Search results for: nuclear identity
Commenced in January 2007
Frequency: Monthly
Edition: International
Paper Count: 2460

Search results for: nuclear identity

30 An Explorative Analysis of Effective Project Management of Research and Research-Related Projects within a recently Formed Multi-Campus Technology University

Authors: Àidan Higgins

Abstract:

Higher education will be crucial in the coming decades in helping to make Ireland a nation is known for innovation, competitive enterprise, and ongoing academic success, as well as a desirable location to live and work with a high quality of life, vibrant culture, and inclusive social structures. Higher education institutions will actively connect with each student community, society, and business; they will help students develop a sense of place and identity in Ireland and provide the tools they need to contribute significantly to the global community. It will also serve as a catalyst for novel ideas through research, many of which will become the foundation for long-lasting inventive businesses in the future as part of the 2030 National Strategy on Education focuses on change and developing our education system with a focus on how we carry out Research. The emphasis is central to knowledge transfer and a consistent research framework with exploiting opportunities and having the necessary expertise. The newly formed Technological Universities (TU) in Ireland are based on a government initiative to create a new type of higher education institution that focuses on applied and industry-focused research and education. The basis of the TU is to bring together two or more existing institutes of technology to create a larger and more comprehensive institution that offers a wider range of programs and services to students and industry partners. The TU model aims to promote collaboration between academia, industry, and community organizations to foster innovation, research, and economic development. The TU model also aims to enhance the student experience by providing a more seamless pathway from undergraduate to postgraduate studies, as well as greater opportunities for work placements and engagement with industry partners. Additionally, the TUs are designed to provide a greater emphasis on applied research, technology transfer, and entrepreneurship, with the goal of fostering innovation and contributing to economic growth. A project is a collection of organised tasks carried out precisely to produce a singular output (product or service) within a given time frame. Project management is a set of activities that facilitates the successful implementation of a project. The significant differences between research and development projects are the (lack of) precise requirements and (the inability to) plan an outcome from the beginning of the project. The evaluation criteria for a research project must consider these and other "particularities" in works; for instance, proving something cannot be done may be a successful outcome. This study intends to explore how a newly established multi-campus technological university manages research projects effectively. The study will identify the potential and difficulties of managing research projects, the tools, resources and processes available in a multi-campus Technological University context and the methods and approaches employed to deal with these difficulties. Key stakeholders like project managers, academics, and administrators will be surveyed as part of the study, which will also involve an explorative investigation of current literature and data. The findings of this study will contribute significantly to creating best practices for project management in this setting and offer insightful information about the efficient management of research projects within a multi-campus technological university.

Keywords: project management, research and research-related projects, multi-campus technology university, processes

Procedia PDF Downloads 41
29 A Modular Solution for Large-Scale Critical Industrial Scheduling Problems with Coupling of Other Optimization Problems

Authors: Ajit Rai, Hamza Deroui, Blandine Vacher, Khwansiri Ninpan, Arthur Aumont, Francesco Vitillo, Robert Plana

Abstract:

Large-scale critical industrial scheduling problems are based on Resource-Constrained Project Scheduling Problems (RCPSP), that necessitate integration with other optimization problems (e.g., vehicle routing, supply chain, or unique industrial ones), thus requiring practical solutions (i.e., modular, computationally efficient with feasible solutions). To the best of our knowledge, the current industrial state of the art is not addressing this holistic problem. We propose an original modular solution that answers the issues exhibited by the delivery of complex projects. With three interlinked entities (project, task, resources) having their constraints, it uses a greedy heuristic with a dynamic cost function for each task with a situational assessment at each time step. It handles large-scale data and can be easily integrated with other optimization problems, already existing industrial tools and unique constraints as required by the use case. The solution has been tested and validated by domain experts on three use cases: outage management in Nuclear Power Plants (NPPs), planning of future NPP maintenance operation, and application in the defense industry on supply chain and factory relocation. In the first use case, the solution, in addition to the resources’ availability and tasks’ logical relationships, also integrates several project-specific constraints for outage management, like, handling of resource incompatibility, updating of tasks priorities, pausing tasks in a specific circumstance, and adjusting dynamic unit of resources. With more than 20,000 tasks and multiple constraints, the solution provides a feasible schedule within 10-15 minutes on a standard computer device. This time-effective simulation corresponds with the nature of the problem and requirements of several scenarios (30-40 simulations) before finalizing the schedules. The second use case is a factory relocation project where production lines must be moved to a new site while ensuring the continuity of their production. This generates the challenge of merging job shop scheduling and the RCPSP with location constraints. Our solution allows the automation of the production tasks while considering the rate expectation. The simulation algorithm manages the use and movement of resources and products to respect a given relocation scenario. The last use case establishes a future maintenance operation in an NPP. The project contains complex and hard constraints, like on Finish-Start precedence relationship (i.e., successor tasks have to start immediately after predecessors while respecting all constraints), shareable coactivity for managing workspaces, and requirements of a specific state of "cyclic" resources (they can have multiple states possible with only one at a time) to perform tasks (can require unique combinations of several cyclic resources). Our solution satisfies the requirement of minimization of the state changes of cyclic resources coupled with the makespan minimization. It offers a solution of 80 cyclic resources with 50 incompatibilities between levels in less than a minute. Conclusively, we propose a fast and feasible modular approach to various industrial scheduling problems that were validated by domain experts and compatible with existing industrial tools. This approach can be further enhanced by the use of machine learning techniques on historically repeated tasks to gain further insights for delay risk mitigation measures.

Keywords: deterministic scheduling, optimization coupling, modular scheduling, RCPSP

Procedia PDF Downloads 161
28 Screening and Improved Production of an Extracellular β-Fructofuranosidase from Bacillus Sp

Authors: Lynette Lincoln, Sunil S. More

Abstract:

With the rising demand of sugar used today, it is proposed that world sugar is expected to escalate up to 203 million tonnes by 2021. Hydrolysis of sucrose (table sugar) into glucose and fructose equimolar mixture is catalyzed by β-D-fructofuranoside fructohydrolase (EC 3.2.1.26), commonly called as invertase. For fluid filled center in chocolates, preparation of artificial honey, as a sweetener and especially to ensure that food stuffs remain fresh, moist and soft for longer spans invertase is applied widely and is extensively being used. From an industrial perspective, properties such as increased solubility, osmotic pressure and prevention of crystallization of sugar in food products are highly desired. Screening for invertase does not involve plate assay/qualitative test to determine the enzyme production. In this study, we use a three-step screening strategy for identification of a novel bacterial isolate from soil which is positive for invertase production. The primary step was serial dilution of soil collected from sugarcane fields (black soil, Maddur region of Mandya district, Karnataka, India) was grown on a Czapek-Dox medium (pH 5.0) containing sucrose as the sole C-source. Only colonies with the capability to utilize/breakdown sucrose exhibited growth. Bacterial isolates released invertase in order to take up sucrose, splitting the disaccharide into simple sugars. Secondly, invertase activity was determined from cell free extract by measuring the glucose released in the medium at 540 nm. Morphological observation of the most potent bacteria was examined by several identification tests using Bergey’s manual, which enabled us to know the genus of the isolate to be Bacillus. Furthermore, this potent bacterial colony was subjected to 16S rDNA PCR amplification and a single discrete PCR amplicon band of 1500 bp was observed. The 16S rDNA sequence was used to carry out BLAST alignment search tool of NCBI Genbank database to obtain maximum identity score of sequence. Molecular sequencing and identification was performed by Xcelris Labs Ltd. (Ahmedabad, India). The colony was identified as Bacillus sp. BAB-3434, indicating to be the first novel strain for extracellular invertase production. Molasses, a by-product of the sugarcane industry is a dark viscous liquid obtained upon crystallization of sugar. An enhanced invertase production and optimization studies were carried out by one-factor-at-a-time approach. Crucial parameters such as time course (24 h), pH (6.0), temperature (45 °C), inoculum size (2% v/v), N-source (yeast extract, 0.2% w/v) and C-source (molasses, 4% v/v) were found to be optimum demonstrating an increased yield. The findings of this study reveal a simple screening method of an extracellular invertase from a rapidly growing Bacillus sp., and selection of best factors that elevate enzyme activity especially utilization of molasses which served as an ideal substrate and also as C-source, results in a cost-effective production under submerged conditions. The invert mixture could be a replacement for table sugar which is an economic advantage and reduce the tedious work of sugar growers. On-going studies involve purification of extracellular invertase and determination of transfructosylating activity as at high concentration of sucrose, invertase produces fructooligosaccharides (FOS) which possesses probiotic properties.

Keywords: Bacillus sp., invertase, molasses, screening, submerged fermentation

Procedia PDF Downloads 208
27 The Securitization of the European Migrant Crisis (2015-2016): Applying the Insights of the Copenhagen School of Security Studies to a Comparative Analysis of Refugee Policies in Bulgaria and Hungary

Authors: Tatiana Rizova

Abstract:

The migrant crisis, which peaked in 2015-2016, posed an unprecedented challenge to the European Union’s (EU) newest member states, including Bulgaria and Hungary. Their governments had to formulate sound migration policies with expediency and sensitivity to the needs of millions of people fleeing violent conflicts in the Middle East and failed states in North Africa. Political leaders in post-communist countries had to carefully coordinate with other EU member states on joint policies and solutions while minimizing the risk of alienating their increasingly anti-migrant domestic constituents. Post-communist member states’ governments chose distinct policy responses to the crisis, which were dictated by factors such as their governments’ partisan stances on migration, their views of the European Union, and the decision to frame the crisis as a security or a humanitarian issue. This paper explores how two Bulgarian governments (Boyko Borisov’s second and third government formed during the 43rd and 44th Bulgarian National Assembly, respectively) navigated the processes of EU migration policy making and managing the expectations of their electorates. Based on a comparative analysis of refugee policies in Bulgaria and Hungary during the height of the crisis (2015-2016) and a temporal analysis of refugee policies in Bulgaria (2015-2018), the paper advances the following conclusions. Drawing on insights of the Copenhagen school of security studies, the paper argues that cultural concerns dominated domestic debates in both Bulgaria and Hungary; both governments framed the issue predominantly as a matter of security rather than humanitarian disaster. Regardless of the similarities in issue framing, however, the two governments sought different paths of tackling the crisis. While the Bulgarian government demonstrated its willingness to comply with EU decisions (such as the proposal for mandatory quotas for refugee relocation), the Hungarian government defied EU directives and became a leading voice of dissent inside the EU. The current Bulgarian government (April 2017 - present) appears to be committed to complying with EU decisions and accepts the strategy of EU burden-sharing, while the Hungarian government has continually snubbed the EU’s appeals for cooperation despite the risk of hefty financial penalties. Hungary’s refugee policies have been influenced by the parliamentary representation of the far right-wing party Movement for a Better Hungary (Jobbik), which has encouraged the majority party (FIDESZ) to adopt harsher anti-migrant rhetoric and more hostile policies toward refugees. Bulgaria’s current government is a coalition of the center-right Citizens for a European Development of Bulgaria (GERB) and its far right-wing junior partners – the United Patriots (comprised of three nationalist political parties). The parliamentary presence of Jobbik in Hungary’s parliament has magnified the anti-migrant stance, rhetoric, and policies of Mr. Orbán’s Civic Alliance; we have yet to observe a substantial increase in the anti-migrant rhetoric and policies in Bulgaria’s case. Analyzing responses to the migrant/refugee crisis is a critical opportunity to understand how issues of cultural identity and belonging, inclusion and exclusion, regional integration and disintegration are debated and molded into policy in Europe’s youngest member states in the broader EU context.

Keywords: Copenhagen School, migrant crisis, refugees, security

Procedia PDF Downloads 101
26 An E-Maintenance IoT Sensor Node Designed for Fleets of Diverse Heavy-Duty Vehicles

Authors: George Charkoftakis, Panagiotis Liosatos, Nicolas-Alexander Tatlas, Dimitrios Goustouridis, Stelios M. Potirakis

Abstract:

E-maintenance is a relatively new concept, generally referring to maintenance management by monitoring assets over the Internet. One of the key links in the chain of an e-maintenance system is data acquisition and transmission. Specifically for the case of a fleet of heavy-duty vehicles, where the main challenge is the diversity of the vehicles and vehicle-embedded self-diagnostic/reporting technologies, the design of the data acquisition and transmission unit is a demanding task. This clear if one takes into account that a heavy-vehicles fleet assortment may range from vehicles with only a limited number of analog sensors monitored by dashboard light indicators and gauges to vehicles with plethora of sensors monitored by a vehicle computer producing digital reporting. The present work proposes an adaptable internet of things (IoT) sensor node that is capable of addressing this challenge. The proposed sensor node architecture is based on the increasingly popular single-board computer – expansion boards approach. In the proposed solution, the expansion boards undertake the tasks of position identification by means of a global navigation satellite system (GNSS), cellular connectivity by means of 3G/long-term evolution (LTE) modem, connectivity to on-board diagnostics (OBD), and connectivity to analog and digital sensors by means of a novel design of expansion board. Specifically, the later provides eight analog plus three digital sensor channels, as well as one on-board temperature / relative humidity sensor. The specific device offers a number of adaptability features based on appropriate zero-ohm resistor placement and appropriate value selection for limited number of passive components. For example, although in the standard configuration four voltage analog channels with constant voltage sources for the power supply of the corresponding sensors are available, up to two of these voltage channels can be converted to provide power to the connected sensors by means of corresponding constant current source circuits, whereas all parameters of analog sensor power supply and matching circuits are fully configurable offering the advantage of covering a wide variety of industrial sensors. Note that a key feature of the proposed sensor node, ensuring the reliable operation of the connected sensors, is the appropriate supply of external power to the connected sensors and their proper matching to the IoT sensor node. In standard mode, the IoT sensor node communicates to the data center through 3G/LTE, transmitting all digital/digitized sensor data, IoT device identity, and position. Moreover, the proposed IoT sensor node offers WiFi connectivity to mobile devices (smartphones, tablets) equipped with an appropriate application for the manual registration of vehicle- and driver-specific information, and these data are also forwarded to the data center. All control and communication tasks of the IoT sensor node are performed by dedicated firmware. It is programmed with a high-level language (Python) on top of a modern operating system (Linux). Acknowledgment: This research has been co-financed by the European Union and Greek national funds through the Operational Program Competitiveness, Entrepreneurship, and Innovation, under the call RESEARCH—CREATE—INNOVATE (project code: T1EDK- 01359, IntelligentLogger).

Keywords: IoT sensor nodes, e-maintenance, single-board computers, sensor expansion boards, on-board diagnostics

Procedia PDF Downloads 128
25 Development of a Mixed-Reality Hands-Free Teleoperated Robotic Arm for Construction Applications

Authors: Damith Tennakoon, Mojgan Jadidi, Seyedreza Razavialavi

Abstract:

With recent advancements of automation in robotics, from self-driving cars to autonomous 4-legged quadrupeds, one industry that has been stagnant is the construction industry. The methodologies used in a modern-day construction site consist of arduous physical labor and the use of heavy machinery, which has not changed over the past few decades. The dangers of a modern-day construction site affect the health and safety of the workers due to performing tasks such as lifting and moving heavy objects and having to maintain unhealthy posture to complete repetitive tasks such as painting, installing drywall, and laying bricks. Further, training for heavy machinery is costly and requires a lot of time due to their complex control inputs. The main focus of this research is using immersive wearable technology and robotic arms to perform the complex and intricate skills of modern-day construction workers while alleviating the physical labor requirements to perform their day-to-day tasks. The methodology consists of mounting a stereo vision camera, the ZED Mini by Stereolabs, onto the end effector of an industrial grade robotic arm, streaming the video feed into the Virtual Reality (VR) Meta Quest 2 (Quest 2) head-mounted display (HMD). Due to the nature of stereo vision, and the similar field-of-views between the stereo camera and the Quest 2, human-vision can be replicated on the HMD. The main advantage this type of camera provides over a traditional monocular camera is it gives the user wearing the HMD a sense of the depth of the camera scene, specifically, a first-person view of the robotic arm’s end effector. Utilizing the built-in cameras of the Quest 2 HMD, open-source hand-tracking libraries from OpenXR can be implemented to track the user’s hands in real-time. A mixed-reality (XR) Unity application can be developed to localize the operator's physical hand motions with the end-effector of the robotic arm. Implementing gesture controls will enable the user to move the robotic arm and control its end-effector by moving the operator’s arm and providing gesture inputs from a distant location. Given that the end effector of the robotic arm is a gripper tool, gripping and opening the operator’s hand will translate to the gripper of the robot arm grabbing or releasing an object. This human-robot interaction approach provides many benefits within the construction industry. First, the operator’s safety will be increased substantially as they can be away from the site-location while still being able perform complex tasks such as moving heavy objects from place to place or performing repetitive tasks such as painting walls and laying bricks. The immersive interface enables precision robotic arm control and requires minimal training and knowledge of robotic arm manipulation, which lowers the cost for operator training. This human-robot interface can be extended to many applications, such as handling nuclear accident/waste cleanup, underwater repairs, deep space missions, and manufacturing and fabrication within factories. Further, the robotic arm can be mounted onto existing mobile robots to provide access to hazardous environments, including power plants, burning buildings, and high-altitude repair sites.

Keywords: construction automation, human-robot interaction, hand-tracking, mixed reality

Procedia PDF Downloads 51
24 Synthesis of Carbonyl Iron Particles Modified with Poly (Trimethylsilyloxyethyl Methacrylate) Nano-Grafts

Authors: Martin Cvek, Miroslav Mrlik, Michal Sedlacik, Tomas Plachy

Abstract:

Magnetorheological elastomers (MREs) are multi-phase composite materials containing micron-sized ferromagnetic particles dispersed in an elastomeric matrix. Their properties such as modulus, damping, magneto-striction, and electrical conductivity can be controlled by an external magnetic field and/or pressure. These features of the MREs are used in the development of damping devices, shock attenuators, artificial muscles, sensors or active elements of electric circuits. However, imperfections on the particle/matrix interfaces result in the lower performance of the MREs when compared with theoretical values. Moreover, magnetic particles are susceptible to corrosion agents such as acid rains or sea humidity. Therefore, the modification of particles is an effective tool for the improvement of MRE performance due to enhanced compatibility between particles and matrix as well as improvements of their thermo-oxidation and chemical stability. In this study, the carbonyl iron (CI) particles were controllably modified with poly(trimethylsilyloxyethyl methacrylate) (PHEMATMS) nano-grafts to develop magnetic core–shell structures exhibiting proper wetting with various elastomeric matrices resulting in improved performance within a frame of rheological, magneto-piezoresistance, pressure-piezoresistance, or radio-absorbing properties. The desired molecular weight of PHEMATMS nano-grafts was precisely tailored using surface-initiated atom transfer radical polymerization (ATRP). The CI particles were firstly functionalized using a 3-aminopropyltriethoxysilane agent, followed by esterification reaction with α-bromoisobutyryl bromide. The ATRP was performed in the anisole medium using ethyl α-bromoisobutyrate as a macroinitiator, N, N´, N´´, N´´-pentamethyldiethylenetriamine as a ligand, and copper bromide as an initiator. To explore the effect PHEMATMS molecular weights on final properties, two variants of core-shell structures with different nano-graft lengths were synthesized, while the reaction kinetics were designed through proper reactant feed ratios and polymerization times. The PHEMATMS nano-grafts were characterized by nuclear magnetic resonance and gel permeation chromatography proving information to their monomer conversions, molecular chain lengths, and low polydispersity indexes (1.28 and 1.35) as the results of the executed ATRP. The successful modifications were confirmed via Fourier transform infrared- and energy-dispersive spectroscopies while expected wavenumber outputs and element presences, respectively, of constituted PHEMATMS nano-grafts, were occurring in the spectra. The surface morphology of bare CI and their PHEMATMS-grafted analogues was further studied by scanning electron microscopy, and the thicknesses of grafted polymeric layers were directly observed by transmission electron microscopy. The contact angles as a measure of particle/matrix compatibility were investigated employing the static sessile drop method. The PHEMATMS nano-grafts enhanced compatibility of hydrophilic CI with low-surface-energy hydrophobic polymer matrix in terms of their wettability and dispersibility in an elastomeric matrix. Thus, the presence of possible defects at the particle/matrix interface is reduced, and higher performance of modified MREs is expected.

Keywords: atom transfer radical polymerization, core-shell, particle modification, wettability

Procedia PDF Downloads 179
23 Tangible Losses, Intangible Traumas: Re-envisioning Recovery Following the Lytton Creek Fire 2021 through Place Attachment Lens

Authors: Tugba Altin

Abstract:

In an era marked by pronounced climate change consequences, communities are observed to confront traumatic events that yield both tangible and intangible repercussions. Such events not only cause discernible damage to the landscape but also deeply affect the intangible aspects, including emotional distress and disruptions to cultural landscapes. The Lytton Creek Fire of 2021 serves as a case in point. Beyond the visible destruction, the less overt but profoundly impactful disturbance to place attachment (PA) is scrutinized. PA, representing the emotional and cognitive bonds individuals establish with their environments, is crucial for understanding how such events impact cultural identity and connection to the land. The study underscores the significance of addressing both tangible and intangible traumas for holistic community recovery. As communities renegotiate their affiliations with altered environments, the cultural landscape emerges as instrumental in shaping place-based identities. This renewed understanding is pivotal for reshaping adaptation planning. The research advocates for adaptation strategies rooted in the lived experiences and testimonies of the affected populations. By incorporating both the tangible and intangible facets of trauma, planning efforts are suggested to be more culturally attuned and emotionally insightful, fostering true resonance with the affected communities. Through such a comprehensive lens, this study contributes enriching the climate change discourse, emphasizing the intertwined nature of tangible recovery and the imperative of emotional and cultural healing after environmental disasters. Following the pronounced aftermath of the Lytton Creek Fire in 2021, research aims to deeply understand its impact on place attachment (PA), encompassing the emotional and cognitive bonds individuals form with their environments. The interpretive phenomenological approach, enriched by a hermeneutic framework, is adopted, emphasizing the experiences of the Lytton community and co-researchers. Phenomenology informed the understanding of 'place' as the focal point of attachment, providing insights into its formation and evolution after traumatic events. Data collection departs from conventional methods. Instead of traditional interviews, walking audio sessions and photo elicitation methods are utilized. These allow co-researchers to immerse themselves in the environment, re-experience, and articulate memories and feelings in real-time. Walking audio facilitates reflections on spatial narratives post-trauma, while photo voices captured intangible emotions, enabling the visualization of place-based experiences. The analysis is collaborative, ensuring the co-researchers' experiences and interpretations are central. Emphasizing their agency in knowledge production, the process is rigorous, facilitated by the harmonious blend of interpretive phenomenology and hermeneutic insights. The findings underscore the need for adaptation and recovery efforts to address emotional traumas alongside tangible damages. By exploring PA post-disaster, the research not only fills a significant gap but advocates for an inclusive approach to community recovery. Furthermore, the participatory methodologies employed challenge traditional research paradigms, heralding potential shifts in qualitative research norms.

Keywords: wildfire recovery, place attachment, trauma recovery, cultural landscape, visual methodologies

Procedia PDF Downloads 52
22 Wellbeing Effects from Family Literacy Education: An Ecological Study

Authors: Jane Furness, Neville Robertson, Judy Hunter, Darrin Hodgetts, Linda Nikora

Abstract:

Background and significance: This paper describes the first use of community psychology theories to investigate family-focused literacy education programmes, enabling a wide range of wellbeing effects of such programmes to be identified for the first time. Evaluations of family literacy programmes usually focus on the economic advantage of gains in literacy skills. By identifying other effects on aspects of participants’ lives that are important to them, and how they occur, understanding of how such programmes contribute to wellbeing and social justice is augmented. Drawn from community psychology, an ecological systems-based, culturally adaptive framework for personal, relational and collective wellbeing illuminated outcomes of family literacy programmes that enhanced wellbeing and quality of life for adult participants, their families and their communities. All programmes, irrespective of their institutional location, could be similarly scrutinized. Methodology: The study traced the experiences of nineteen adult participants in four family-focused literacy programmes located in geographically and culturally different communities throughout New Zealand. A critical social constructionist paradigm framed this interpretive study. Participants were mainly Māori, Pacific islands, or European New Zealanders. Seventy-nine repeated conversational interviews were conducted over 18 months with the adult participants, programme staff and people who knew the participants well. Twelve participant observations of programme sessions were conducted, and programme documentation was reviewed. Latent theoretical thematic analysis of data drew on broad perspectives of literacy and ecological systems theory, network theory and holistic, integrative theories of wellbeing. Steps taken to co-construct meaning with participants included the repeated conversational interviews and participant checking of interview transcripts and section drafts. The researcher (this paper’s first author) followed methodological guidelines developed by indigenous peoples for non-indigenous researchers. Findings: The study found that the four family literacy programmes, differing in structure, content, aims and foci, nevertheless shared common principles and practices that reflected programme staff’s overarching concern for people’s wellbeing along with their desire to enhance literacy abilities. A human rights and strengths-based based view of people based on respect for diverse culturally based values and practices were evident in staff expression of their values and beliefs and in their practices. This enacted stance influenced the outcomes of programme participation for the adult participants, their families and their communities. Alongside the literacy and learning gains identified, participants experienced positive social and relational events and changes, affirmation and strengthening of their culturally based values, and affirmation and building of positive identity. Systemically, interconnectedness of programme effects with participants’ personal histories and circumstances; the flow on of effects to other aspects of people’s lives and to their families and communities; and the personalised character of the pathways people journeyed towards enhanced wellbeing were identified. Concluding statement: This paper demonstrates the critical contribution of community psychology to a fuller understanding of family-focused educational programme outcomes than has been previously attainable, the meaning of these broader outcomes to people in their lives, and their role in wellbeing and social justice.

Keywords: community psychology, ecological theory, family literacy education, flow on effects, holistic wellbeing

Procedia PDF Downloads 226
21 Internet of Assets: A Blockchain-Inspired Academic Program

Authors: Benjamin Arazi

Abstract:

Blockchain is the technology behind cryptocurrencies like Bitcoin. It revolutionizes the meaning of trust in the sense of offering total reliability without relying on any central entity that controls or supervises the system. The Wall Street Journal states: “Blockchain Marks the Next Step in the Internet’s Evolution”. Blockchain was listed as #1 in Linkedin – The Learning Blog “most in-demand hard skills needed in 2020”. As stated there: “Blockchain’s novel way to store, validate, authorize, and move data across the internet has evolved to securely store and send any digital asset”. GSMA, a leading Telco organization of mobile communications operators, declared that “Blockchain has the potential to be for value what the Internet has been for information”. Motivated by these seminal observations, this paper presents the foundations of a Blockchain-based “Internet of Assets” academic program that joins under one roof leading application areas that are characterized by the transfer of assets over communication lines. Two such areas, which are pillars of our economy, are Fintech – Financial Technology and mobile communications services. The next application in line is Healthcare. These challenges are met based on available extensive professional literature. Blockchain-based assets communication is based on extending the principle of Bitcoin, starting with the basic question: If digital money that travels across the universe can ‘prove its own validity’, can this principle be applied to digital content. A groundbreaking positive answer here led to the concept of “smart contract” and consequently to DLT - Distributed Ledger Technology, where the word ‘distributed’ relates to the non-existence of reliable central entities or trusted third parties. The terms Blockchain and DLT are frequently used interchangeably in various application areas. The World Bank Group compiled comprehensive reports, analyzing the contribution of DLT/Blockchain to Fintech. The European Central Bank and Bank of Japan are engaged in Project Stella, “Balancing confidentiality and auditability in a distributed ledger environment”. 130 DLT/Blockchain focused Fintech startups are now operating in Switzerland. Blockchain impact on mobile communications services is treated in detail by leading organizations. The TM Forum is a global industry association in the telecom industry, with over 850 member companies, mainly mobile operators, that generate US$2 trillion in revenue and serve five billion customers across 180 countries. From their perspective: “Blockchain is considered one of the digital economy’s most disruptive technologies”. Samples of Blockchain contributions to Fintech (taken from a World Bank document): Decentralization and disintermediation; Greater transparency and easier auditability; Automation & programmability; Immutability & verifiability; Gains in speed and efficiency; Cost reductions; Enhanced cyber security resilience. Samples of Blockchain contributions to the Telco industry. Establishing identity verification; Record of transactions for easy cost settlement; Automatic triggering of roaming contract which enables near-instantaneous charging and reduction in roaming fraud; Decentralized roaming agreements; Settling accounts per costs incurred in accordance with agreement tariffs. This clearly demonstrates an academic education structure where fundamental technologies are studied in classes together with these two application areas. Advanced courses, treating specific implementations then follow separately. All are under the roof of “Internet of Assets”.

Keywords: blockchain, education, financial technology, mobile telecommunications services

Procedia PDF Downloads 155
20 Nonlinear Homogenized Continuum Approach for Determining Peak Horizontal Floor Acceleration of Old Masonry Buildings

Authors: Andreas Rudisch, Ralf Lampert, Andreas Kolbitsch

Abstract:

It is a well-known fact among the engineering community that earthquakes with comparatively low magnitudes can cause serious damage to nonstructural components (NSCs) of buildings, even when the supporting structure performs relatively well. Past research works focused mainly on NSCs of nuclear power plants and industrial plants. Particular attention should also be given to architectural façade elements of old masonry buildings (e.g. ornamental figures, balustrades, vases), which are very vulnerable under seismic excitation. Large numbers of these historical nonstructural components (HiNSCs) can be found in highly frequented historical city centers and in the event of failure, they pose a significant danger to persons. In order to estimate the vulnerability of acceleration sensitive HiNSCs, the peak horizontal floor acceleration (PHFA) is used. The PHFA depends on the dynamic characteristics of the building, the ground excitation, and induced nonlinearities. Consequently, the PHFA can not be generalized as a simple function of height. In the present research work, an extensive case study was conducted to investigate the influence of induced nonlinearity on the PHFA for old masonry buildings. Probabilistic nonlinear FE time-history analyses considering three different hazard levels were performed. A set of eighteen synthetically generated ground motions was used as input to the structure models. An elastoplastic macro-model (multiPlas) for nonlinear homogenized continuum FE-calculation was calibrated to multiple scales and applied, taking specific failure mechanisms of masonry into account. The macro-model was calibrated according to the results of specific laboratory and cyclic in situ shear tests. The nonlinear macro-model is based on the concept of multi-surface rate-independent plasticity. Material damage or crack formation are detected by reducing the initial strength after failure due to shear or tensile stress. As a result, shear forces can only be transmitted to a limited extent by friction when the cracking begins. The tensile strength is reduced to zero. The first goal of the calibration was the consistency of the load-displacement curves between experiment and simulation. The calibrated macro-model matches well with regard to the initial stiffness and the maximum horizontal load. Another goal was the correct reproduction of the observed crack image and the plastic strain activities. Again the macro-model proved to work well in this case and shows very good correlation. The results of the case study show that there is significant scatter in the absolute distribution of the PHFA between the applied ground excitations. An absolute distribution along the normalized building height was determined in the framework of probability theory. It can be observed that the extent of nonlinear behavior varies for the three hazard levels. Due to the detailed scope of the present research work, a robust comparison with code-recommendations and simplified PHFA distributions are possible. The chosen methodology offers a chance to determine the distribution of PHFA along the building height of old masonry structures. This permits a proper hazard assessment of HiNSCs under seismic loads.

Keywords: nonlinear macro-model, nonstructural components, time-history analysis, unreinforced masonry

Procedia PDF Downloads 144
19 Kanga Traditional Costume as a Tool for Community Empowerment in Tanzania in Ubuntu perspective - A Literature Review

Authors: Meinrad Haule Lembuka

Abstract:

Introduction: Ubuntu culture represents African humanism with collective and positive feeling of people living together, interdependence, equally and peaceful etc. Overtime, Ubuntu culture developed varieties of communicative strategies to express experiences, feelings and knowledge. Khanga or kanga (garment) is among the Ubuntu cultural practice of Bantu speaking people along the East African coast following interaction with Arabs and Bantu speaking people to formulate Swahili culture. Kanga or Kanga is a Swahili word which means a traditional soft cotton cloths in varieties of colours, patterns, and styles which as a deep cultural, historical, and social significance not only in Tanzania but the rest of East African coast. Swahili culture is a sub culture of Ubuntu African culture which is rich in customs and rituals that serve to preserve goodness and life where Tanzania, like the rest of East African societies along the Indian coast engaged in kanga dressing custom under Swahili culture to express their feelings and knowledge sharing. After the independence of Tanzania (formerly Tanganyika) from British colonial rule, Kanga traditional dressing gained momentum in Swahili culture and spread to the rest of East Africa and beyond. To date kanga dressing holds a good position as a formal and informal tool for advocating marginalised groups, counselling, psychosocial therapy, liberation, compassion, love, justice, campaign, and cerebration etc. Methodology: A literature review method was guided by Ubuntu theory to assess the implications of kanga traditional dressing in empowering Tanzanian community. Findings: During slavery, slaves wore Kaniki and people despised Kaniki dressing due to its association with slavery. Ex-slave women seeking to become part of the Swahili society began to decorate their Kaniki clothes. After slavery was abolished in 1897, Kangas began to be used for self-empowerment and to indicate that the wearer had personal wealth. During colonial era, freedom of expressions for Africans were restricted by colonial masters thus Tanzanians used kanga to express the evils of colonialism and other social problems, Under Ubuntu value of unity and solidarity liberation and independence fighters crafted motto and liberation messages that were shared and spread rapidly in the community. Political parities like TANU used kanga to spread nationalism and Ujamaa policy. kanga is more than a piece of fabric-it is a space for women to voice unspeakable communication and a women-centred repository for indigenous knowledge, feminisms addressing social ills, happiness, campaigns, memories and reconciliation etc. Kanga provides an indirect voice and support vulnerable and marginalised populations and strongly it has proved to be a peaceful platform of capture attention of government and societies. Kanga textiles gained increased international fame when an Obama kanga design was produced upon the president’s election in 2008 and his visit to Tanzania in 2013. Conclusion: Kanga preserves and symbolises Swahili culture and contributes in realization of social justice, inclusion, national identity and unity. As an inclusive cultural tool, Kanga spread across Africa to international community and the practice has moved from being a woman domination dressing code to other sex orientations.

Keywords: African culture, Kanga, khanga, swahili culture, ubuntu

Procedia PDF Downloads 41
18 MusicTherapy for Actors: An Exploratory Study Applied to Students from University Theatre Faculty

Authors: Adriana De Serio, Adrian Korek

Abstract:

Aims: This experiential research work presents a Group-MusicTherapy-Theatre-Plan (MusThePlan) the authors have carried out to support the actors. The MusicTherapy gives rise to individual psychophysical feedback and influences the emotional centres of the brain and the subconsciousness. Therefore, the authors underline the effectiveness of the preventive, educational, and training goals of the MusThePlan to lead theatre students and actors to deal with anxiety and to overcome psychophysical weaknesses, shyness, emotional stress in stage performances, to increase flexibility, awareness of one's identity and resources for a positive self-development and psychophysical health, to develop and strengthen social bonds, increasing a network of subjects working for social inclusion and reduction of stigma. Materials-Methods: Thirty students from the University Theatre Faculty participated in weekly music therapy sessions for two months; each session lasted 120 minutes. MusThePlan: Each session began with a free group rhythmic-sonorous-musical-production by body-percussion, voice-canto, instruments, to stimulate communication. Then, a synchronized-structured bodily-rhythmic-sonorous-musical production also involved acting, dances, movements of hands and arms, hearing, and more sensorial perceptions and speech to balance motor skills and the muscular tone. Each student could be the director-leader of the group indicating a story to inspire the group's musical production. The third step involved the students in rhythmic speech and singing drills and in vocal exercises focusing on the musical pitch to improve the intonation and on the diction to improve the articulation and lead up it to an increased intelligibility. At the end of each musictherapy session and of the two months, the Musictherapy Assessment Document was drawn up by analysis of observation protocols and two Indices by the authors: Patient-Environment-Music-Index (time to - tn) to estimate the behavior evolution, Somatic Pattern Index to monitor subject’s eye and mouth and limb motility, perspiration, before, during and after musictherapy sessions. Results: After the first month, the students (non musicians) learned to play percussion instruments and formed a musical band that played classical/modern music on the percussion instruments with the musictherapist/pianist/conductor in a public concert. At the end of the second month, the students performed a public musical theatre show, acting, dancing, singing, and playing percussion instruments. The students highlighted the importance of the playful aspects of the group musical production in order to achieve emotional contact and harmony within the group. The students said they had improved kinetic and vocal and all the skills useful for acting activity and the nourishment of the bodily and emotional balance. Conclusions: The MusThePlan makes use of some specific MusicTherapy methodological models, techniques, and strategies useful for the actors. The MusThePlan can destroy the individual "mask" and can be useful when the verbal language is unable to undermine the defense mechanisms of the subject. The MusThePlan improves actor’s psychophysical activation, motivation, gratification, knowledge of one's own possibilities, and the quality of life. Therefore, the MusThePlan could be useful to carry out targeted interventions for the actors with characteristics of repeatability, objectivity, and predictability of results. Furthermore, it would be useful to plan a University course/master in “MusicTherapy for the Theatre”.

Keywords: musictherapy, sonorous-musical energy, quality of life, theatre

Procedia PDF Downloads 43
17 The Proposal for a Framework to Face Opacity and Discrimination ‘Sins’ Caused by Consumer Creditworthiness Machines in the EU

Authors: Diogo José Morgado Rebelo, Francisco António Carneiro Pacheco de Andrade, Paulo Jorge Freitas de Oliveira Novais

Abstract:

Not everything in AI-power consumer credit scoring turns out to be a wonder. When using AI in Creditworthiness Assessment (CWA), opacity and unfairness ‘sins’ must be considered to the task be deemed Responsible. AI software is not always 100% accurate, which can lead to misclassification. Discrimination of some groups can be exponentiated. A hetero personalized identity can be imposed on the individual(s) affected. Also, autonomous CWA sometimes lacks transparency when using black box models. However, for this intended purpose, human analysts ‘on-the-loop’ might not be the best remedy consumers are looking for in credit. This study seeks to explore the legality of implementing a Multi-Agent System (MAS) framework in consumer CWA to ensure compliance with the regulation outlined in Article 14(4) of the Proposal for an Artificial Intelligence Act (AIA), dated 21 April 2021 (as per the last corrigendum by the European Parliament on 19 April 2024), Especially with the adoption of Art. 18(8)(9) of the EU Directive 2023/2225, of 18 October, which will go into effect on 20 November 2026, there should be more emphasis on the need for hybrid oversight in AI-driven scoring to ensure fairness and transparency. In fact, the range of EU regulations on AI-based consumer credit will soon impact the AI lending industry locally and globally, as shown by the broad territorial scope of AIA’s Art. 2. Consequently, engineering the law of consumer’s CWA is imperative. Generally, the proposed MAS framework consists of several layers arranged in a specific sequence, as follows: firstly, the Data Layer gathers legitimate predictor sets from traditional sources; then, the Decision Support System Layer, whose Neural Network model is trained using k-fold Cross Validation, provides recommendations based on the feeder data; the eXplainability (XAI) multi-structure comprises Three-Step-Agents; and, lastly, the Oversight Layer has a 'Bottom Stop' for analysts to intervene in a timely manner. From the analysis, one can assure a vital component of this software is the XAY layer. It appears as a transparent curtain covering the AI’s decision-making process, enabling comprehension, reflection, and further feasible oversight. Local Interpretable Model-agnostic Explanations (LIME) might act as a pillar by offering counterfactual insights. SHapley Additive exPlanation (SHAP), another agent in the XAI layer, could address potential discrimination issues, identifying the contribution of each feature to the prediction. Alternatively, for thin or no file consumers, the Suggestion Agent can promote financial inclusion. It uses lawful alternative sources such as the share of wallet, among others, to search for more advantageous solutions to incomplete evaluation appraisals based on genetic programming. Overall, this research aspires to bring the concept of Machine-Centered Anthropocentrism to the table of EU policymaking. It acknowledges that, when put into service, credit analysts no longer exert full control over the data-driven entities programmers have given ‘birth’ to. With similar explanatory agents under supervision, AI itself can become self-accountable, prioritizing human concerns and values. AI decisions should not be vilified inherently. The issue lies in how they are integrated into decision-making and whether they align with non-discrimination principles and transparency rules.

Keywords: creditworthiness assessment, hybrid oversight, machine-centered anthropocentrism, EU policymaking

Procedia PDF Downloads 14
16 Implementation of Green Deal Policies and Targets in Energy System Optimization Models: The TEMOA-Europe Case

Authors: Daniele Lerede, Gianvito Colucci, Matteo Nicoli, Laura Savoldi

Abstract:

The European Green Deal is the first internationally agreed set of measures to contrast climate change and environmental degradation. Besides the main target of reducing emissions by at least 55% by 2030, it sets the target of accompanying European countries through an energy transition to make the European Union into a modern, resource-efficient, and competitive net-zero emissions economy by 2050, decoupling growth from the use of resources and ensuring a fair adaptation of all social categories to the transformation process. While the general purpose to allow the realization of the purposes of the Green Deal already dates back to 2019, strategies and policies keep being developed coping with recent circumstances and achievements. However, general long-term measures like the Circular Economy Action Plan, the proposals to shift from fossil natural gas to renewable and low-carbon gases, in particular biomethane and hydrogen, and to end the sale of gasoline and diesel cars by 2035, will all have significant effects on energy supply and demand evolution across the next decades. The interactions between energy supply and demand over long-term time frames are usually assessed via energy system models to derive useful insights for policymaking and to address technological choices and research and development. TEMOA-Europe is a newly developed energy system optimization model instance based on the minimization of the total cost of the system under analysis, adopting a technologically integrated, detailed, and explicit formulation and considering the evolution of the system in partial equilibrium in competitive markets with perfect foresight. TEMOA-Europe is developed on the TEMOA platform, an open-source modeling framework totally implemented in Python, therefore ensuring third-party verification even on large and complex models. TEMOA-Europe is based on a single-region representation of the European Union and EFTA countries on a time scale between 2005 and 2100, relying on a set of assumptions for socio-economic developments based on projections by the International Energy Outlook and a large technological dataset including 7 sectors: the upstream and power sectors for the production of all energy commodities and the end-use sectors, including industry, transport, residential, commercial and agriculture. TEMOA-Europe also includes an updated hydrogen module considering its production, storage, transportation, and utilization. Besides, it can rely on a wide set of innovative technologies, ranging from nuclear fusion and electricity plants equipped with CCS in the power sector to electrolysis-based steel production processes and steel in the industrial sector – with a techno-economic characterization based on public literature – to produce insightful energy scenarios and especially to cope with the very long analyzed time scale. The aim of this work is to examine in detail the scheme of measures and policies for the realization of the purposes of the Green Deal and to transform them into a set of constraints and new socio-economic development pathways. Based on them, TEMOA-Europe will be used to produce and comparatively analyze scenarios to assess the consequences of Green Deal-related measures on the future evolution of the energy mix over the whole energy system in an economic optimization environment.

Keywords: European Green Deal, energy system optimization modeling, scenario analysis, TEMOA-Europe

Procedia PDF Downloads 83
15 Significant Aspects and Drivers of Germany and Australia's Energy Policy from a Political Economy Perspective

Authors: Sarah Niklas, Lynne Chester, Mark Diesendorf

Abstract:

Geopolitical tensions, climate change and recent movements favouring a transformative shift in institutional power structures have influenced the economics of conventional energy supply for decades. This study takes a multi-dimensional approach to illustrate the potential of renewable energy (RE) technology to provide a pathway to a low-carbon economy driven by ecologically sustainable, independent and socially just energy. This comparative analysis identifies economic, political and social drivers that shaped the adoption of RE policy in two significantly different economies, Germany and Australia, with strong and weak commitments to RE respectively. Two complementary political-economy theories frame the document-based analysis. Régulation Theory, inspired by Marxist ideas and strongly influenced by contemporary economic problems, provides the background to explore the social relationships contributing the adoption of RE within the macro-economy. Varieties of Capitalism theory, a more recently developed micro-economic approach, examines the nature of state-firm relationships. Together these approaches provide a comprehensive lens of analysis. Germany’s energy policy transformed substantially over the second half of the last century. The development is characterised by the coordination of societal, environmental and industrial demands throughout the advancement of capitalist regimes. In the Fordist regime, mass production based on coal drove Germany’s astounding economic recovery during the post-war period. Economic depression and the instability of institutional arrangements necessitated the impulsive seeking of national security and energy independence. During the postwar Flexi-Fordist period, quality-based production, innovation and technology-based competition schemes, particularly with regard to political power structures in and across Europe, favoured the adoption of RE. Innovation, knowledge and education were institutionalized, leading to the legislation of environmental concerns. Lastly the establishment of government-industry-based coordinative programs supported the phase out of nuclear power and the increased adoption of RE during the last decade. Australia’s energy policy is shaped by the country’s richness in mineral resources. Energy policy largely served coal mining, historically and currently one of the most capital-intense industry. Assisted by the macro-economic dimensions of institutional arrangements, social and financial capital is orientated towards the export-led and strongly demand-oriented economy. Here energy policy serves the maintenance of capital accumulation in the mining sector and the emerging Asian economies. The adoption of supportive renewable energy policy would challenge the distinct role of the mining industry within the (neo)-liberal market economy. The state’s protective role of the mining sector has resulted in weak commitment to RE policy and investment uncertainty in the energy sector. Recent developments, driven by strong public support for RE, emphasize the sense of community in urban and rural areas and the emergence of a bottom-up approach to adopt renewables. Thus, political economy frameworks on both the macro-economic (Regulation Theory) and micro-economic (Varieties of Capitalism theory) scales can together explain the strong commitment to RE in Germany vis-à-vis the weak commitment in Australia.

Keywords: political economy, regulation theory, renewable energy, social relationships, energy transitions

Procedia PDF Downloads 360
14 Physico-Chemical Characterization of Vegetable Oils from Oleaginous Seeds (Croton megalocarpus, Ricinus communis L., and Gossypium hirsutum L.)

Authors: Patrizia Firmani, Sara Perucchini, Irene Rapone, Raffella Borrelli, Stefano Chiaberge, Manuela Grande, Rosamaria Marrazzo, Alberto Savoini, Andrea Siviero, Silvia Spera, Fabio Vago, Davide Deriu, Sergio Fanutti, Alessandro Oldani

Abstract:

According to the Renewable Energy Directive II, the use of palm oil in diesel will be gradually reduced from 2023 and should reach zero in 2030 due to the deforestation caused by its production. Eni aims at finding alternative feedstocks for its biorefineries to eliminate the use of palm oil by 2023. Therefore, the ideal vegetable oils to be used in bio-refineries are those obtainable from plants that grow in marginal lands and with low impact on food-and-feed chain; hence, Eni research is studying the possibility of using oleaginous seeds, such as castor, croton, and cotton, to extract the oils to be exploited as feedstock in bio-refineries. To verify their suitability for the upgrading processes, an analytical protocol for their characterization has been drawn up and applied. The analytical characterizations include a step of water and ashes content determination, elemental analysis (CHNS analysis, X-Ray Fluorescence, Inductively Coupled Plasma - Optical Emission Spectroscopy, ICP– Mass Spectrometry), and total acid number determination. Gas chromatography coupled to flame ionization detector (GC-FID) is used to quantify the lipid content in terms of free fatty acids, mono-, di- and triacylglycerols, and fatty acids composition. Eventually, Nuclear Magnetic Resonance and Fourier Transform-Infrared spectroscopies are exploited with GC-MS and Fourier Transform-Ion Cyclotron Resonance to study the composition of the oils. This work focuses on the GC-FID analysis of the lipid fraction of these oils, as the main constituent and of greatest interest for bio-refinery processes. Specifically, the lipid component of the extracted oil was quantified after sample silanization and transmethylation: silanization allows the elution of high-boiling compounds and is useful for determining the quantity of free acids and glycerides in oils, while transmethylation leads to a mixture of fatty acid esters and glycerol, thus allowing to evaluate the composition of glycerides in terms of Fatty Acids Methyl Esters (FAME). Cotton oil was extracted from cotton oilcake, croton oil was obtained by seeds pressing and seeds and oilcake ASE extraction, while castor oil comes from seed pressing (not performed in Eni laboratories). GC-FID analyses reported that the cotton oil is 90% constituted of triglycerides and about 6% diglycerides, while free fatty acids are about 2%. In terms of FAME, C18 acids make up 70% of the total and linoleic acid is the major constituent. Palmitic acid is present at 17.5%, while the other acids are in low concentration (<1%). Both analyzes show the presence of non-gas chromatographable compounds. Croton oils from seed pressing and extraction mainly contain triglycerides (98%). Concerning FAME, the main component is linoleic acid (approx. 80%). Oilcake croton oil shows higher abundance of diglycerides (6% vs ca 2%) and a lower content of triglycerides (38% vs 98%) compared to the previous oils. Eventually, castor oil is mostly constituted of triacylglycerols (about 69%), followed by diglycerides (about 10%). About 85.2% of total FAME is ricinoleic acid, as a constituent of triricinolein, the most abundant triglyceride of castor oil. Based on the analytical results, these oils represent feedstocks of interest for possible exploitation as advanced biofuels.

Keywords: analytical protocol, biofuels, biorefinery, gas chromatography, vegetable oil

Procedia PDF Downloads 113
13 Molecular Signaling Involved in the 'Benzo(a)Pyrene' Induced Germ Cell DNA Damage and Apoptosis: Possible Protection by Natural Aryl Hydrocarbon Receptor Antagonist and Anti-Tumor Agent

Authors: Kuladip Jana

Abstract:

Benzo(a)pyrene [B(a)P] is an environmental toxicant present mostly in cigarette smoke and car exhaust, is an aryl hydrocarbon receptor (AhR) ligand that exerts its toxic effects on both male and female reproductive systems. In this study, the effect of B(a)P at different doses (0.1, 0.25, 0.5, 1 and 5 mg /kg body weight) was studied on male reproductive system of rat. A significant decrease in cauda epididymal sperm count and motility along with the presence of sperm head abnormalities and altered epididymal and testicular histology were documented following B(a)P treatment. B(a)P treatment resulted apoptotic sperm cells as observed by TUNEL and Annexin V-PI assay with increased ROS, altered sperm mitochondrial membrane potential (ΔΨm) with a simultaneous decrease in the activity of antioxidant enzymes and GSH status. TUNEL positive apoptotic cells also observed in testis as well as isolated germ and Leydig cells following B(a)P exposure. Western Blot analysis revealed the activation of p38MAPK, cytosolic translocation of cytochrome-c, up-regulation of Bax and inducible nitric oxide synthase (iNOS) with cleavage of PARP and down-regulation of BCl2 in testis upon B(a)P treatment. The protein and mRNA levels of testicular key steroidogenesis regulatory proteins like StAR, cytochrome P450 IIA1 (CYPIIA1), 3β HSD, 17β HSD showed a significant decrease in a dose dependent manner while an increase in the expression of cytochrome P450 1A1 (CYP1A1), Aryl hydrocarbon Receptor (AhR), active caspase- 9 and caspase- 3 following B(a)P exposure. We conclude that exposure of benzo(a)pyrene caused testicular gamatogenic and steroidogenic disorders by induction of oxidative stress, inhibition of StAR and other steroidogenic enzymes along with activation of p38MAPK and initiated caspase-3 mediated germ and Leydig cell apoptosis.The possible protective role of naturally occurring phytochemicals against B(a)P induced testicular toxicity needs immediate consideration. Curcumin and resveratrol separately were found to protect against B(a)P induced germ cell apoptosis, and their combinatorial effect was more significant. Our present study in isolated testicular germ cell population from adult male Wistar rats, highlighted their synergistic protective effect against B(a)P induced germ cell apoptosis. Curcumin-resveratrol co-treatment decreased the expression of pro-apoptotic proteins like cleaved caspase 3,8,9, cleaved PARP, Apaf1, FasL, tBid. Curcumin-resveratrol co-treatment decreased Bax/Bcl2 ratio, mitochondria to cytosolic translocation of cytochrome c and activated the survival protein Akt. Curcumin-resveratrol decreased the expression of p53 dependent apoptotic genes like Fas, FasL, Bax, Bcl2, Apaf1.Curcumin-resveratrol co-treatment thus prevented B(a)P induced germ cell apoptosis. B(a)P induced testicular ROS generation and oxidative stress were significantly ameliorated with curcumin and resveratrol. Curcumin-resveratrol co-treatment prevented B(a)P induced nuclear translocation of AhR and CYP1A1 production. The combinatorial treatment significantly inhibited B(a)P induced ERK 1/2, p38 MAPK and JNK 1/2 activation. B(a)P treatment increased the expression of p53 and its phosphorylation (p53 ser 15). Curcumin-resveratrol co-treatment significantly decreased p53 level and its phosphorylation (p53 ser 15). The study concludes that curcumin-resveratrol synergistically modulated MAPKs and p53, prevented oxidative stress, regulated the expression of pro and anti-apoptotic proteins as well as the proteins involved in B(a)P metabolism thus protected germ cells from B(a)P induced apoptosis.

Keywords: benzo(a)pyrene, germ cell, apoptosis, oxidative stress, resveratrol, curcumin

Procedia PDF Downloads 233
12 [Keynote Talk]: Bioactive Cyclic Dipeptides of Microbial Origin in Discovery of Cytokine Inhibitors

Authors: Sajeli A. Begum, Ameer Basha, Kirti Hira, Rukaiyya Khan

Abstract:

Cyclic dipeptides are simple diketopiperazine derivatives being investigated by several scientists for their biological effects which include anticancer, antimicrobial, haematological, anticonvulsant, immunomodulatory effect, etc. They are potentially active microbial metabolites having been synthesized too, for developing into drug candidates. Cultures of Pseudomonas species have earlier been reported to produce cyclic dipeptides, helping in quorum sensing signals and bacterial–host colonization phenomena during infections, causing cell anti-proliferation and immunosuppression. Fluorescing Pseudomonas species have been identified to secrete lipid derivatives, peptides, pyrroles, phenazines, indoles, aminoacids, pterines, pseudomonic acids and some antibiotics. In the present work, results of investigation on the cyclic dipeptide metabolites secreted by the culture broth of Pseudomonas species as potent pro-inflammatory cytokine inhibitors are discussed. The bacterial strain was isolated from the rhizospheric soil of groundnut crop and identified as Pseudomonas aeruginosa by 16S rDNA sequence (GenBank Accession No. KT625586). Culture broth of this strain was prepared by inoculating into King’s B broth and incubating at 30 ºC for 7 days. The ethyl acetate extract of culture broth was prepared and lyophilized to get a dry residue (EEPA). Lipopolysaccharide (LPS)-induced ELISA assay proved the inhibition of tumor necrosis factor-alpha (TNF-α) secretion in culture supernatant of RAW 264.7 cells by EEPA (IC50 38.8 μg/mL). The effect of oral administration of EEPA on plasma TNF-α level in rats was tested by ELISA kit. The LPS mediated plasma TNF-α level was reduced to 45% with 125 mg/kg dose of EEPA. Isolation of the chemical constituents of EEPA through column chromatography yielded ten cyclic dipeptides, which were characterized using nuclear magnetic resonance and mass spectroscopic techniques. These cyclic dipeptides are biosynthesized in microorganisms by multifunctional assembly of non-ribosomal peptide synthases and cyclic dipeptide synthase. Cyclo (Gly-L-Pro) was found to be more potentially (IC50 value 4.5 μg/mL) inhibiting TNF-α production followed by cyclo (trans-4-hydroxy-L-Pro-L-Phe) (IC50 value 14.2 μg/mL) and the effect was equal to that of standard immunosuppressant drug, prednisolone. Further, the effect was analyzed by determining mRNA expression of TNF-α in LPS-stimulated RAW 264.7 macrophages using quantitative real-time reverse transcription polymerase chain reaction. EEPA and isolated cyclic dipeptides demonstrated diminution of TNF-α mRNA expression levels in a dose-dependent manner under the tested conditions. Also, they were found to control the expression of other pro-inflammatory cytokines like IL-1β and IL-6, when tested through their mRNA expression levels in LPS-stimulated RAW 264.7 macrophages under LPS-stimulated conditions. In addition, significant inhibition effect was found on Nitric oxide production. Further all the compounds exhibited weak toxicity to LPS-induced RAW 264.7 cells. Thus the outcome of the study disclosed the effectiveness of EEPA and the isolated cyclic dipeptides in down-regulating key cytokines involved in pathophysiology of autoimmune diseases.In another study led by the investigators, microbial cyclic dipeptides were found to exhibit excellent antimicrobial effect against Fusarium moniliforme which is an important causative agent of Sorghum grain mold disease. Thus, cyclic dipeptides are emerging small molecular drug candidates for various autoimmune diseases.

Keywords: cyclic dipeptides, cytokines, Fusarium moniliforme, Pseudomonas, TNF-alpha

Procedia PDF Downloads 185
11 Resveratrol Ameliorates Benzo(a)Pyrene Induced Testicular Dysfunction and Apoptosis: Involvement of p38 MAPK/ATF2/iNOS Signaling

Authors: Kuladip Jana, Bhaswati Banerjee, Parimal C. Sen

Abstract:

Benzo(a)pyrene [B(a)P] is an environmental toxicant present mostly in cigarette smoke and car exhaust, is an aryl hydrocarbon receptor (AhR) ligand that exerts its toxic effects on both male and female reproductive systems along with carcinogenesis in skin, prostate, ovary, lung and mammary glands. Our study was focused on elucidating the molecular mechanism of B(a)P induced male reproductive toxicity and its prevention with phytochemical like resveratrol. In this study, the effect of B(a)P at different doses (0.1, 0.25, 0.5, 1 and 5 mg /kg body weight) was studied on male reproductive system of Wistar rat. A significant decrease in cauda epididymal sperm count and motility along with the presence of sperm head abnormalities and altered epididymal and testicular histology were documented following B(a)P treatment. B(a)P treatment resulted apoptotic sperm cells as observed by TUNEL and Annexin V-PI assay with increased Reactive Oxygen Species (ROS), altered sperm mitochondrial membrane potential (ΔΨm) with a simultaneous decrease in the activity of antioxidant enzymes and GSH status. TUNEL positive apoptotic cells also observed in testis as well as isolated germ and Leydig cells following B(a)P exposure. Western Blot analysis revealed the activation of p38 mitogen activated protein kinase (p38MAPK), cytosolic translocation of cytochrome-c, upregulation of Bax and inducible nitric oxide synthase (iNOS) with cleavage of poly ADP ribose polymerase (PARP) and down regulation of BCl2 in testis upon B(a)P treatment. The protein and mRNA levels of testicular key steroidogenesis regulatory proteins like steroidogenic acute regulatory protein (StAR), cytochrome P450 IIA1 (CYPIIA1), 3β hydroxy steroid dehydrogenase (3β HSD), 17β hydroxy steroid dehydrogenase (17β HSD) showed a significant decrease in a dose dependent manner while an increase in the expression of cytochrome P450 1A1 (CYP1A1), Aryl hydrocarbon Receptor (AhR), active caspase- 9 and caspase- 3 following B(a)P exposure. We conclude that exposure of benzo(a)pyrene caused testicular gamatogenic and steroidogenic disorders by induction of oxidative stress, inhibition of StAR and other steroidogenic enzymes along with activation of p38MAPK and initiated caspase-3 mediated germ and Leydig cell apoptosis. Next we investigated the role of resveratrol on B(a)P induced male reproductive toxicity. Our study highlighted that resveratrol co-treatment with B(a)P maintained testicular redox potential, increased serum testosterone level and prevented steroidogenic dysfunction with enhanced expression of major testicular steroidogenic proteins (CYPIIA1, StAR, 3β HSD,17β HSD) relative to treatment with B(a)P only. Resveratrol suppressed B(a)P-induced testicular activation of p38 MAPK, ATF2, iNOS and ROS production; cytosolic translocation of Cytochome c and Caspase 3 activation thereby prevented oxidative stress of testis and inhibited apoptosis. Resveratrol co-treatment also decreased B(a)P-induced AhR protein level, its nuclear translocation and subsequent CYP1A1 promoter activation, thereby decreased protein and mRNA levels of testicular cytochrome P4501A1 (CYP1A1) and prevented BPDE-DNA adduct formation. Our findings cumulatively suggest that resveratrol prevents activation of B(a)P by modulating the transcriptional regulation of CYP1A1 and acting as an antioxidant thus prevents B(a)P-induced oxidative stress and testicular apoptosis.

Keywords: benzo(a)pyrene, resveratrol, testis, apoptosis, cytochrome P450 1A1 (CYP1A1), aryl hydrocarbon receptor (AhR), p38 MAPK/ATF2/iNOS

Procedia PDF Downloads 200
10 Musictherapy and Gardentherapy: A Systemic Approach for the Life Quality of the PsychoPhysical Disability

Authors: Adriana De Serio, Donato Forenza

Abstract:

Aims. In this experimental research the Authors present the methodological plan “Musictherapy and Gardentherapy” that they created interconnected with the garden landscape ecosystems and aimed at PsychoPhysical Disability (MusGarPPhyD). In the context of the environmental education aimed at spreading the landscape culture and its values, it’s necessary to develop a solid perception of the environment sustainability to implement a multidimensional approach that pays attention to the conservation and enhancement of gardens and natural environments. The result is an improvement in the life quality also in compliance with the objectives of the European Agenda 2030. The MusGarPPhyD can help professionals such as musictherapists and environmental and landscape researchers strengthen subjects' motivation to learn to deal with the psychophysical discomfort associated with disability and to cope with the distress and the psychological fragility and the loneliness and the social seclusion and to promote productive social relationships. Materials and Methods. The MusGarPPhyD was implemented in multiple spaces. The musictherapy treatments took place first inside residential therapeutic centres and then in the garden landscape ecosystem. Patients: twenty, set in two groups. Weekly-sessions (50’) for three months. Methodological phases: - Phase P1. MusicTherapy treatments for each group in the indoor spaces. - Phase P2. MusicTherapy sessions inside the gardens. After each Phase, P1 and P2: - a Questionnaire for each patient (ten items / liking-indices) was administrated at t0 time, during the treatment and at tn time at the end of the treatment. - Monitoring of patients' behavioral responses through assessment scales, matrix, table and graph system. MusicTherapy methodology: pazient Sonorous-Musical Anamnesis, Musictherapy Assessment Document, Observation Protocols, Bodily-Environmental-Rhythmical-Sonorous-Vocal-Energy production first indoors and then outside, sonorous-musical instruments and edible instruments made by the Author/musictherapist with some foods; Administration of Patient-Environment-Music Index at time to and tn, to estimate the patient’s behavior evolution, Musictherapeutic Advancement Index. Results. The MusGarPPhyD can strengthen the individual sense of identity and improve the psychophysical skills and the resilience to face and to overcome the difficulties caused by the congenital /acquired disability. The multi-sensory perceptions deriving from contact with the plants in the gardens improve the psychological well-being and regulate the physiological parameters such as blood pressure, cardiac and respiratory rhythm, reducing the cholesterol levels. The secretions of the peptide hormones endorphins and the endogenous opioids enkephalins increase and bring a state of patient’s tranquillity and a better mood. The subjects showed a preference for musictherapy treatments within a setting made up of gardens and peculiar landscape systems. This resulted in greater health benefits. Conclusions. The MusGarPPhyD contributes to reduce psychophysical tensions, anxiety, depression and stress, facilitating the connections between the cerebral hemispheres, thus also improving intellectual performances, self-confidence, motor skills and social interactions. Therefore it is necessary to design hospitals, rehabilitation centers, nursing homes, surrounded by gardens. Ecosystems of natural and urban parks and gardens create fascinating skyline and mosaics of landscapes rich in beauty and biodiversity. The MusGarPPhyD is useful for the health management promoting patient’s psychophysical activation, better mood/affective-tone and relastionships and contributing significantly to improving the life quality.

Keywords: musictherapy, gardentherapy, disability, life quality

Procedia PDF Downloads 41
9 Identification Strategies for Unknown Victims from Mass Disasters and Unknown Perpetrators from Violent Crime or Terrorist Attacks

Authors: Michael Josef Schwerer

Abstract:

Background: The identification of unknown victims from mass disasters, violent crimes, or terrorist attacks is frequently facilitated through information from missing persons lists, portrait photos, old or recent pictures showing unique characteristics of a person such as scars or tattoos, or simply reference samples from blood relatives for DNA analysis. In contrast, the identification or at least the characterization of an unknown perpetrator from criminal or terrorist actions remains challenging, particularly in the absence of material or data for comparison, such as fingerprints, which had been previously stored in criminal records. In scenarios that result in high levels of destruction of the perpetrator’s corpse, for instance, blast or fire events, the chance for a positive identification using standard techniques is further impaired. Objectives: This study shows the forensic genetic procedures in the Legal Medicine Service of the German Air Force for the identification of unknown individuals, including such cases in which reference samples are not available. Scenarios requiring such efforts predominantly involve aircraft crash investigations, which are routinely carried out by the German Air Force Centre of Aerospace Medicine as one of the Institution’s essential missions. Further, casework by military police or military intelligence is supported based on administrative cooperation. In the talk, data from study projects, as well as examples from real casework, will be demonstrated and discussed with the audience. Methods: Forensic genetic identification in our laboratories involves the analysis of Short Tandem Repeats and Single Nucleotide Polymorphisms in nuclear DNA along with mitochondrial DNA haplotyping. Extended DNA analysis involves phenotypic markers for skin, hair, and eye color together with the investigation of a person’s biogeographic ancestry. Assessment of the biological age of an individual employs CpG-island methylation analysis using bisulfite-converted DNA. Forensic Investigative Genealogy assessment allows the detection of an unknown person’s blood relatives in reference databases. Technically, end-point-PCR, real-time PCR, capillary electrophoresis, pyrosequencing as well as next generation sequencing using flow-cell-based and chip-based systems are used. Results and Discussion: Optimization of DNA extraction from various sources, including difficult matrixes like formalin-fixed, paraffin-embedded tissues, degraded specimens from decomposed bodies or from decedents exposed to blast or fire events, provides soil for successful PCR amplification and subsequent genetic profiling. For cases with extremely low yields of extracted DNA, whole genome preamplification protocols are successfully used, particularly regarding genetic phenotyping. Improved primer design for CpG-methylation analysis, together with validated sampling strategies for the analyzed substrates from, e.g., lymphocyte-rich organs, allows successful biological age estimation even in bodies with highly degraded tissue material. Conclusions: Successful identification of unknown individuals or at least their phenotypic characterization using pigmentation markers together with age-informative methylation profiles, possibly supplemented by family tree search employing Forensic Investigative Genealogy, can be provided in specialized laboratories. However, standard laboratory procedures must be adapted to work with difficult and highly degraded sample materials.

Keywords: identification, forensic genetics, phenotypic markers, CPG methylation, biological age estimation, forensic investigative genealogy

Procedia PDF Downloads 23
8 Turn Organic Waste to Green Fuels with Zero Landfill

Authors: Xu Fei (Philip) WU

Abstract:

As waste recycling concept been accepted more and more in modern societies, the organic portion of the municipal waste become a sires issue in today’s life. Depend on location and season, the organic waste can bee anywhere between 40-65% of total municipal solid waste. Also composting and anaerobic digestion technologies been applied in this field for years, however both process have difficulties been selected by economical and environmental factors. Beside environmental pollution and risk of virus spread, the compost is not a product been welcomed by people even the waste management has to give up them at no cost. The anaerobic digester has to have 70% of water and keep at 35 degree C or above; base on above conditions, the retention time only can be up to two weeks and remain solid has to be dewater and composting again. The enhancive waste water treatment has to be added after. Because these reasons, the voice of suggesting cancelling recycling program and turning all waste to mass burn incinerations have been raised-A process has already been proved has least energy efficiency and most air pollution problem associated process. A newly developed WXF Bio-energy process employs recently developed and patented pre-designed separation, multi-layer and multi-cavity successive bioreactor landfill technology. It features an improved leachate recycling technology, technologies to maximize the biogas generation rate and a reduced overall turnaround period on the land. A single properly designed and operated site can be used indefinitely. In this process, all collected biogas will be processed to eliminate H2S and other hazardous gases. The methane, carbon dioxide and hydrogen will be utilized in a proprietary process to manufacture methanol which can be sold to mitigate operating costs of the landfill. This integration of new processes offers a more advanced alternative to current sanitary landfill, incineration and compost technology. Xu Fei (Philip) Wu Xu Fei Wu is founder and Chief Scientist of W&Y Environmental International Inc. (W & Y), a Canadian environmental and sustainable energy technology company with patented landfill processes and proprietary waste to energy technologies. He has worked in environmental and sustainable energy fields over the last 25 years. Before W&Y, he worked for Conestoga-Rovers & Associates Limited, Microbe Environmental Science and Technology Inc. of Canada and The Ministry of Nuclear Industry and Ministry of Space Flight Industry of China. Xu Fei Wu holds a Master of Engineering Science degree from The University of Western Ontario. I wish present this paper as an oral presentation only Selected Conference Presentations: • “Removal of Phenolic Compounds with Algae” Presented at 25th Canadian Symposium on Water Pollution Research (CAWPRC Conference), Burlington, Ontario Canada. February, 1990 • “Removal of Phenolic Compounds with Algae” Presented at Annual Conference of Pollution Control Association of Ontario, London, Ontario, Canada. April, 1990 • “Removal of Organochlorine Compounds in a Flocculated Algae Photo-Bioreactor” Presented at International Symposium on Low Cost and Energy Saving Wastewater Treatment Technologies (IAWPRC Conference), Kiyoto, Japan, August, 1990 • “Maximizing Production and Utilization of Landfill Gas” 2009 Wuhan International Conference on Environment(CAWPRC Conference, sponsored by US EPA) Wuhan, China. October, 2009. • “WXF Bio-Energy-A Green, Sustainable Waste to Energy Process” Presented at 9Th International Conference Cooperation for Waste Issues, Kharkiv, Ukraine March, 2012 • “A Lannfill Site Can Be Recycled Indefinitely” Presented at 28th International Conference on solid Waste Technology and Management, Philadelphia, Pennsylvania, USA. March, 2013. Hosted by The Journal of Solid Waste Technology and Management.

Keywords: green fuel, waste management, bio-energy, sustainable development, methanol

Procedia PDF Downloads 248
7 Developing a Place-Name Gazetteer for Singapore by Mining Historical Planning Archives and Selective Crowd-Sourcing

Authors: Kevin F. Hsu, Alvin Chua, Sarah X. Lin

Abstract:

As a multilingual society, Singaporean names for different parts of the city have changed over time. Residents included Indigenous Malays, dialect-speakers from China, European settler-colonists, and Tamil-speakers from South India. Each group would name locations in their own languages. Today, as ancestral tongues are increasingly supplanted by English, contemporary Singaporeans’ understanding of once-common place names is disappearing. After demolition or redevelopment, some urban places will only exist in archival records or in human memory. United Nations conferences on the standardization of geographic names have called attention to how place names relate to identity, well-being, and a sense of belonging. The Singapore Place-Naming Project responds to these imperatives by capturing past and present place names through digitizing historical maps, mining archival records, and applying selective crowd-sourcing to trace the evolution of place names throughout the city. The project ensures that both formal and vernacular geographical names remain accessible to historians, city planners, and the public. The project is compiling a gazetteer, a geospatial archive of placenames, with streets, buildings, landmarks, and other points of interest (POI) appearing in the historic maps and planning documents of Singapore, currently held by the National Archives of Singapore, the National Library Board, university departments, and the Urban Redevelopment Authority. To create a spatial layer of information, the project links each place name to either a geo-referenced point, line segment, or polygon, along with the original source material in which the name appears. This record is supplemented by crowd-sourced contributions from civil service officers and heritage specialists, drawing from their collective memory to (1) define geospatial boundaries of historic places that appear in past documents, but maybe unfamiliar to users today, and (2) identify and record vernacular place names not captured in formal planning documents. An intuitive interface allows participants to demarcate feature classes, vernacular phrasings, time periods, and other knowledge related to historical or forgotten spaces. Participants are stratified into age bands and ethnicity to improve representativeness. Future iterations could allow additional public contributions. Names reveal meanings that communities assign to each place. While existing historical maps of Singapore allow users to toggle between present-day and historical raster files, this project goes a step further by adding layers of social understanding and planning documents. Tracking place names illuminates linguistic, cultural, commercial, and demographic shifts in Singapore, in the context of transformations of the urban environment. The project also demonstrates how a moderated, selectively crowd-sourced effort can solicit useful geospatial data at scale, sourced from different generations, and at higher granularity than traditional surveys, while mitigating negative impacts of unmoderated crowd-sourcing. Stakeholder agencies believe the project will achieve several objectives, including Supporting heritage conservation and public education; Safeguarding intangible cultural heritage; Providing historical context for street, place or development-renaming requests; Enhancing place-making with deeper historical knowledge; Facilitating emergency and social services by tagging legal addresses to vernacular place names; Encouraging public engagement with heritage by eliciting multi-stakeholder input.

Keywords: collective memory, crowd-sourced, digital heritage, geospatial, geographical names, linguistic heritage, place-naming, Singapore, Southeast Asia

Procedia PDF Downloads 95
6 MANIFEST-2, a Global, Phase 3, Randomized, Double-Blind, Active-Control Study of Pelabresib (CPI-0610) and Ruxolitinib vs. Placebo and Ruxolitinib in JAK Inhibitor-Naïve Myelofibrosis Patients

Authors: Claire Harrison, Raajit K. Rampal, Vikas Gupta, Srdan Verstovsek, Moshe Talpaz, Jean-Jacques Kiladjian, Ruben Mesa, Andrew Kuykendall, Alessandro Vannucchi, Francesca Palandri, Sebastian Grosicki, Timothy Devos, Eric Jourdan, Marielle J. Wondergem, Haifa Kathrin Al-Ali, Veronika Buxhofer-Ausch, Alberto Alvarez-Larrán, Sanjay Akhani, Rafael Muñoz-Carerras, Yury Sheykin, Gozde Colak, Morgan Harris, John Mascarenhas

Abstract:

Myelofibrosis (MF) is characterized by bone marrow fibrosis, anemia, splenomegaly and constitutional symptoms. Progressive bone marrow fibrosis results from aberrant megakaryopoeisis and expression of proinflammatory cytokines, both of which are heavily influenced by bromodomain and extraterminal domain (BET)-mediated gene regulation and lead to myeloproliferation and cytopenias. Pelabresib (CPI-0610) is an oral small-molecule investigational inhibitor of BET protein bromodomains currently being developed for the treatment of patients with MF. It is designed to downregulate BET target genes and modify nuclear factor kappa B (NF-κB) signaling. MANIFEST-2 was initiated based on data from Arm 3 of the ongoing Phase 2 MANIFEST study (NCT02158858), which is evaluating the combination of pelabresib and ruxolitinib in Janus kinase inhibitor (JAKi) treatment-naïve patients with MF. Primary endpoint analyses showed splenic and symptom responses in 68% and 56% of 84 enrolled patients, respectively. MANIFEST-2 (NCT04603495) is a global, Phase 3, randomized, double-blind, active-control study of pelabresib and ruxolitinib versus placebo and ruxolitinib in JAKi treatment-naïve patients with primary MF, post-polycythemia vera MF or post-essential thrombocythemia MF. The aim of this study is to evaluate the efficacy and safety of pelabresib in combination with ruxolitinib. Here we report updates from a recent protocol amendment. The MANIFEST-2 study schema is shown in Figure 1. Key eligibility criteria include a Dynamic International Prognostic Scoring System (DIPSS) score of Intermediate-1 or higher, platelet count ≥100 × 10^9/L, spleen volume ≥450 cc by computerized tomography or magnetic resonance imaging, ≥2 symptoms with an average score ≥3 or a Total Symptom Score (TSS) of ≥10 using the Myelofibrosis Symptom Assessment Form v4.0, peripheral blast count <5% and Eastern Cooperative Oncology Group performance status ≤2. Patient randomization will be stratified by DIPSS risk category (Intermediate-1 vs Intermediate-2 vs High), platelet count (>200 × 10^9/L vs 100–200 × 10^9/L) and spleen volume (≥1800 cm^3 vs <1800 cm^3). Double-blind treatment (pelabresib or matching placebo) will be administered once daily for 14 consecutive days, followed by a 7 day break, which is considered one cycle of treatment. Ruxolitinib will be administered twice daily for all 21 days of the cycle. The primary endpoint is SVR35 response (≥35% reduction in spleen volume from baseline) at Week 24, and the key secondary endpoint is TSS50 response (≥50% reduction in TSS from baseline) at Week 24. Other secondary endpoints include safety, pharmacokinetics, changes in bone marrow fibrosis, duration of SVR35 response, duration of TSS50 response, progression-free survival, overall survival, conversion from transfusion dependence to independence and rate of red blood cell transfusion for the first 24 weeks. Study recruitment is ongoing; 400 patients (200 per arm) from North America, Europe, Asia and Australia will be enrolled. The study opened for enrollment in November 2020. MANIFEST-2 was initiated based on data from the ongoing Phase 2 MANIFEST study with the aim of assessing the efficacy and safety of pelabresib and ruxolitinib in JAKi treatment-naïve patients with MF. MANIFEST-2 is currently open for enrollment.

Keywords: CPI-0610, JAKi treatment-naïve, MANIFEST-2, myelofibrosis, pelabresib

Procedia PDF Downloads 167
5 An Intelligent Search and Retrieval System for Mining Clinical Data Repositories Based on Computational Imaging Markers and Genomic Expression Signatures for Investigative Research and Decision Support

Authors: David J. Foran, Nhan Do, Samuel Ajjarapu, Wenjin Chen, Tahsin Kurc, Joel H. Saltz

Abstract:

The large-scale data and computational requirements of investigators throughout the clinical and research communities demand an informatics infrastructure that supports both existing and new investigative and translational projects in a robust, secure environment. In some subspecialties of medicine and research, the capacity to generate data has outpaced the methods and technology used to aggregate, organize, access, and reliably retrieve this information. Leading health care centers now recognize the utility of establishing an enterprise-wide, clinical data warehouse. The primary benefits that can be realized through such efforts include cost savings, efficient tracking of outcomes, advanced clinical decision support, improved prognostic accuracy, and more reliable clinical trials matching. The overarching objective of the work presented here is the development and implementation of a flexible Intelligent Retrieval and Interrogation System (IRIS) that exploits the combined use of computational imaging, genomics, and data-mining capabilities to facilitate clinical assessments and translational research in oncology. The proposed System includes a multi-modal, Clinical & Research Data Warehouse (CRDW) that is tightly integrated with a suite of computational and machine-learning tools to provide insight into the underlying tumor characteristics that are not be apparent by human inspection alone. A key distinguishing feature of the System is a configurable Extract, Transform and Load (ETL) interface that enables it to adapt to different clinical and research data environments. This project is motivated by the growing emphasis on establishing Learning Health Systems in which cyclical hypothesis generation and evidence evaluation become integral to improving the quality of patient care. To facilitate iterative prototyping and optimization of the algorithms and workflows for the System, the team has already implemented a fully functional Warehouse that can reliably aggregate information originating from multiple data sources including EHR’s, Clinical Trial Management Systems, Tumor Registries, Biospecimen Repositories, Radiology PAC systems, Digital Pathology archives, Unstructured Clinical Documents, and Next Generation Sequencing services. The System enables physicians to systematically mine and review the molecular, genomic, image-based, and correlated clinical information about patient tumors individually or as part of large cohorts to identify patterns that may influence treatment decisions and outcomes. The CRDW core system has facilitated peer-reviewed publications and funded projects, including an NIH-sponsored collaboration to enhance the cancer registries in Georgia, Kentucky, New Jersey, and New York, with machine-learning based classifications and quantitative pathomics, feature sets. The CRDW has also resulted in a collaboration with the Massachusetts Veterans Epidemiology Research and Information Center (MAVERIC) at the U.S. Department of Veterans Affairs to develop algorithms and workflows to automate the analysis of lung adenocarcinoma. Those studies showed that combining computational nuclear signatures with traditional WHO criteria through the use of deep convolutional neural networks (CNNs) led to improved discrimination among tumor growth patterns. The team has also leveraged the Warehouse to support studies to investigate the potential of utilizing a combination of genomic and computational imaging signatures to characterize prostate cancer. The results of those studies show that integrating image biomarkers with genomic pathway scores is more strongly correlated with disease recurrence than using standard clinical markers.

Keywords: clinical data warehouse, decision support, data-mining, intelligent databases, machine-learning.

Procedia PDF Downloads 91
4 The Impact of the Macro-Level: Organizational Communication in Undergraduate Medical Education

Authors: Julie M. Novak, Simone K. Brennan, Lacey Brim

Abstract:

Undergraduate medical education (UME) curriculum notably addresses micro-level communications (e.g., patient-provider, intercultural, inter-professional), yet frequently under-examines the role and impact of organizational communication, a more macro-level. Organizational communication, however, functions as foundation and through systemic structures of an organization and thereby serves as hidden curriculum and influences learning experiences and outcomes. Yet, little available research exists fully examining how students experience organizational communication while in medical school. Extant literature and best practices provide insufficient guidance for UME programs, in particular. The purpose of this study was to map and examine current organizational communication systems and processes in a UME program. Employing a phenomenology-grounded and participatory approach, this study sought to understand the organizational communication system from medical students' perspective. The research team consisted of a core team and 13 medical student co-investigators. This research employed multiple methods, including focus groups, individual interviews, and two surveys (one reflective of focus group questions, the other requesting students to submit ‘examples’ of communications). To provide context for student responses, nonstudent participants (faculty, administrators, and staff) were sampled, as they too express concerns about communication. Over 400 students across all cohorts and 17 nonstudents participated. Data were iteratively analyzed and checked for triangulation. Findings reveal the complex nature of organizational communication and student-oriented communications. They reveal program-impactful strengths, weaknesses, gaps, and tensions and speak to the role of organizational communication practices influencing both climate and culture. With regard to communications, students receive multiple, simultaneous communications from multiple sources/channels, both formal (e.g., official email) and informal (e.g., social media). Students identified organizational strengths including the desire to improve student voice, and message frequency. They also identified weaknesses related to over-reliance on emails, numerous platforms with inconsistent utilization, incorrect information, insufficient transparency, assessment/input fatigue, tacit expectations, scheduling/deadlines, responsiveness, and mental health confidentiality concerns. Moreover, they noted gaps related to lack of coordination/organization, ambiguous point-persons, student ‘voice-only’, open communication loops, lack of core centralization and consistency, and mental health bridges. Findings also revealed organizational identity and cultural characteristics as impactful on the medical school experience. Cultural characteristics included program size, diversity, urban setting, student organizations, community-engagement, crisis framing, learning for exams, inefficient bureaucracy, and professionalism. Moreover, they identified system structures that do not always leverage cultural strengths or reduce cultural problematics. Based on the results, opportunities for productive change are identified. These include leadership visibly supporting and enacting overall organizational narratives, making greater efforts in consistently ‘closing the loop’, regularly sharing how student input effects change, employing strategies of crisis communication more often, strengthening communication infrastructure, ensuring structures facilitate effective operations and change efforts, and highlighting change efforts in informational communication. Organizational communication and communications are not soft-skills, or of secondary concern within organizations, rather they are foundational in nature and serve to educate/inform all stakeholders. As primary stakeholders, students and their success directly affect the accomplishment of organizational goals. This study demonstrates how inquiries about how students navigate their educational experience extends research-based knowledge and provides actionable knowledge for the improvement of organizational operations in UME.

Keywords: medical education programs, organizational communication, participatory research, qualitative mixed methods

Procedia PDF Downloads 95
3 “MaxSALIVA-II” Advancing a Nano-Sized Dual-Drug Delivery System for Salivary Gland Radioprotection, Regeneration and Repair in a Head and Neck Cancer Pre-Clinical Murine Model

Authors: Ziyad S. Haidar

Abstract:

Background: Saliva plays a major role in maintaining oral, dental, and general health and well-being; where it normally bathes the oral cavity acting as a clearing agent. This becomes more apparent when the amount and quality of saliva are significantly reduced due to medications, salivary gland neoplasms, disorders such as Sjögren’s syndrome, and especially ionizing radiation therapy for tumors of the head and neck, the 5th most common malignancy worldwide, during which the salivary glands are included within the radiation field/zone. Clinically, patients affected by salivary gland dysfunction often opt to terminate their radiotherapy course prematurely as they become malnourished and experience a significant decrease in their QoL. Accordingly, the formulation of a radio-protection/-prevention modality and development of an alternative Rx to restore damaged salivary gland tissue is eagerly awaited and highly desirable. Objectives: Assess the pre-clinical radio-protective effect and reparative/regenerative potential of layer-by-layer self-assembled lipid-polymer-based core-shell nanocapsules designed and fine-tuned for the sequential (ordered) release of dual cytokines, following a single local administration (direct injection) into a murine sub-mandibular salivary gland model of irradiation. Methods: The formulated core-shell nanocapsules were characterized by physical-chemical-mechanically pre-/post-loading with the drugs, followed by optimizing the pharmaco-kinetic profile. Then, nanosuspensions were administered directly into the salivary glands, 24hrs pre-irradiation (PBS, un-loaded nanocapsules, and individual and combined vehicle-free cytokines were injected into the control glands for an in-depth comparative analysis). External irradiation at an elevated dose of 18Gy was exposed to the head-and-neck region of C57BL/6 mice. Salivary flow rate (un-stimulated) and salivary protein content/excretion were regularly assessed using an enzyme-linked immunosorbent assay (3-month period). Histological and histomorphometric evaluation and apoptosis/proliferation analysis followed by local versus systemic bio-distribution and immuno-histochemical assays were then performed on all harvested major organs (at the distinct experimental end-points). Results: Monodisperse, stable, and cytocompatible nanocapsules capable of maintaining the bioactivity of the encapsulant within the different compartments with the core and shell and with controlled/customizable pharmaco-kinetics, resulted, as is illustrated in the graphical abstract (Figure) below. The experimental animals demonstrated a significant increase in salivary flow rates when compared to the controls. Herein, salivary protein content was comparable to the pre-irradiation (baseline) level. Histomorphometry further confirmed the biocompatibility and localization of the nanocapsules, in vivo, into the site of injection. Acinar cells showed fewer vacuoles and nuclear aberration in the experimental group, while the amount of mucin was higher in controls. Overall, fewer apoptotic activities were detected by a Terminal deoxynucleotidyl Transferase (TdT) dUTP Nick-End Labeling (TUNEL) assay and proliferative rates were similar to the controls, suggesting an interesting reparative and regenerative potential of irradiation-damaged/-dysfunctional salivary glands. The Figure below exemplifies some of these findings. Conclusions: Biocompatible, reproducible, and customizable self-assembling layer-by-layer core-shell delivery system is formulated and presented. Our findings suggest that localized sequential bioactive delivery of dual cytokines (in specific dose and order) can prevent irradiation-induced damage via reducing apoptosis and also has the potential to promote in situ proliferation of salivary gland cells; maxSALIVA is scalable (Good Manufacturing Practice or GMP production for human clinical trials) and patent-pending.

Keywords: cancer, head and neck, oncology, drug development, drug delivery systems, nanotechnology, nanoncology

Procedia PDF Downloads 54
2 Glycyrrhizic Acid Inhibits Lipopolysaccharide-Stimulated Bovine Fibroblast-Like Synoviocyte, Invasion through Suppression of TLR4/NF-κB-Mediated Matrix Metalloproteinase-9 Expression

Authors: Hosein Maghsoudi

Abstract:

Rheumatois arthritis (RA) is progressive inflammatory autoimmune diseases that primarily affect the joints, characterized by synovial hyperplasia and inflammatory cell infiltration, deformed and painful joints, which can lead tissue destruction, functional disability systemic complications, and early dead and socioeconomic costs. The cause of rheumatoid arthritis is unknown, but genetic and environmental factors are contributory and the prognosis is guarded. However, advances in understanding the pathogenesis of the disease have fostered the development of new therapeutics, with improved outcomes. The current treatment strategy, which reflects this progress, is to initiate aggressive therapy soon after diagnosis and to escalate the therapy, guided by an assessment of disease activity, in pursuit of clinical remission. The pathobiology of RA is multifaceted and involves T cells, B cells, fibroblast-like synoviocyte (FLSc) and the complex interaction of many pro-inflammatory cytokine. Novel biologic agents that target tumor necrosis or interlukin (IL)-1 and Il-6, in addition T- and B-cells inhibitors, have resulted in favorable clinical outcomes in patients with RA. Despite this, at least 30% of RA patients are résistance to available therapies, suggesting novel mediators should be identified that can target other disease-specific pathway or cell lineage. Among the inflammatory cell population that might participated in RA pathogenesis, FLSc are crucial in initiaing and driving RA in concert of cartilage and bone by secreting metalloproteinase (MMPs) into the synovial fluid and by direct invasion into extracellular matrix (ECM), further exacerbating joint damage. Invasion of fibroblast-like synoviocytes (FLSc) is critical in the pathogenesis of rheumatoid-arthritis. The metalloproteinase (MMPs) and activator of Toll-like receptor 4 (TLR4)/nuclear factor- κB pthway play a critical role in RA-FLS invasion induced by lipopolysaccharide (LPS). The present study aimed to explore the anti-invasion activity of Glycyrrhizic Acid as a pharmacologically safe phytochemical agent with potent anti-inflammatory properties on IL-1beta and TNF-alpha signalling pathways in Bovine fibroblast-like synoviocyte ex- vitro, on LPS-stimulated bovine FLS migration and invasion as well as MMP expression and explored the upstream signal transduction. Results showed that Glycyrrhizic Acid suppressed LPS-stimulated bovine FLS migration and invasion by inhibition MMP-9 expression and activity. In addition our results revealed that Glycyrrhizic Acid inhibited the transcriptional activity of MMP-9 by suppression the nbinding activity of NF- κB in the MMP-9 promoter pathway. The extract of licorice (Glycyrrhiza glabra L.) has been widely used for many centuries in the traditional Chinese medicine as native anti-allergic agent. Glycyrrhizin (GL), a triterpenoidsaponin, extracted from the roots of licorice is the most effective compound for inflammation and allergic diseases in human body. The biological and pharmacological studies revealed that GL possesses many pharmacological effects, such as anti-inflammatory, anti-viral and liver protective effects, and the biological effects, such as induction of cytokines (interferon-γ and IL-12), chemokines as well as extrathymic T and anti-type 2 T cells. GL is known in the traditional Chinese medicine for its anti-inflammatory effect, which is originally described by Finney in 1959. The mechanism of the GL-induced anti-inflammatory effect is based on different pathways of the GL-induced selective inhibition of the prostaglandin E2 production, the CK-II- mediated activation of both GL-binding lipoxygenas (gbLOX; 17) and PLA2, an anti-thrombin action of GL and production of the reactive oxygen species (ROS; GL exerts liver protection properties by inhibiting PLA2 or by the hydroxyl radical trapping action, leading to the lowering of serum alanine and aspartate transaminase levels. The present study was undertaken to examine the possible mechanism of anti-inflammatory properties GL on IL-1beta and TNF-alpha signalling pathways in bovine fibroblast-like synoviocyte ex-vivo, on LPS-stimulated bovine FLS migration and invasion as well as MMP expression and explored the upstream signal transduction. Our results clearly showed that treatment of bovine fibroblast-like synoviocyte with GL suppressed LPS-induced cell migration and invasion. Furthermore, it revealed that GL inhibited the transcription activity of MMP-9 by suppressing the binding activity of NF-κB in the MM-9 promoter. MMP-9 is an important ECM-degrading enzyme and overexpression of MMPs in important of RA-FLSs. LPS can stimulate bovine FLS to secret MMPs, and this induction is regulated at the transcription and translational levels. In this study, LPS treatment of bovine FLS caused an increase in MMP-2 and MMP-9 levels. The increase in MMP-9 expression and secretion was inhibited by ex- vitro. Furthermore, these effects were mimicked by MMP-9 siRNA. These result therefore indicate the the inhibition of LPS-induced bovine FLS invasion by GL occurs primarily by inhibiting MMP-9 expression and activity. Next we analyzed the functional significance of NF-κB transcription of MMP-9 activation in Bovine FLSs. Results from EMSA showed that GL suppressed LPS-induced NF-κB binding to the MMP-9 promotor, as NF-κB regulates transcriptional activation of multiple inflammatory cytokines, we predicted that GL might target NF-κB to suppress MMP-9 transcription by LPS. Myeloid differentiation-factor 88 (MyD88) and TIR-domain containing adaptor protein (TIRAP) are critical proteins in the LPS-induced NF-κB and apoptotic signaling pathways, GL inhibited the expression of TLR4 and MYD88. These results demonstrated that GL suppress LPS-induced MMP-9 expression through the inhibition of the induced TLR4/NFκB signaling pathway. Taken together, our results provide evidence that GL exerts anti-inflammatory effects by inhibition LPS-induced bovine FLSs migration and invasion, and the mechanisms may involve the suppression of TLR4/NFκB –mediated MMP-9 expression. Although further work is needed to clarify the complicated mechanism of GL-induced anti-invasion of bovine FLSs, GL might be used as a further anti-invasion drug with therapeutic efficacy in the treatment of immune-mediated inflammatory disease such as RA.

Keywords: glycyrrhizic acid, bovine fibroblast-like synoviocyte, tlr4/nf-κb, metalloproteinase-9

Procedia PDF Downloads 362
1 “MaxSALIVA”: A Nano-Sized Dual-Drug Delivery System for Salivary Gland Radioprotection and Repair in Head and Neck Cancer

Authors: Ziyad S. Haidar

Abstract:

Background: Saliva plays a major role in maintaining oral and dental health (consequently, general health and well-being). Where it normally bathes the oral cavity and acts as a clearing agent. This becomes more apparent when the amount and quality of salivare significantly reduced due to medications, salivary gland neoplasms, disorders such as Sjögren’s syndrome, and especially ionizing radiation therapy for tumors of the head and neck, the fifth most common malignancy worldwide, during which the salivary glands are included within the radiation field or zone. Clinically, patients affected by salivary gland dysfunction often opt to terminate their radiotherapy course prematurely because they become malnourished and experience a significant decrease in their quality of life. Accordingly, the development of an alternative treatment to restore or regenerate damaged salivary gland tissue is eagerly awaited. Likewise, the formulation of a radioprotection modality and early damage prevention strategy is also highly desirable. Objectives: To assess the pre-clinical radio-protective effect as well as the reparative/regenerative potential of layer-by-layer self-assembled lipid-polymer-based core-shell nanocapsules designed and fine-tuned in this experimental work for the sequential (ordered) release of dual cytokines, following a single local administration (direct injection) into a murine sub-mandibular salivary gland model of irradiation. Methods: The formulated core-shell nanocapsules were characterized by physical-chemical-mechanically pre-/post-loading with the drugs (in solution and powder formats), followed by optimizing the pharmaco-kinetic profile. Then, nanosuspensions were administered directly into the salivary glands, 24hrs pre-irradiation (PBS, un-loaded nanocapsules, and individual and combined vehicle-free cytokines were injected into the control glands for an in-depth comparative analysis). External irradiation at an elevated dose of 18Gy (revised from our previous 15Gy model) was exposed to the head-and-neck region of C57BL/6 mice. Salivary flow rate (un-stimulated) and salivary protein content/excretion were regularly assessed using an enzyme-linked immunosorbent assay (3-month period). Histological and histomorphometric evaluation and apoptosis/proliferation analysis followed by local versus systemic bio-distribution and immuno-histochemical assays were then performed on all harvested major organs (at the distinct experimental end-points). Results: Monodisperse, stable, and cytocompatible nanocapsules capable of maintaining the bioactivity of the encapsulant within the different compartments with the core and shell and with controlled/customizable pharmaco-kinetics, resulted, as is illustrated in the graphical abstract (Figure) below. The experimental animals demonstrated a significant increase in salivary flow rates when compared to the controls. Herein, salivary protein content was comparable to the pre-irradiation (baseline) level. Histomorphometry further confirmed the biocompatibility and localization of the nanocapsules, in vivo, into the site of injection. Acinar cells showed fewer vacuoles and nuclear aberration in the experimental group, while the amount of mucin was higher in controls. Overall, fewer apoptotic activities were detected by a Terminal deoxynucleotidyl Transferase (TdT) dUTP Nick-End Labeling (TUNEL) assay and proliferative rates were similar to the controls, suggesting an interesting reparative and regenerative potential of irradiation-damaged/-dysfunctional salivary glands. The Figure below exemplifies some of these findings. Conclusions: Biocompatible, reproducible, and customizable self-assembling layer-by-layer core-shell delivery system is formulated and presented. Our findings suggest that localized sequential bioactive delivery of dual cytokines (in specific dose and order) can prevent irradiation-induced damage via reducing apoptosis and also has the potential to promote in situ proliferation of salivary gland cells; maxSALIVA is scalable (Good Manufacturing Practice or GMP production for human clinical trials) and patent-pending.

Keywords: saliva, head and neck cancer, nanotechnology, controlled drug delivery, xerostomia, mucositis, biopolymers, innovation

Procedia PDF Downloads 62