainable Antimicrobial Biopolymeric Food & Biomedical Film Engineering Using Bioactive AMP-Ag+ Formulations
Authors: Eduardo Lanzagorta Garcia, Chaitra Venkatesh, Romina Pezzoli, Laura Gabriela Rodriguez Barroso, Declan Devine, Margaret E. Brennan Fournet
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New antimicrobial interventions are urgently required to combat rising global health and medical infection challenges. Here, an innovative antimicrobial technology, providing price competitive alternatives to antibiotics and readily integratable with currently technological systems is presented. Two cutting edge antimicrobial materials, antimicrobial peptides (AMPs) and uncompromised sustained Ag+ action from triangular silver nanoplates (TSNPs) reservoirs, are merged for versatile effective antimicrobial action where current approaches fail. Antimicrobial peptides (AMPs) exist widely in nature and have recently been demonstrated for broad spectrum of activity against bacteria, viruses, and fungi. TSNP’s are highly discrete, homogenous and readily functionisable Ag+ nanoreseviors that have a proven amenability for operation within in a wide range of bio-based settings. In a design for advanced antimicrobial sustainable plastics, antimicrobial TSNPs are formulated for processing within biodegradable biopolymers. Histone H5 AMP was selected for its reported strong antimicrobial action and functionalized with the TSNP (AMP-TSNP) in a similar fashion to previously reported TSNP biofunctionalisation methods. A synergy between the propensity of biopolymers for degradation and Ag+ release combined with AMP activity provides a novel mechanism for the sustained antimicrobial action of biopolymeric thin films. Nanoplates are transferred from aqueous phase to an organic solvent in order to facilitate integration within hydrophobic polymers. Extrusion is used in combination with calendering rolls to create thin polymerc film where the nanoplates are embedded onto the surface. The resultant antibacterial functional films are suitable to be adapted for food packing and biomedical applications. TSNP synthesis were synthesized by adapting a previously reported seed mediated approach. TSNP synthesis was scaled up for litre scale batch production and subsequently concentrated to 43 ppm using thermally controlled H2O removal. Nanoplates were transferred from aqueous phase to an organic solvent in order to facilitate integration within hydrophobic polymers. This was acomplised by functionalizing the TSNP with thiol terminated polyethylene glycol and using centrifugal force to transfer them to chloroform. Polycaprolactone (PCL) and Polylactic acid (PLA) were individually processed through extrusion, TSNP and AMP-TSNP solutions were sprayed onto the polymer immediately after exiting the dye. Calendering rolls were used to disperse and incorporate TSNP and TSNP-AMP onto the surface of the extruded films. Observation of the characteristic blue colour confirms the integrity of the TSNP within the films. Antimicrobial tests were performed by incubating Gram + and Gram – strains with treated and non-treated films, to evaluate if bacterial growth was reduced due to the presence of the TSNP. The resulting films successfully incorporated TSNP and AMP-TSNP. Reduced bacterial growth was observed for both Gram + and Gram – strains for both TSNP and AMP-TSNP compared with untreated films indicating antimicrobial action. The largest growth reduction was observed for AMP-TSNP treated films demonstrating the additional antimicrobial activity due to the presence of the AMPs. The potential of this technology to impede bacterial activity in food industry and medical surfaces will forge new confidence in the battle against antibiotic resistant bacteria, serving to greatly inhibit infections and facilitate patient recovery.Keywords: antimicrobial, biodegradable, peptide, polymer, nanoparticle
Procedia PDF Downloads 115151 Using Lysosomal Immunogenic Cell Death to Target Breast Cancer via Xanthine Oxidase/Micro-Antibody Fusion Protein
Authors: Iulianna Taritsa, Kuldeep Neote, Eric Fossel
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Lysosome-induced immunogenic cell death (LIICD) is a powerful mechanism of targeting cancer cells that kills circulating malignant cells and primes the host’s immune cells against future remission. Current immunotherapies for cancer are limited in preventing recurrence – a gap that can be bridged by training the immune system to recognize cancer neoantigens. Lysosomal leakage can be induced therapeutically to traffic antigens from dying cells to dendritic cells, which can later present those tumorigenic antigens to T cells. Previous research has shown that oxidative agents administered in the tumor microenvironment can initiate LIICD. We generated a fusion protein between an oxidative agent known as xanthine oxidase (XO) and a mini-antibody specific for EGFR/HER2-sensitive breast tumor cells. The anti-EGFR single domain antibody fragment is uniquely sourced from llama, which is functional without the presence of a light chain. These llama micro-antibodies have been shown to be better able to penetrate tissues and have improved physicochemical stability as compared to traditional monoclonal antibodies. We demonstrate that the fusion protein created is stable and can induce early markers of immunogenic cell death in an in vitro human breast cancer cell line (SkBr3). Specifically, we measured overall cell death, as well as surface-expressed calreticulin, extracellular ATP release, and HMGB1 production. These markers are consensus indicators of ICD. Flow cytometry, luminescence assays, and ELISA were used respectively to quantify biomarker levels between treated versus untreated cells. We also included a positive control group of SkBr3 cells dosed with doxorubicin (a known inducer of LIICD) and a negative control dosed with cisplatin (a known inducer of cell death, but not of the immunogenic variety). We looked at each marker at various time points after cancer cells were treated with the XO/antibody fusion protein, doxorubicin, and cisplatin. Upregulated biomarkers after treatment with the fusion protein indicate an immunogenic response. We thus show the potential for this fusion protein to induce an anticancer effect paired with an adaptive immune response against EGFR/HER2+ cells. Our research in human cell lines here provides evidence for the success of the same therapeutic method for patients and serves as the gateway to developing a new treatment approach against breast cancer.Keywords: apoptosis, breast cancer, immunogenic cell death, lysosome
Procedia PDF Downloads 198150 Revealing the Nitrogen Reaction Pathway for the Catalytic Oxidative Denitrification of Fuels
Authors: Michael Huber, Maximilian J. Poller, Jens Tochtermann, Wolfgang Korth, Andreas Jess, Jakob Albert
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Aside from the desulfurisation, the denitrogenation of fuels is of great importance to minimize the environmental impact of transport emissions. The oxidative reaction pathway of organic nitrogen in the catalytic oxidative denitrogenation could be successfully elucidated. This is the first time such a pathway could be traced in detail in non-microbial systems. It was found that the organic nitrogen is first oxidized to nitrate, which is subsequently reduced to molecular nitrogen via nitrous oxide. Hereby, the organic substrate serves as a reducing agent. The discovery of this pathway is an important milestone for the further development of fuel denitrogenation technologies. The United Nations aims to counteract global warming with Net Zero Emissions (NZE) commitments; however, it is not yet foreseeable when crude oil-based fuels will become obsolete. In 2021, more than 50 million barrels per day (mb/d) were consumed for the transport sector alone. Above all, heteroatoms such as sulfur or nitrogen produce SO₂ and NOx during combustion in the engines, which is not only harmful to the climate but also to health. Therefore, in refineries, these heteroatoms are removed by hy-drotreating to produce clean fuels. However, this catalytic reaction is inhibited by the basic, nitrogenous reactants (e.g., quinoline) as well as by NH3. The ion pair of the nitrogen atom forms strong pi-bonds to the active sites of the hydrotreating catalyst, which dimin-ishes its activity. To maximize the desulfurization and denitrogenation effectiveness in comparison to just extraction and adsorption, selective oxidation is typically combined with either extraction or selective adsorption. The selective oxidation produces more polar compounds that can be removed from the non-polar oil in a separate step. The extraction step can also be carried out in parallel to the oxidation reaction, as a result of in situ separation of the oxidation products (ECODS; extractive catalytic oxidative desulfurization). In this process, H8PV5Mo7O40 (HPA-5) is employed as a homogeneous polyoxometalate (POM) catalyst in an aqueous phase, whereas the sulfur containing fuel components are oxidized after diffusion from the organic fuel phase into the aqueous catalyst phase, to form highly polar products such as H₂SO₄ and carboxylic acids, which are thereby extracted from the organic fuel phase and accumulate in the aqueous phase. In contrast to the inhibiting properties of the basic nitrogen compounds in hydrotreating, the oxidative desulfurization improves with simultaneous denitrification in this system (ECODN; extractive catalytic oxidative denitrogenation). The reaction pathway of ECODS has already been well studied. In contrast, the oxidation of nitrogen compounds in ECODN is not yet well understood and requires more detailed investigations.Keywords: oxidative reaction pathway, denitrogenation of fuels, molecular catalysis, polyoxometalate
Procedia PDF Downloads 178149 Brazilian Transmission System Efficient Contracting: Regulatory Impact Analysis of Economic Incentives
Authors: Thelma Maria Melo Pinheiro, Guilherme Raposo Diniz Vieira, Sidney Matos da Silva, Leonardo Mendonça de Oliveira Queiroz, Mateus Sousa Pinheiro, Danyllo Wenceslau de Oliveira Lopes
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The present article has the objective to describe the regulatory impact analysis (RIA) of the contracting efficiency of the Brazilian transmission system usage. This contracting is made by users connected to the main transmission network and is used to guide necessary investments to supply the electrical energy demand. Therefore, an inefficient contracting of this energy amount distorts the real need for grid capacity, affecting the sector planning accuracy and resources optimization. In order to provide this efficiency, the Brazilian Electricity Regulatory Agency (ANEEL) homologated the Normative Resolution (NR) No. 666, from July 23th of 2015, which consolidated the procedures for the contracting of transmission system usage and the contracting efficiency verification. Aiming for a more efficient and rational transmission system contracting, the resolution established economic incentives denominated as Inefficiency installment for excess (IIE) and inefficiency installment for over-contracting (IIOC). The first one, IIE, is verified when the contracted demand exceeds the established regulatory limit; it is applied to consumer units, generators, and distribution companies. The second one, IIOC, is verified when the distributors over-contract their demand. Thus, the establishment of the inefficiency installments IIE and IIOC intends to avoid the agent contract less energy than necessary or more than it is needed. Knowing that RIA evaluates a regulatory intervention to verify if its goals were achieved, the results from the application of the above-mentioned normative resolution to the Brazilian transmission sector were analyzed through indicators that were created for this RIA to evaluate the contracting efficiency transmission system usage, using real data from before and after the homologation of the normative resolution in 2015. For this, indicators were used as the efficiency contracting indicator (ECI), excess of demand indicator (EDI), and over-contracting of demand indicator (ODI). The results demonstrated, through the ECI analysis, a decrease of the contracting efficiency, a behaviour that was happening even before the normative resolution of 2015. On the other side, the EDI showed a considerable decrease in the amount of excess for the distributors and a small reduction for the generators; moreover, the ODI notable decreased, which optimizes the usage of the transmission installations. Hence, with the complete evaluation from the data and indicators, it was possible to conclude that IIE is a relevant incentive for a more efficient contracting, indicating to the agents that their contracting values are not adequate to keep their service provisions for their users. The IIOC also has its relevance, to the point that it shows to the distributors that their contracting values are overestimated.Keywords: contracting, electricity regulation, evaluation, regulatory impact analysis, transmission power system
Procedia PDF Downloads 118148 Immunomodulatory Role of Heat Killed Mycobacterium indicus pranii against Cervical Cancer
Authors: Priyanka Bhowmik, Subrata Majumdar, Debprasad Chattopadhyay
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Background: Cervical cancer is the third major cause of cancer in women and the second most frequent cause of cancer related deaths causing 300,000 deaths annually worldwide. Evasion of immune response by Human Papilloma Virus (HPV), the key contributing factor behind cancer and pre-cancerous lesions of the uterine cervix, makes immunotherapy a necessity to treat this disease. Objective: A Heat killed fraction of Mycobacterium indicus pranii (MIP), a non-pathogenic Mycobacterium has been shown to exhibit cytotoxic effects on different cancer cells, including human cervical carcinoma cell line HeLa. However, the underlying mechanisms remain unknown. The aim of this study is to decipher the mechanism of MIP induced HeLa cell death. Methods: The cytotoxicity of Mycobacterium indicus pranii against HeLa cells was evaluated by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Apoptosis was detected by annexin V and Propidium iodide (PI) staining. The assessment of reactive oxygen species (ROS) generation and cell cycle analysis were measured by flow cytometry. The expression of apoptosis associated genes was analyzed by real time PCR. Result: MIP could inhibit the proliferation of HeLa cell in a time and dose dependent manner but caused minor damage to normal cells. The induction of apoptosis was confirmed by the cell surface presentation of phosphatidyl serine, DNA fragmentation, and mitochondrial damage. MIP caused very early (as early as 30 minutes) transcriptional activation of p53, followed by a higher activation (32 fold) at 24 hours suggesting prime importance of p53 in MIP-induced apoptosis in HeLa cell. The up regulation of p53 dependent pro-apoptotic genes Bax, Bak, PUMA, and Noxa followed a lag phase that was required for the transcriptional p53 program. MIP also caused the transcriptional up regulation of Toll like receptor 2 and 4 after 30 minutes of MIP treatment suggesting recognition of MIP by toll like receptors. Moreover, MIP caused the inhibition of expression of HPV anti apoptotic gene E6, which is known to interfere with p53/PUMA/Bax apoptotic cascade. This inhibition might have played a role in transcriptional up regulation of PUMA and subsequently apoptosis. ROS was generated transiently which was concomitant with the highest transcription activation of p53 suggesting a plausible feedback loop network of p53 and ROS in the apoptosis of HeLa cells. Scavenger of ROS, such as N-acetyl-L-cysteine, decreased apoptosis suggesting ROS is an important effector of MIP induced apoptosis. Conclusion: Taken together, MIP possesses full potential to be a novel therapeutic agent in the clinical treatment of cervical cancer.Keywords: cancer, mycobacterium, immunity, immunotherapy.
Procedia PDF Downloads 248147 Functional Finishing of Organic Cotton Fabric Using Vetiver Root Extract
Authors: Sakeena Naikwadi, K. Jagaluraiah Sannapapamma
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Vetiveria zizanioides is an aromatic grass and traditionally been used in aromatherapy and ayurvedic medicine. Vetiver root is multi-functional biopolymer and has highly aromatic, antimicrobial, UV blocking, antioxidant properties suitable for textile finishing. The vetiver root (Gulabi) powder of different concentration (2, 4, 6,8 percent) were extracted by aqueous and solvent methods subjected to bioassay for antimicrobial efficiency and GCMS spectral analysis. The organic cotton fabric was finished with vetiver root extract (8 percent) by exhaust and pad dry cure methods. The finished fabric was assessed for functional properties viz., UV protective factor, antimicrobial efficiency and aroma intensity. The results revealed that Ethanol extraction showed a greater zone of inhibition compared to aqueous extract in root powder. Among the concentrations, 8 percent root extract in ethanol showed a greater zone of inhibition against gram-positive organism S. aureus and gram-negative organism E. coli. The major compounds present in vetiver root extracts were diethyl pathalate with greater percentage (87.73 %) followed by 7- Isopropyl dimethyl carboxylic acid (4.05 %), 2-butanone 4-trimethyle cyclohexen (1.21 %), phenanthrene carboxylic acid (1.03 %), naphthalene pentanoic acid (0.99 %), 1-phenanthrene carboxylic acid and 1 cyclohexenone 2-methyl oxobuty (0.89 %). The sample finished by pad dry cure method exhibited better UV protection even after 10th wash as compared to exhaust method. Vetiver extract treated samples exhibited maximum zone of inhibition against S. aureus than the E. coli organism. The vetiver root extract treated organic cotton fabric through pad dry cure method possessed good antimicrobial activity against S. aureus and E. coli even after 20th washes compared to vetiver root extract treated by exhaust method. The olfactory analysis was carried out by 30 panels of members and opined that vetiver root extract treated fabric has very good and pleasant aroma with better tactile properties that provide cooling, soothing effect and enhances the mood of the wearer. Vetiver root extract finished organic cotton fabric possessed aroma, antimicrobial and UV properties which are aptly suitable for medical and healthcare textiles viz., wound dressing, bandage gauze, surgical cloths, baby diapers and sanitary napkins. It can be used as after finishing agent for variegated garments and made-ups and can be replaced with commercial after finishing agents.Keywords: antimicrobial, olfactory analysis, UV protection factor, vetiver root extract
Procedia PDF Downloads 235146 Lipid-Coated Magnetic Nanoparticles for Frequency Triggered Drug Delivery
Authors: Yogita Patil-Sen
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Superparamagnetic Iron Oxide Nanoparticles (SPIONs) have become increasingly important materials for separation of specific bio-molecules, drug delivery vehicle, contrast agent for MRI and magnetic hyperthermia for cancer therapy. Hyperthermia is emerging as an alternative cancer treatment to the conventional radio- and chemo-therapy, which have harmful side effects. When subjected to an alternating magnetic field, the magnetic energy of SPIONs is converted into thermal energy due to movement of particles. The ability of SPIONs to generate heat and potentially kill cancerous cells, which are more susceptible than the normal cells to temperatures higher than 41 °C forms the basis of hyerpthermia treatement. The amount of heat generated depends upon the magnetic properties of SPIONs which in turn is affected by their properties such as size and shape. One of the main problems associated with SPIONs is particle aggregation which limits their employability in in vivo drug delivery applications and hyperthermia cancer treatments. Coating the iron oxide core with thermally responsive lipid based nanostructures tend to overcome the issue of aggregation as well as improve biocompatibility and can enhance drug loading efficiency. Herein we report suitability of SPIONs and silica coated core-shell SPIONs, which are further, coated with various lipids for drug delivery and magnetic hyperthermia applications. The synthesis of nanoparticles is carried out using the established methods reported in the literature with some modifications. The nanoparticles are characterised using Infrared spectroscopy (IR), X-ray Diffraction (XRD), Scanning Electron Microscopy (SEM), Transmission Electron Microscopy (TEM) and Vibrating Sample Magnetometer (VSM). The heating ability of nanoparticles is tested under alternating magnetic field. The efficacy of the nanoparticles as drug carrier is also investigated. The loading of an anticancer drug, Doxorubicin at 18 °C is measured up to 48 hours using UV-visible spectrophotometer. The drug release profile is obtained under thermal incubation condition at 37 °C and compared with that under the influence of alternating magnetic field. The results suggest that the nanoparticles exhibit superparamagnetic behaviour, although coating reduces the magnetic properties of the particles. Both the uncoated and coated particles show good heating ability, again it is observed that coating decreases the heating behaviour of the particles. However, coated particles show higher drug loading efficiency than the uncoated particles and the drug release is much more controlled under the alternating magnetic field. Thus, the results demonstrate that lipid coated SPIONs exhibit potential as drug delivery vehicles for magnetic hyperthermia based cancer therapy.Keywords: drug delivery, hyperthermia, lipids, superparamagnetic iron oxide nanoparticles (SPIONS)
Procedia PDF Downloads 231145 Learning to Translate by Learning to Communicate to an Entailment Classifier
Authors: Szymon Rutkowski, Tomasz Korbak
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We present a reinforcement-learning-based method of training neural machine translation models without parallel corpora. The standard encoder-decoder approach to machine translation suffers from two problems we aim to address. First, it needs parallel corpora, which are scarce, especially for low-resource languages. Second, it lacks psychological plausibility of learning procedure: learning a foreign language is about learning to communicate useful information, not merely learning to transduce from one language’s 'encoding' to another. We instead pose the problem of learning to translate as learning a policy in a communication game between two agents: the translator and the classifier. The classifier is trained beforehand on a natural language inference task (determining the entailment relation between a premise and a hypothesis) in the target language. The translator produces a sequence of actions that correspond to generating translations of both the hypothesis and premise, which are then passed to the classifier. The translator is rewarded for classifier’s performance on determining entailment between sentences translated by the translator to disciple’s native language. Translator’s performance thus reflects its ability to communicate useful information to the classifier. In effect, we train a machine translation model without the need for parallel corpora altogether. While similar reinforcement learning formulations for zero-shot translation were proposed before, there is a number of improvements we introduce. While prior research aimed at grounding the translation task in the physical world by evaluating agents on an image captioning task, we found that using a linguistic task is more sample-efficient. Natural language inference (also known as recognizing textual entailment) captures semantic properties of sentence pairs that are poorly correlated with semantic similarity, thus enforcing basic understanding of the role played by compositionality. It has been shown that models trained recognizing textual entailment produce high-quality general-purpose sentence embeddings transferrable to other tasks. We use stanford natural language inference (SNLI) dataset as well as its analogous datasets for French (XNLI) and Polish (CDSCorpus). Textual entailment corpora can be obtained relatively easily for any language, which makes our approach more extensible to low-resource languages than traditional approaches based on parallel corpora. We evaluated a number of reinforcement learning algorithms (including policy gradients and actor-critic) to solve the problem of translator’s policy optimization and found that our attempts yield some promising improvements over previous approaches to reinforcement-learning based zero-shot machine translation.Keywords: agent-based language learning, low-resource translation, natural language inference, neural machine translation, reinforcement learning
Procedia PDF Downloads 127144 Building an Opinion Dynamics Model from Experimental Data
Authors: Dino Carpentras, Paul J. Maher, Caoimhe O'Reilly, Michael Quayle
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Opinion dynamics is a sub-field of agent-based modeling that focuses on people’s opinions and their evolutions over time. Despite the rapid increase in the number of publications in this field, it is still not clear how to apply these models to real-world scenarios. Indeed, there is no agreement on how people update their opinion while interacting. Furthermore, it is not clear if different topics will show the same dynamics (e.g., more polarized topics may behave differently). These problems are mostly due to the lack of experimental validation of the models. Some previous studies started bridging this gap in the literature by directly measuring people’s opinions before and after the interaction. However, these experiments force people to express their opinion as a number instead of using natural language (and then, eventually, encoding it as numbers). This is not the way people normally interact, and it may strongly alter the measured dynamics. Another limitation of these studies is that they usually average all the topics together, without checking if different topics may show different dynamics. In our work, we collected data from 200 participants on 5 unpolarized topics. Participants expressed their opinions in natural language (“agree” or “disagree”). We also measured the certainty of their answer, expressed as a number between 1 and 10. However, this value was not shown to other participants to keep the interaction based on natural language. We then showed the opinion (and not the certainty) of another participant and, after a distraction task, we repeated the measurement. To make the data compatible with opinion dynamics models, we multiplied opinion and certainty to obtain a new parameter (here called “continuous opinion”) ranging from -10 to +10 (using agree=1 and disagree=-1). We firstly checked the 5 topics individually, finding that all of them behaved in a similar way despite having different initial opinions distributions. This suggested that the same model could be applied for different unpolarized topics. We also observed that people tend to maintain similar levels of certainty, even when they changed their opinion. This is a strong violation of what is suggested from common models, where people starting at, for example, +8, will first move towards 0 instead of directly jumping to -8. We also observed social influence, meaning that people exposed with “agree” were more likely to move to higher levels of continuous opinion, while people exposed with “disagree” were more likely to move to lower levels. However, we also observed that the effect of influence was smaller than the effect of random fluctuations. Also, this configuration is different from standard models, where noise, when present, is usually much smaller than the effect of social influence. Starting from this, we built an opinion dynamics model that explains more than 80% of data variance. This model was also able to show the natural conversion of polarization from unpolarized states. This experimental approach offers a new way to build models grounded on experimental data. Furthermore, the model offers new insight into the fundamental terms of opinion dynamics models.Keywords: experimental validation, micro-dynamics rule, opinion dynamics, update rule
Procedia PDF Downloads 108143 Development of a Quick On-Site Pass/Fail Test for the Evaluation of Fresh Concrete Destined for Application as Exposed Concrete
Authors: Laura Kupers, Julie Piérard, Niki Cauberg
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The use of exposed concrete (sometimes referred to as architectural concrete), keeps gaining popularity. Exposed concrete has the advantage to combine the structural properties of concrete with an aesthetic finish. However, for a successful aesthetic finish, much attention needs to be paid to the execution (formwork, release agent, curing, weather conditions…), the concrete composition (choice of the raw materials and mix proportions) as well as to its fresh properties. For the latter, a simple on-site pass/fail test could halt the casting of concrete not suitable for architectural concrete and thus avoid expensive repairs later. When architects opt for an exposed concrete, they usually want a smooth, uniform and nearly blemish-free surface. For this choice, a standard ‘construction’ concrete does not suffice. An aesthetic surface finishing requires the concrete to contain a minimum content of fines to minimize the risk of segregation and to allow complete filling of more complex shaped formworks. The concrete may neither be too viscous as this makes it more difficult to compact and it increases the risk of blow holes blemishing the surface. On the other hand, too much bleeding may cause color differences on the concrete surface. An easy pass/fail test, which can be performed on the site just before the casting, could avoid these problems. In case the fresh concrete fails the test, the concrete can be rejected. Only in case the fresh concrete passes the test, the concrete would be cast. The pass/fail tests are intended for a concrete with a consistency class S4. Five tests were selected as possible onsite pass/fail test. Two of these tests already exist: the K-slump test (ASTM C1362) and the Bauer Filter Press Test. The remaining three tests were developed by the BBRI in order to test the segregation resistance of fresh concrete on site: the ‘dynamic sieve stability test’, the ‘inverted cone test’ and an adapted ‘visual stability index’ (VSI) for the slump and flow test. These tests were inspired by existing tests for self-compacting concrete, for which the segregation resistance is of great importance. The suitability of the fresh concrete mixtures was also tested by means of a laboratory reference test (resistance to segregation) and by visual inspection (blow holes, structure…) of small test walls. More than fifteen concrete mixtures of different quality were tested. The results of the pass/fail tests were compared with the results of this laboratory reference test and the test walls. The preliminary laboratory results indicate that concrete mixtures ‘suitable’ for placing as exposed concrete (containing sufficient fines, a balanced grading curve etc.) can be distinguished from ‘inferior’ concrete mixtures. Additional laboratory tests, as well as tests on site, will be conducted to confirm these preliminary results and to set appropriate pass/fail values.Keywords: exposed concrete, testing fresh concrete, segregation resistance, bleeding, consistency
Procedia PDF Downloads 423142 Poly(Acrylamide-Co-Itaconic Acid) Nanocomposite Hydrogels and Its Use in the Removal of Lead in Aqueous Solution
Authors: Majid Farsadrouh Rashti, Alireza Mohammadinejad, Amir Shafiee Kisomi
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Lead (Pb²⁺), a cation, is a prime constituent of the majority of the industrial effluents such as mining, smelting and coal combustion, Pb-based painting and Pb containing pipes in water supply systems, paper and pulp refineries, printing, paints and pigments, explosive manufacturing, storage batteries, alloy and steel industries. The maximum permissible limit of lead in the water used for drinking and domesticating purpose is 0.01 mg/L as advised by Bureau of Indian Standards, BIS. This becomes the acceptable 'safe' level of lead(II) ions in water beyond which, the water becomes unfit for human use and consumption, and is potential enough to lead health problems and epidemics leading to kidney failure, neuronal disorders, and reproductive infertility. Superabsorbent hydrogels are loosely crosslinked hydrophilic polymers that in contact with aqueous solution can easily water and swell to several times to their initial volume without dissolving in aqueous medium. Superabsorbents are kind of hydrogels capable to swell and absorb a large amount of water in their three-dimensional networks. While the shapes of hydrogels do not change extensively during swelling, because of tremendously swelling capacity of superabsorbent, their shape will broadly change.Because of their superb response to changing environmental conditions including temperature pH, and solvent composition, superabsorbents have been attracting in numerous industrial applications. For instance, water retention property and subsequently. Natural-based superabsorbent hydrogels have attracted much attention in medical pharmaceutical, baby diapers, agriculture, and horticulture because of their non-toxicity, biocompatibility, and biodegradability. Novel superabsorbent hydrogel nanocomposites were prepared by graft copolymerization of acrylamide and itaconic acid in the presence of nanoclay (laponite), using methylene bisacrylamide (MBA) and potassium persulfate, former as a crosslinking agent and the second as an initiator. The superabsorbent hydrogel nanocomposites structure was characterized by FTIR spectroscopy, SEM and TGA Spectroscopy adsorption of metal ions on poly (AAm-co-IA). The equilibrium swelling values of copolymer was determined by gravimetric method. During the adsorption of metal ions on polymer, residual metal ion concentration in the solution and the solution pH were measured. The effects of the clay content of the hydrogel on its metal ions uptake behavior were studied. The NC hydrogels may be considered as a good candidate for environmental applications to retain more water and to remove heavy metals.Keywords: adsorption, hydrogel, nanocomposite, super adsorbent
Procedia PDF Downloads 187141 Impact of the Achyranthes aspera (Amaranthaceae) Extracts on the Survival and Histological Architecture of the Midgut Epithelial Tissue of Early Fourth Instars of Aedes aegypti (Diptera: Culicidae)
Authors: Aarti Sharma, Sarita Kumar, Pushplata Tripathi
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Aedes aegypti L. is one of the most important insect vectors in the world transmitting several diseases of concern; dengue fever, dengue haemorrhagic fever and yellow fever. Though since ages the control of dengue vector is primarily relied upon the use of synthetic chemical insecticides, the continued and indiscriminate use of insecticides for their control has received wide public apprehension because of multifarious problems including insecticide resistance, resurgence of pest species, environmental pollution, toxic hazards to humans and non-target organisms. These problems have necessitated the need to explore and develop alternative strategies using eco-friendly and bio-degradable plant products. Bio-insecticides, despite being the focus of research nowadays, have not been investigated much regarding their physiological effects on the mosquitoes. Thus, the present studies were carried out to investigate the anti-mosquito potential of the leaf and stem hexane extracts of Achyranthes aspera against early fourth instars of Aedes aegypti L and their effects on the histological architecture of their midgut. The larvicidal bioassays conducted with the A. aspera leaf hexane extracts revealed the respective LC30, LC50 and LC90 values of 66.545 ppm, 82.555 ppm, 139.817 ppm while the assays with stem hexane extracts resulted in respective values of 54.982 ppm, 68.133 ppm, 115.075 ppm. The studies clearly indicate the efficacy of extracts as larvicidal agents against Ae. aegypti, the stem extracts being found more effective than the leaf extracts. When the larvae assayed with extracts were investigated for the modifications in the histo-architecture of the midgut, the studies showed significant damage, shrinkage, distortion and vacuolization of gut tissues and peritrophic membrane causing disintegration of epithelial cells and cytoplasmic organelles; extent of toxicity and damage varied depending upon the concentration and exposure time period. These changes revealed appreciable stomach poison potential of A. aspera extracts against Ae. aegypti larvae, which may have also caused adverse impact on the growth and development of larvae. These effects were also found to be more pronounced with the stem extract than the leaf extract. Our findings may prove significant suggesting the use of A. aspera extract as a bio-insecticide against early fourth instar larvae of Ae. aegypti. Further studies are needed to identify the bioactive component in the extracts and to ascertain the use of component in the fields as anti-mosquito control agent.Keywords: Achyranthes aspera, Aedes aegypti, histological architecture, larvicidal, midgut, stomach poison
Procedia PDF Downloads 296140 L. rhamnosus GG Lysate Can Inhibit Cytotoxic Effects of S. aureus on Keratinocytes in vitro
Authors: W. Mohammed Saeed, A. J. Mcbain, S. M. Cruickshank, C. A. O’Neill
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In the gut, probiotics have been shown to protect epithelial cells from pathogenic bacteria through a number of mechanisms: 1-Increasing epithelial barrier function, 2-Modulation of the immune response especially innate immune response, 3-Inhibition of pathogen adherence and down regulation of virulence factors. Since probiotics have positive impacts on the gut, their potential effects on other body tissues, such as skin have begun to be investigated. The purpose of this project is to characterize the potential of probiotic bacteria lysate as therapeutic agent for preventing or reducing the S. aureus infection. Normal human primary keratinocytes (KCs) were exposed to S. aureus (106/ml) in the presence or absence of L. rhamnosus GG lysate (extracted from 108cfu/ml). The viability of the KCs was measured after 24 hours using a trypan blue exclusion assay. When KCs were treated with S aureus alone, only 25% of the KCs remained viable at 24 hours post infection. However, in the presence of L. rhamnosus GG lysate the viability of pathogen infected KCs increased to 58% (p=0.008, n=3). Furthermore, when KCs co-exposed, pre- exposed or post-exposed to L. rhamnosus GG lysate, the viability of the KCs increased to ≈60%, the L. rhamnosus GG lysate was afforded equal protection in different conditions. These data suggests that two possible separate mechanisms are involved in the protective effects of L. rhamnosus GG such as reducing S. aureus growth, or inhibiting of pathogenic adhesion. Interestingly, a lysate of L rhamnosus GG provided significant reduction in S. aureus growth and adhesion of S. aureus that being viable following 24 hours incubation with S aureus. Therefore, a series of Liquid Chromatography (RP-LC) methods were adopted to partially purify the lysate in combination with functional assays to elucidate in which fractions the efficacious molecules were contained. In addition, the Mass Spectrometry-based protein sequencing was used to identify putative proteins in the fractions. The data presented from purification process demonstrated that L. rhamnosus GG lysate has the potential to protect keratinocytes from the toxic effects of the skin pathogen, S. aureus. Three potential mechanisms were identified: inhibition of pathogen growth; competitive exclusion; and displacement of the pathogen from keratinocyte binding sites. In this study, ‘moonlight’ proteins were identified in the current study’s MS/MS data for L. rhamnosus GG lysate, which could elucidate the ability of lysate in the competitive exclusion and displacement of S. aureus from keratinocyte binding sites. Taken together, it can be speculated that L. rhamnosus GG lysate utilizes different mechanisms to protect keratinocytes from S. aureus toxicity. The present study indicates that the proteinaceous substances are involved in anti-adhesion activity. This is achieved by displacing the pathogen and preventing the severity of pathogen infection and the moonlight proteins might be involved in inhibiting the adhesion of pathogens.Keywords: lysate, fractions, adhesion, L. rhamnosus GG, S. aureus toxicity
Procedia PDF Downloads 291139 Strategic Entrepreneurship: Model Proposal for Post-Troika Sustainable Cultural Organizations
Authors: Maria Inês Pinho
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Recent literature on issues of Cultural Management (also called Strategic Management for cultural organizations) systematically seeks for models that allow such equipment to adapt to the constant change that occurs in contemporary societies. In the last decade, the world, and in particular Europe has experienced a serious financial problem that has triggered defensive mechanisms, both in the direction of promoting the balance of public accounts and in the sense of the anonymous loss of the democratic and cultural values of each nation. If in the first case emerged the Troika that led to strong cuts in funding for Culture, deeply affecting those organizations; in the second case, the commonplace citizen is seen fighting for the non-closure of cultural equipment. Despite this, the cultural manager argues that there is no single formula capable of solving the need to adapt to change. In another way, it is up to this agent to know the existing scientific models and to adapt them in the best way to the reality of the institution he coordinates. These actions, as a rule, are concerned with the best performance vis-à-vis external audiences or with the financial sustainability of cultural organizations. They forget, therefore, that all this mechanics cannot function without its internal public, without its Human Resources. The employees of the cultural organization must then have an entrepreneurial posture - must be intrapreneurial. This paper intends to break this form of action and lead the cultural manager to understand that his role should be in the sense of creating value for society, through a good organizational performance. This is only possible with a posture of strategic entrepreneurship. In other words, with a link between: Cultural Management, Cultural Entrepreneurship and Cultural Intrapreneurship. In order to prove this assumption, the case study methodology was used with the symbol of the European Capital of Culture (Casa da Música) as well as qualitative and quantitative techniques. The qualitative techniques included the procedure of in-depth interviews to managers, founders and patrons and focus groups to public with and without experience in managing cultural facilities. The quantitative techniques involved the application of a questionnaire to middle management and employees of Casa da Música. After the triangulation of the data, it was proved that contemporary management of cultural organizations must implement among its practices, the concept of Strategic Entrepreneurship and its variables. Also, the topics which characterize the Cultural Intrapreneurship notion (job satisfaction, the quality in organizational performance, the leadership and the employee engagement and autonomy) emerged. The findings show then that to be sustainable, a cultural organization should meet the concerns of both external and internal forum. In other words, it should have an attitude of citizenship to the communities, visible on a social responsibility and a participatory management, only possible with the implementation of the concept of Strategic Entrepreneurship and its variable of Cultural Intrapreneurship.Keywords: cultural entrepreneurship, cultural intrapreneurship, cultural organizations, strategic management
Procedia PDF Downloads 182138 Combination Therapies Targeting Apoptosis Pathways in Pediatric Acute Myeloid Leukemia (AML)
Authors: Ahlam Ali, Katrina Lappin, Jaine Blayney, Ken Mills
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Leukaemia is the most frequently (30%) occurring type of paediatric cancer. Of these, approximately 80% are acute lymphoblastic leukaemia (ALL) with acute myeloid leukaemia (AML) cases making up the remaining 20% alongside other leukaemias. Unfortunately, children with AML do not have promising prognosis with only 60% surviving 5 years or longer. It has been highlighted recently the need for age-specific therapies for AML patients, with paediatric AML cases having a different mutational landscape compared with AML diagnosed in adult patients. Drug Repurposing is a recognized strategy in drug discovery and development where an already approved drug is used for diseases other than originally indicated. We aim to identify novel combination therapies with the promise of providing alternative more effective and less toxic induction therapy options. Our in-silico analysis highlighted ‘cell death and survival’ as an aberrant, potentially targetable pathway in paediatric AML patients. On this basis, 83 apoptotic inducing compounds were screened. A preliminary single agent screen was also performed to eliminate potentially toxic chemicals, then drugs were constructed into a pooled library with 10 drugs per well over 160 wells, with 45 possible pairs and 120 triples in each well. Seven cell lines were used during this study to represent the clonality of AML in paediatric patients (Kasumi-1, CMK, CMS, MV11-14, PL21, THP1, MOLM-13). Cytotoxicity was assessed up to 72 hours using CellTox™ Green reagent. Fluorescence readings were normalized to a DMSO control. Z-Score was assigned to each well based on the mean and standard deviation of all the data. Combinations with a Z-Score <2 were eliminated and the remaining wells were taken forward for further analysis. A well was considered ‘successful’ if each drug individually demonstrated a Z-Score <2, while the combination exhibited a Z-Score >2. Each of the ten compounds in one well (155) had minimal or no effect as single agents on cell viability however, a combination of two or more of the compounds resulted in a substantial increase in cell death, therefore the ten compounds were de-convoluted to identify a possible synergistic pair/triple combinations. The screen identified two possible ‘novel’ drug pairing, with BCL2 inhibitor ABT-737, combined with either a CDK inhibitor Purvalanol A, or AKT/ PI3K inhibitor LY294002. (ABT-737- 100 nM+ Purvalanol A- 1 µM) (ABT-737- 100 nM+ LY294002- 2 µM). Three possible triple combinations were identified (LY2409881+Akti-1/2+Purvalanol A, SU9516+Akti-1/2+Purvalanol A, and ABT-737+LY2409881+Purvalanol A), which will be taken forward for examining their efficacy at varying concentrations and dosing schedules, across multiple paediatric AML cell lines for optimisation of maximum synergy. We believe that our combination screening approach has potential for future use with a larger cohort of drugs including FDA approved compounds and patient material.Keywords: AML, drug repurposing, ABT-737, apoptosis
Procedia PDF Downloads 202