Search results for: tumor evolution

Authors: Mary Carmen Peloche Barrera

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Since its early years as an independent nation, the United States has been one of the main promoters regarding the recognition, legislation, and protection of human rights. In the matter of freedom, the founding father Thomas Jefferson envisioned the role of the U.S. as a defender of freedom and equality throughout the world. This founding ideal shaped America’s domestic and foreign policy in the 19th and the 20th century and became an aspiration of the ideals of the country to expand its values and institutions. The history of the emergence of human rights cannot be studied without making reference to leaders such as Woodrow Wilson, Franklin, and Eleanor Roosevelt, as well as Martin Luther King. Throughout its history, this country has proclaimed that the protection of the freedoms of men, both inside and outside its borders, is practically the reason for its existence. Although the United States was one of the first countries to recognize the existence of inalienable rights for individuals, as well as the main promoter of the Universal Declaration of Human Rights of 1948, the country has gone through critical moments that had led to questioning its commitment to the issue. Racial segregation, international military interventions, national security strategy, as well as national legislation on immigration, are some of the most controversial issues related to decisions and actions driven by the United States, which at the same time mismatched with its role as an advocate of human rights, both in the Americas and in the rest of the world. The aim of this paper is to study the swinging of the efforts and commitments of the United States towards human rights. The paper will analyze the history and evolution of human rights in the United States, to study the greatest challenges for the country in this matter. The paper will focus on both the domestic policy (related to demographic issues) and foreign policy (about its role in a post-war world). Currently, more countries are joining the multilateral efforts for the promotion and protection of human rights. At the same time, the United States is one of the least committed countries in this respect, having ratified only 5 of the 18 treaties emanating from the United Nations. The last ratification was carried out in 2002 and, since then, the country has been losing ground, in an increasingly vertiginous way, in its credibility and, even worse, in its role as leader of 'the free world'. With or without the United States, the protection of human rights should remain the main goal of the international community.

Keywords: United States, human rights, foreign policy, domestic policy

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Authors: Nihar Bheda

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Protecting digital assets such as networks, systems, and data from advanced cyber threats is the aim of Digital Immunity Systems (DIS), which are a subset of cybersecurity. With features like continuous monitoring, coordinated reactions, and long-term adaptation, DIS seeks to mimic biological immunity. This minimizes downtime by automatically identifying and eliminating threats. Traditional security measures, such as firewalls and antivirus software, are insufficient for enterprises, such as healthcare providers, given the rapid evolution of cyber threats. The number of medical record breaches that have occurred in recent years is proof that attackers are finding healthcare data to be an increasingly valuable target. However, obstacles to enhancing security include outdated systems, financial limitations, and a lack of knowledge. DIS is an advancement in cyber defenses designed specifically for healthcare settings. Protection akin to an "immune system" is produced by core capabilities such as anomaly detection, access controls, and policy enforcement. Coordination of responses across IT infrastructure to contain attacks is made possible by automation and orchestration. Massive amounts of data are analyzed by AI and machine learning to find new threats. After an incident, self-healing enables services to resume quickly. The implementation of DIS is consistent with the healthcare industry's urgent requirement for resilient data security in light of evolving risks and strict guidelines. With resilient systems, it can help organizations lower business risk, minimize the effects of breaches, and preserve patient care continuity. DIS will be essential for protecting a variety of environments, including cloud computing and the Internet of medical devices, as healthcare providers quickly adopt new technologies. DIS lowers traditional security overhead for IT departments and offers automated protection, even though it requires an initial investment. In the near future, DIS may prove to be essential for small clinics, blood banks, imaging centers, large hospitals, and other healthcare organizations. Cyber resilience can become attainable for the whole healthcare ecosystem with customized DIS implementations.

Keywords: digital immunity system, cybersecurity, healthcare data, emerging technology

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Authors: Xiaoya Yi, Yi He, Zhao Lu, Yang Zhang

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In the process of rapid urbanization, many historical cities have undergone excessive demolition and construction under the protection and renewal mechanism. The original pattern of the city has been changed, the urban context has been cut off, and historical features have gradually been lost. The historical city gradually changed into the form of decentralization and fragmentation. The understanding of the ancient city includes two levels. The first one refers to the ancient city on the physical space, which defined an ancient city by its historic walls. The second refers to the public perception of the image, which is derived from people's spatial identification of the ancient city. In ancient China, people draw maps to show their way of understanding the city. Starting from ancient maps and exploring the spatial characteristics of traditional Chinese cities from the perspective of urban imagery is a key clue to understanding the spatial characteristics of historical cities on an overall level. The spatial characteristics of the urban image presented by the ancient map are summarized into two levels by typology. The first is the spatial pattern composed of the center, axis and boundary. The second is the space element that contains the city, street, and sign system. Taking the ancient city of Shipu as a typical case, the "city image" in the ancient map is analyzed as a prototype, and it is projected into the current urban space. The research found that after a long period of evolution, the historical spatial pattern of the ancient city has changed from “dominant” to “recessive control”, and the historical spatial elements are non-centralized and fragmented. The wall that serves as the boundary of the ancient city is transformed into “fragmentary remains”, the streets and lanes that serve as the axis of the ancient city are transformed into “structural remains”, and the symbols of the ancient city center are transformed into “site remains”. Based on this, the paper proposed the methods of controlling the protection of land boundaries, the protecting of the streets and lanes, and the selective restoring of the city wall system and the sign system by accurate assessment. In addition, this paper emphasizes the continuity of the ancient city's traditional spatial pattern and attempts to explore a holistic conservation method of the ancient city in the modern context.

Keywords: ancient city protection, ancient maps, Shipu ancient city, urban intention

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Authors: Nabeel Mohammed Ali

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Background and significance of the study: This study focuses on the experiences, perspectives, and issues of the working-class Aboriginals and immigrants in Australia. In addition to dealing with their lives, struggles, and aspirations of working-class people, poetry of labor presents an insight into a neglected literary writing that goes beyond the social discourse of class distinction. In this contemporary context, it explores a broader spectrum of challenges and experiences, such as the complexities of modern labor, immigration, indigenous rights, social justice, multiculturalism, economic inequality, advocating for workers' rights and labor movements, the impact of globalization on local industries, and the evolution of labor in the digital age. Aims of the Study: The study will try to answer the following questions: What insights does poetics of labor provide to affect the literary creation of poetry at the time, as well as whether it can create a change in the social fabric of Australian diversity? What are the main themes and issues that Aboriginal and immigrant poets address in their works? How do they reflect the realities and challenges of working-class people in Australia? How do they use language, form, and style to convey their messages and emotions? How do the poets engage with and critique the dominant narratives and ideologies of Australian society and culture? How do they challenge or resist the stereotypes, prejudices, and discrimination that they face? And how do they show solidarity or empathy with others who share similar struggles or aspirations? Methodology: The study will utilize traditional Marxist paradigms to analyze the poetry of the selected poets in the context of the evolving sociopolitical landscape of the 21st century. The Neo-Marxist literary criticism is used as a theoretical tool to analyze the texts. The concept of Power dynamics to analyze the intersectionality of race, labor and class. Findings: The poetry of contemporary Australian Aboriginal and immigrant poets labor, represents a critical, yet under-explored, discussion of the intersection of labor, class, and a multicultural identity. The study will deal with the poetry of the Aboriginal poet Ali Cobby Eckermann (1963- ) and the immigrant Chinese poet Ouyang Yu ( 1955- ).

Keywords: aboriginals, immigrants, Australia, working-class, Ali eckermann, ouyang Yu

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Authors: M. Cardenas-Garcia, P. P. Gonzalez-Perez

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Intercellular communication is a necessary condition for cellular functions and it allows a group of cells to survive as a population. Throughout this interaction, the cells work in a coordinated and collaborative way which facilitates their survival. In the case of cancerous cells, these take advantage of intercellular communication to preserve their malignancy, since through these physical unions they can send signs of malignancy. The Wnt/β-catenin signaling pathway plays an important role in the formation of intercellular communications, being also involved in a large number of cellular processes such as proliferation, differentiation, adhesion, cell survival, and cell death. The modeling and simulation of cellular signaling systems have found valuable support in a wide range of modeling approaches, which cover a wide spectrum ranging from mathematical models; e.g., ordinary differential equations, statistical methods, and numerical methods– to computational models; e.g., process algebra for modeling behavior and variation in molecular systems. Based on these models, different simulation tools have been developed from mathematical ones to computational ones. Regarding cellular and molecular processes in cancer, its study has also found a valuable support in different simulation tools that, covering a spectrum as mentioned above, have allowed the in silico experimentation of this phenomenon at the cellular and molecular level. In this work, we simulate and explore the complex interaction patterns of intercellular communication in cancer cells using the Cellulat bioinformatics tool, a computational simulation tool developed by us and motivated by two key elements: 1) a biochemically inspired model of self-organizing coordination in tuple spaces, and 2) the Gillespie’s algorithm, a stochastic simulation algorithm typically used to mimic systems of chemical/biochemical reactions in an efficient and accurate way. The main idea behind the Cellulat simulation tool is to provide an in silico experimentation environment that complements and guides in vitro experimentation in intra and intercellular signaling networks. Unlike most of the cell signaling simulation tools, such as E-Cell, BetaWB and Cell Illustrator which provides abstractions to model only intracellular behavior, Cellulat is appropriate for modeling both intracellular signaling and intercellular communication, providing the abstractions required to model –and as a result, simulate– the interaction mechanisms that involve two or more cells, that is essential in the scenario discussed in this work. During the development of this work we made evident the application of our computational simulation tool (Cellulat) for the modeling and simulation of intercellular communication between normal and cancerous cells, and in this way, propose key molecules that may prevent the arrival of malignant signals to the cells that surround the tumor cells. In this manner, we could identify the significant role that has the Wnt/β-catenin signaling pathway in cellular communication, and therefore, in the dissemination of cancer cells. We verified, using in silico experiments, how the inhibition of this signaling pathway prevents that the cells that surround a cancerous cell are transformed.

Keywords: cancer cells, in silico approach, intercellular communication, key molecules, modeling and simulation

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Authors: Kym Drady

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This paper considers whether creativity is the missing link which would allow the evolution of organisational behaviour and profitability if it was ‘released’. It suggests that although many organisations try to engage their workforce and expect innovation they fail to provide the means for its achievement. The paper suggests that creative thinking is the ‘glue’ which links organisational performance to profitability. A key role of a university today, is to produce skilled and capable graduates. Increasing competition and internationalisation has meant that the employability agenda has never been more prominent within the field of education. As such it should be a key consideration when designing and developing a curriculum. It has been suggested that creativity is a valuable personal skill and perhaps should be the focus of an organisations business strategy in order for them to increase their competitive advantage in the twenty first century. Flexible and agile graduates are now required to become creative in their use of skills and resources in an increasingly complex and sophisticated global market. The paper, therefore, questions that if this is the case why then does creativity fail to appear as a key curriculum subject in many business schools. It also considers why policy makers continue to neglect this critical issue when it could offer the ‘key’ to economic prosperity. Recent literature does go some way to addressing by suggesting that small clusters of UK Universities have started including some creativity in their PDP work. However, this paper builds on this work and proposes that that creativity should become a central component of the curriculum. The paper suggests that creativity should appear in every area of the curriculum and that it should act as the link that connects productivity to profitability rather than being marginalised as an additional part of the curriculum. A range of data gathering methods have been used but each has been drawn from a qualitative base as it was felt that due to nature of the study individual’s thoughts and feelings needed to be examined and reflection was important. The author also recognises the importance of her own reflection both on the experiences of the students and their later working experiences as well as on the creative elements within the programme that she delivered. This paper has been drawn from research undertaken by the author in relation to her PhD study which explores the potential benefits of including creativity in the curriculum within business schools and the added value this could make to their employability. To conclude, creativity is, in the opinion of the author, the missing link to organisational profitability and as such should be prioritised especially by higher education providers.

Keywords: business curriculum, business curriculum, higher education, creative thinking and problem-solving, creativity

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Authors: Zameerpal Kaur

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Ecocriticism comes into existence in 1990s, it tries to explore the relationship of literature with the natural world and further it examines the role that natural surroundings and environment play in the minds of the creative writers during their imagination and creative process. The present study is an attempt to focus on the comparative ecocritical analysis of Shiv Kumar Batalvi and Surjit Patar’s selected poetry in the theoretical framework of ecocriticism in order to shed light on the poet’s vigilant views about the relationship of human life and nature. Shiv Kumar Batalvi is a renowned modern Punjabi poet. He is essentially a poet of nature and love. His opinions towards nature support his position to be considered as a major representative of recent environmental issues and ecocritical concerns in Punjabi literature. He is one of the most outstanding modern Punjabi poets, is endowed with the most artistic temperament in whose poetry nature always has a dominating existence. He seems to consciously portray the scenes of natural surroundings into his poetry; in fact the titles of his poems in themselves signify his love for the nature. Surjit Patar, an imminent modern Punjabi poet tries to present a different picture of nature into his poems; he also uses to write poems about contemporary problems. Surjit Patar’s radical quarrel with the modern cultural context makes him reject all the absolutes and finalities in the form of transcendental reason and religion, history and evolution, he freely writes about the deterioration of nature at selfish materialistic society. He is modern poet who weaves the natural imagery with the syntax of his poems. Patar’s work reflects a universal voice that is dribbled with nuanced humanism and a sense of modernity that seemed neither dated, nor trapped in regional boundaries. Through his poetry he has given a voice to the fragile, disrupting borders, disturbing the status quo. An attempt to analyse the poetic works of above said poets from ecocritical perspective as well as especially focussing on various aspects of ecocriticism like ecocentric ethics, ecoaesthetics, anthropomorphism etc. has been made throughout the comparative study of the selected works.

Keywords: anthropocentrism, degradation, environment and literature, nature

Procedia PDF Downloads 445

Authors: Enrico Gugliandolo, Salvatore Cuzzocrea, Rosalia Crupi

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Osteoarthritis (OA) is one of the most common chronic pain conditions in dogs and cats. OA pain is currently viewed as a mixed phenomenon involving both inflammatory and neuropathic mechanisms at the peripheral (joint) and central (spinal and supraspinal) levels. Oxidative stress has been implicated in OA pain. Although nonsteroidal anti-inflammatory drugs are commonly prescribed for OA pain, they should be used with caution in pets because of adverse effects in the long term and controversial efficacy on neuropathic pain. An unmet need remains for safe and effective long-term treatments for OA pain. Palmitoyl-glucosamine (PGA) is an analogue of the ALIAamide palmitoylethanolamide, i.e., a body’s own endocannabinoid-like compound playing a sentinel role in nociception. PGA, especially in the micronized formulation, was shown safe and effective in OA pain. The aim of this study was to investigate the effect of a co-micronized formulation of PGA with the natural antioxidant curcumin (PGA-cur) on OA pain. Ten Sprague-Dawley male rats were used for each treatment group. The University of Messina Review Board for the care and use of animals authorized the study. On day 0, rats were anesthetized (5.0% isoflurane in 100% O2) and received intra-articular injection of MIA (3 mg in 25 μl saline) in the right knee joint, with the left being injected an equal volume of saline. Starting the third day after MIA injection, treatments were administered orally three times per week for 21 days, at the following doses: PGA 20 mg/kg, curcumin 10 mg/kg, PGA-cur (2:1 ratio) 30 mg/kg. On day 0 and 3, 7, 14 and 21 days post-injection, mechanical allodynia was measured using a dynamic plantar Von Frey hair aesthesiometer and expressed as paw withdrawal threshold (PWT) and latency (PWL). Motor functional recovery of the rear limb was evaluated on the same time points by walking track analysis using the sciatic functional index. On day 21 post-MIA injection, the concentration of the following inflammatory and nociceptive mediators was measured in serum using commercial ELISA kits: tumor necrosis factor alpha (TNF-α), interleukin-1 beta (IL-1β), nerve growth factor (NGF) and matrix metalloproteinase-1-3-9 (MMP-1, MMP-3, MMP-9). The results were analyzed by ANOVA followed by Bonferroni post-hoc test for multiple comparisons. Micronized PGA reduced neuropathic pain, as shown by the significant higher PWT and PWL values compared to vehicle group (p < 0.0001 for all the evaluated time points). The effect of PGA-cur was superior at all time points (p < 0.005). PGA-cur restored motor function already on day 14 (p < 0.005), while micronized PGA was effective a week later (D21). MIA-induced increase in the serum levels of all the investigated mediators was inhibited by PGA-cur (p < 0.01). PGA was also effective, except on IL-1 and MMP-3. Curcumin alone was inactive in all the experiments at any time point. The encouraging results suggest that PGA-cur may represent a valuable option in OA pain management and warrant further confirmation in well-powered clinical trials.

Keywords: ALIAmides, curcumin, osteoarthritis, palmitoyl-glucosamine

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Authors: Janet Modu, Jean-Francois Georgin, Laurent Briancon, Eric Antoinet

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The current practice during the repowering phase of wind turbines is deconstruction of existing foundations and construction of new foundations to accept larger wind loads or once the foundations have reached the end of their service lives. The ongoing research project FUI25 FEDRE (Fondations d’Eoliennes Durables et REpowering) therefore serves to propose scalable wind turbine foundation designs to allow reuse of the existing foundations. To undertake this research, numerical models and laboratory-scale models are currently being utilized and implemented in the GEOMAS laboratory at INSA Lyon following instrumentation of a reference wind turbine situated in the Northern part of France. Sensors placed within both the foundation and the underlying soil monitor the evolution of stresses from the foundation’s early age to stresses during service. The results from the instrumentation form the basis of validation for both the laboratory and numerical works conducted throughout the project duration. The study currently focuses on the effect of coupled mechanisms (Thermal-Hydro-Mechanical-Chemical) that induce stress during the early age of the reinforced concrete foundation, and scale factor considerations in the replication of the reference wind turbine foundation at laboratory-scale. Using THMC 3D models on COMSOL Multi-physics software, the numerical analysis performed on both the laboratory-scale and the full-scale foundations simulate the thermal deformation, hydration, shrinkage (desiccation and autogenous) and creep so as to predict the initial damage caused by internal processes during concrete setting and hardening. Results show a prominent effect of early age properties on the damage potential in full-scale wind turbine foundations. However, a prediction of the damage potential at laboratory scale shows significant differences in early age stresses in comparison to the full-scale model depending on the spatial position in the foundation. In addition to the well-known size effect phenomenon, these differences may contribute to inaccuracies encountered when predicting ultimate deformations of the on-site foundation using laboratory scale models.

Keywords: cement hydration, early age behavior, reinforced concrete, shrinkage, THMC 3D models, wind turbines

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Authors: Princess Ncube

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In the context of South Africa's banking sector, the prevention of bank failures is of paramount importance to ensure financial stability and economic growth. This paper focuses on the role of regulatory frameworks in safeguarding the resilience of South African banks and mitigating the risks of failures. It aims to assess the effectiveness of existing regulatory measures and proposes strategies to enhance the resilience of financial institutions in the country. The paper begins by examining the specific regulatory frameworks in place in South Africa, including capital adequacy requirements, stress testing methodologies, risk management guidelines, and supervisory practices. It delves into the evolution of these measures in response to lessons learned from past financial crises and their relevance in the unique South African banking landscape. Drawing on empirical evidence and case studies specific to South Africa, this paper evaluates the effectiveness of regulatory frameworks in preventing bank failures within the country. It analyses the impact of these frameworks on crucial aspects such as early detection of distress signals, improvements in risk management practices, and advancements in corporate governance within South African financial institutions. Additionally, it explores the interplay between regulatory frameworks and the specific economic environment of South Africa, including the role of macroprudential policies in preventing systemic risks. Based on the assessment, this paper proposes recommendations to strengthen regulatory frameworks and enhance their effectiveness in bank failure prevention in South Africa. It explores avenues for refining existing regulations to align capital requirements with the risk profiles of South African banks, enhancing stress testing methodologies to capture specific vulnerabilities, and fostering better coordination among regulatory authorities within the country. Furthermore, it examines the potential benefits of adopting innovative approaches, such as leveraging technology and data analytics, to improve risk assessment and supervision in the South African banking sector.

Keywords: banks, resolution, liquidity, regulation

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Authors: A. Hakem, Y. Bouafia

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Characterization of materials used for various mechanical components is of great importance in their design. Several studies were conducted by various authors in order to improve their physical and/or chemical properties in general and mechanical or metallurgical properties in particular. The foundry alloy AlSi7Zn3Cu2Mg is one of the main components constituting the various mechanisms for the implementation of applications and various industrial projects. Obtaining a reliable product is not an easy task; several results proposed by different authors show sometimes results that can contradictory. Due to their high mechanical characteristics, these alloys are widely used in engineering. Silicon improves casting properties and magnesium allows heat treatment. It is thus possible to obtain various degrees of hardening and therefore interesting compromise between tensile strength and yield strength, on one hand, and elongation, on the other hand. These mechanical characteristics can be further enhanced by a series of mechanical treatments or heat treatments. Their light weight coupled with high mechanical characteristics, aluminum alloys are very much used in cars and aircraft industry. The present study is focused on the influence of heat treatments which cause significant micro structural changes, usually hardening by variation of annealing temperatures by increments of 10°C and 20°C on the evolution of the main elastic characteristics, the resistance, the ductility and the structural characteristics of AlSi7Zn3Cu2Mg foundry alloy cast in sand by gravity. These elastic properties are determined in three directions for each specimen of dimensions 200x150x20 mm³ by the ultrasonic method based on acoustic or elastic waves. The hardness, the micro hardness and the structural characteristics are evaluated by a non-destructive method. The aim of this work is to study the hardening ability of AlSi7Zn3Cu2Mg alloy by considering ten states. To improve the mechanical properties obtained with the raw casting, one should use heat treatment for structural hardening; the addition of magnesium is necessary to increase the sensitivity to this specific heat treatment: Treatment followed by homogenization which generates a diffusion of atoms in a substitution solid solution inside a hardening furnace at 500°C during 8h, followed immediately by quenching in water at room temperature 20 to 25°C, then an ageing process for 17h at room temperature and at different annealing temperature (150, 160, 170, 180, 190, 240, 200, 220 and 240°C) for 20h in an annealing oven. The specimens were allowed to cool inside the oven.

Keywords: aluminum, foundry alloy, magnesium, mechanical characteristics, silicon

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Authors: Spase Janevski

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We, as designers, should be aware of the consequences of our material selection, at the early stages of the design process. Some of the designer’s decisions can have a very significant impact on design for sustainability. The influence of this concept has led to years of research studies into eco-friendly materials and their potentials for creating new sustainable products. In order to answer the question, 'how cork has become a design trend', this paper will present an overview of the implications of the concept of design for sustainability on the potential uses of cork material. A decade ago, cork as a material had an association with wine stoppers, but with the evolution of sustainable product design as part of the concept of design for sustainability, cork now offers product designers a wide range of new materials and applications. The purpose of this paper is to show how the phenomenon of sustainability has had an impact on the progress of the material which is currently not being an integral component of the design material palette. At the beginning, the nature of the relationship between cork and sustainability will be explained through the following stages: 1) fundamental understanding of the concept of Design for Sustainability and the importance of material selection for sustainable product design, and 2) the importance of cork oak trees for the environment and the environmental impacts of cork products. In order to examine and present the influence of the sustainability on the innovation in cork applications, the paper will provide a historical overview of designing with cork. The overview will consist of four stages: 1) pre-industrial period - the period when ancient nations used cork and amphoras to store their wine; 2) industrial period - emergence and industrialization of well-known wine stoppers; 3) post-industrial period - commercializing cork products in the area of floors and coverings and first developments in industrial research; and 4) the period when large cork realized the importance of sustainability and started to focus more markedly on research and development. The existence of new cork materials, the investigation in new applications and the investment in new innovations have proved that the sustainability approach has had a great influence on the revival of this material. In addition, the paper will present some of the new cork innovative materials and applications and their potentials for designing promising and sustainable solutions with additive manufacturing technologies, such as 3D printing. Lastly, the paper will introduce some questions for further study, such as the environmental impacts of the new hybrid materials and the gap between cork industry and cork research and development teams. The paper concludes by stating that cork is not only a material for wine stoppers anymore, thanks to the awareness of the concept of design for sustainability.

Keywords: cork, design for sustainability, innovation, sustainable materials

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Authors: Sean Yao Zu Kong, Khong Yik Chew

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Introduction: We described a case report of the successful use of advanced surgical techniques in a patient with recurrent breast cancer who underwent a wide resection including the hemi-sternum, clavicle, multiple ribs, and a lobe of the lung due to tumor involvement. This extensive resection exposed critical structures, requiring a creative approach to reconstruction. To address this complex chest wall reconstruction, a free fibula flap and a 4-zone rectus abdominis musculocutaneous flap were successfully utilized. The use of a free vascularized bone flap allowed for rapid osteointegration and resistance against osteoradionecrosis after adjuvant radiation, while a four-zone tram flap allowed for reconstruction of both the chest wall and breast mound. Although limited recipient vessels made free flaps challenging, the free fibula flap served as both a bony reconstruction and vascular conduit, supercharged with the distal peroneal artery and veins of the peroneal artery from the fibula graft. Our approach highlights the potential of advanced surgical techniques to improve outcomes in complex cases of chest wall reconstruction in patients with recurrent breast cancer, which is becoming increasingly relevant as breast cancer incidence rates increases. Case presentation: This report describes a successful reconstruction of a patient with recurrent breast cancer who required extensive resection, including the anterior chest wall, clavicle, and sternoclavicular joint. Challenges arose due to the loss of accessory muscles and the non-rigid rib cage, which could lead to compromised ventilation and instability. A free fibula osteocutaneous flap and a four-zone TRAM flap with vascular supercharging were utilized to achieve long-term stability and function. The patient has since fully recovered, and during the review, both flaps remained viable, and chest mound reconstruction was satisfactory. A planned nipple/areolar reconstruction was offered pending the patient’s decision after adjuvant radiotherapy. Conclusion: In conclusion, this case report highlights the successful use of innovative surgical techniques in addressing a complex case of recurrent breast cancer requiring extensive resection and radical reconstruction. Our approach, utilized a combination of a free fibula flap and a 4-zone rectus abdominis musculocutaneous flap, demonstrates the potential for advanced techniques in chest wall reconstruction to minimize complications and ensure long-term stability and function. As the incidence of breast cancer continues to rise, it is crucial that healthcare professionals explore and utilize innovative techniques to improve patient outcomes and quality of life.

Keywords: free fibula flap, rectus abdominis musculocutaneous flap, post-adjuvant radiotherapy, reconstructive surgery, malignancy

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Authors: Matteo Nicoli, Gianvito Colucci, Valeria Di Cosmo, Daniele Lerede, Laura Savoldi

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The transport sector is currently responsible for approximately 1/3 of greenhouse gas emissions in Europe. In the wider context of achieving carbon neutrality of the global energy system, different alternatives are available to decarbonizethe transport sector. In particular, while electricity is already the most consumed energy commodity in rail transport, battery electric vehicles are one of the zero-emissions options on the market for road transportation. On the other hand, hydrogen-based fuel cell vehicles are available for road and non-road vehicles. The European Commission is strongly pushing toward the integration of hydrogen in the energy systems of European countries and its widespread adoption as an energy vector to achieve the Green Deal targets. Furthermore, the Italian government is defining hydrogen-related objectives with the publication of a dedicated Hydrogen Strategy. The adoption of energy system optimization models to study the possible penetration of alternative zero-emitting transport technologies gives the opportunity to perform an overall analysis of the effects that the development of innovative technologies has on the entire energy system and on the supply-side, devoted to the production of energy carriers such as hydrogen and electricity. Using an open-source modeling framework such as TEMOA, this work aims to compare the role of hydrogen and electric vehicles in the decarbonization of the transport sector. The analysis investigates the advantages and disadvantages of adopting the two options, from the economic point of view (costs associated with the two options) and the environmental one (looking at the emissions reduction perspectives). Moreover, an analysis on the profitability of the investments in hydrogen and electric vehicles will be performed. The study investigates the evolution of energy consumption and greenhouse gas emissions in different transportation modes (road, rail, navigation, and aviation) by detailed analysis of the full range of vehicles included in the techno-economic database used in the TEMOA model instance adopted for this work. The transparency of the analysis is guaranteed by the accessibility of the TEMOA models, based on an open-access source code and databases.

Keywords: battery electric vehicles, decarbonization, energy system optimization models, fuel cell vehicles, hydrogen, open-source modeling, TEMOA, transport

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Authors: Brennan Lodge

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Amidst a complex regulatory landscape, Retrieval Augmented Generation (RAG) emerges as a transformative tool for Governance Risk and Compliance (GRC) officers. This paper details the application of RAG in synthesizing Large Language Models (LLMs) with external knowledge bases, offering GRC professionals an advanced means to adapt to rapid changes in compliance requirements. While the development for standalone LLM’s (Large Language Models) is exciting, such models do have their downsides. LLM’s cannot easily expand or revise their memory, and they can’t straightforwardly provide insight into their predictions, and may produce “hallucinations.” Leveraging a pre-trained seq2seq transformer and a dense vector index of domain-specific data, this approach integrates real-time data retrieval into the generative process, enabling gap analysis and the dynamic generation of compliance and risk management content. We delve into the mechanics of RAG, focusing on its dual structure that pairs parametric knowledge contained within the transformer model with non-parametric data extracted from an updatable corpus. This hybrid model enhances decision-making through context-rich insights, drawing from the most current and relevant information, thereby enabling GRC officers to maintain a proactive compliance stance. Our methodology aligns with the latest advances in neural network fine-tuning, providing a granular, token-level application of retrieved information to inform and generate compliance narratives. By employing RAG, we exhibit a scalable solution that can adapt to novel regulatory challenges and cybersecurity threats, offering GRC officers a robust, predictive tool that augments their expertise. The granular application of RAG’s dual structure not only improves compliance and risk management protocols but also informs the development of compliance narratives with pinpoint accuracy. It underscores AI’s emerging role in strategic risk mitigation and proactive policy formation, positioning GRC officers to anticipate and navigate the complexities of regulatory evolution confidently.

Keywords: cybersecurity, gen AI, retrieval augmented generation, cybersecurity defense strategies

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Authors: Anastasia V. Kovaleva, Alena A. Ryabova, Vladimir N. Kasatkin

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Background: The most simple form of entrainment to a sensory (typically auditory) rhythmic stimulus involves perceiving and synchronizing movements with an isochronous beat with one level of periodicity, such as that produced by a metronome. Children with pediatric cancer usually treated with chemo- and radiotherapy. Because of such treatment, psychologists and health professionals declare cognitive and motor abilities decline in cancer patients. The purpose of our study was to measure working memory characteristics with association with audio-motor synchronization tasks, also involved some memory resources, in children with different degrees of central nervous system lesions: posterior fossa tumors, acute lymphoblastic leukemia, and healthy controls. Methods: Our sample consisted of three groups of children: children treated for posterior fossa tumors (PFT-group, n=42, mean age 12.23), children treated for acute lymphoblastic leukemia (ALL-group, n=11, mean age 11.57) and neurologically healthy children (control group, n=36, mean age 11.67). Participants were tested for working memory characteristics with Cambridge Neuropsychological Test Automated Battery (CANTAB). Pattern recognition memory (PRM) and spatial working memory (SWM) tests were applied. Outcome measures of PRM test include the number and percentage of correct trials and latency (speed of participant’s response), and measures of SWM include errors, strategy, and latency. In the synchronization tests, the instruction was to tap out a regular beat (40, 60, 90 and 120 beats per minute) in synchrony with the rhythmic sequences that were played. This meant that for the sequences with an isochronous beat, participants were required to tap into every auditory event. Variations of inter-tap-intervals and deviations of children’s taps from the metronome were assessed. Results: Analysis of variance revealed the significant effect of group (ALL, PFT and control) on such parameters as short-term PRM, SWM strategy and errors. Healthy controls demonstrated more correctly retained elements, better working memory strategy, compared to cancer patients. Interestingly that ALL patients chose the bad strategy, but committed significantly less errors in SWM test then PFT and controls did. As to rhythmic ability, significant associations of working memory were found out only with 40 bpm rhythm: the less variable were inter-tap-intervals of the child, the more elements in memory he/she could retain. The ability to audio-motor synchronization may be related to working memory processes mediated by the prefrontal cortex whereby each sensory event is actively retrieved and monitored during rhythmic sequencing. Conclusion: Our results suggest that working memory, tested with appropriate cognitive methods, is associated with the ability to synchronize movements with rhythmic sounds, especially in sub-second intervals (40 per minute).

Keywords: acute lymphoblastic leukemia (ALL), audio-motor synchronization, posterior fossa tumor, working memory

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Authors: Zhou Congling

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The integration of private tutoring has emerged as an indispensable facet in the acquisition of language proficiency beyond formal educational settings. Notably, there has been a discernible surge in the demand for private English tutoring, specifically geared towards the preparation for internationally recognized gatekeeping examinations, such as IELTS, TOEFL, GMAT, and GRE. This trajectory has engendered an escalating need for English Language Teaching Assistants (ELTAs) operating within the realm of Private Tutoring Schools (PTSs). The objective of this study is to unravel the intricate process by which these ELTAs formulate their professional identities in the nascent stages of their careers as English educators, as well as to delineate their perceptions regarding their professional trajectories. The construct of language teacher identity is inherently multifaceted, shaped by an amalgamation of individual, societal, and cultural determinants, exerting a profound influence on how language educators navigate their professional responsibilities. This investigation seeks to scrutinize the experiential and influential factors that mold the identities of ELTAs in PTSs, particularly post the culmination of their language-oriented academic programs. Employing a qualitative narrative inquiry approach, this study aims to delve into the nuanced understanding of how ELTAs conceptualize their professional identities and envision their future roles. The research methodology involves purposeful sampling and the conduct of in-depth, semi-structured interviews with ten participants. Data analysis will be conducted utilizing Barkhuizen’s Short Story Analysis, a method designed to explore a three-dimensional narrative space, elucidating the intricate interplay of personal experiences and societal contexts in shaping the identities of ELTAs. The anticipated outcomes of this study are poised to contribute substantively to a holistic comprehension of ELTA identity formation, holding practical implications for diverse stakeholders within the private tutoring sector. This research endeavors to furnish insights into strategies for the retention of ELTAs and the enhancement of overall service quality within PTSs.

Keywords: China, English language teacher, narrative inquiry, private tutoring school, teacher identity

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Authors: Ke Wang, Zhu Wang

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Coordinating and promoting urban and rural development has been a new round of institutional change in Zhejiang province since 2004. And this plan was fully implemented, which showed that the isolation between the urban and rural areas had gradually diminished. Little by little, an infiltration interface that is dynamic, flexible and interactive is formed, and this morphological structure starts to appear on the landscape form in the surrounding villages. In order to study the specific function and formation of the structure in the context of industrial revolution, Bimen village located on the interface between Anji Township, Huzhou and Yuhang District, Hangzhou is taken as the case. Anji township is in the cross area between Yangtze River delta economic circle and innovation center in Hangzhou. Awarded with ‘Chinese beautiful village’, Bimen has witnessed the growing process of infiltration in ecology, economy, technology and culture on the interface. Within the opportunity, Bimen village presents internal reformation to adapt to the energy exchange with urban areas. In the research, the reformation is to adjust the industrial structure, to upgrade the local special bamboo crafts, to release space for activities, and to establish infrastructures on the interface. The characteristic of an interface is elasticity achieved by introducing an Internet platform using ‘O2O’ agriculture method to connect cities and farmlands. There is a platform of this kind in Bimen named ‘Xiao Mei’. ‘Xiao’ in Chinese means small, ‘Mei’ means beautiful, which indicates the method to refine the landscape form. It turns out that the new agriculture mode will strengthen the interface by orienting the Third Party Platform upon the old dynamic basis and will bring new vitality for economy development in Bimen village. The research concludes opportunities and challenges generated by the evolution of the infiltration interface. It also proposes strategies for how to organically adapt to the urbanization process. Finally it demonstrates what will happen by increasing flexibility in the landscape forms of suburbs in the Bimen village.

Keywords: Bimen village, infiltration interface, flexibility, suburban landscape form

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Authors: Janice Haworth, Karamoko Camara, Marie-Therèse Dramou, Kokoly Haba, Daniel Léno, Augustin Mara, Adama Noël Oulari, Silafa Tolno, Noël Zoumanigui

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The traditional rhythms of the West African country of Guinea have played a centuries-long role in defining the different people groups that make up the country. Throughout their history, before and since colonization by the French, the different ethnicities have used their traditional music as a distinct part of their historical identities. That is starting to change. Guinea is an impoverished nation created in the early twentieth-century with little regard for the history and cultures of the people who were included. The traditional rhythms of the different people groups and their heritages have remained. Fifteen individual traditional Guinean rhythms were chosen to represent popular rhythms from the four geographical regions of Guinea. Each rhythm was traced back to its native village and video recorded on-site by as many different local performing groups as could be located. The cyclical patterns rhythms were transcribed via a circular, spatial design and then copied into a box notation system where sounds happening at the same time could be studied. These rhythms were analyzed for their consistency-over-performance in a Fundamental Rhythm Pattern analysis so rhythms could be compared for how they are changing through different performances. The analysis showed that the traditional rhythm performances of the Middle and Forest Guinea regions were the most cohesive and showed the least evidence of change between performances. The role of music in each of these regions is both limited and focused. The Coastal and High Guinea regions have much in common historically through their ethnic history and modern-day trade connections, but the rhythm performances seem to be less consistent and demonstrate more changes in how they are performed today. In each of these regions the role and usage of music is much freer and wide-spread. In spite of advances being made as a country, different ethnic groups still frequently only respond and participate (dance and sing) to the music of their native ethnicity. There is some evidence that this self-imposed musical barrier is beginning to change and evolve, partially through the development of better roads, more access to electricity and technology, the nation-wide Ebola health crisis, and a growing self-identification as a unified nation.

Keywords: cultural identity, Guinea, traditional rhythms, west Africa

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Authors: Peyton M. Provenzano

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This paper draws primarily upon the framework of necropolitics and presents California as itself a former frontier, colony, and late-modern settler society. The convergence of these successive and overlapping regimes of state terror is actualized and traceable through an analysis of historical and contemporary police practices. At the behest of the Spanish Crown and with the assistance of the Spanish military, the Catholic Church led the original expedition to colonize California. The indigenous populations of California were subjected to brutal practices of confinement and enslavement at the missions. After the annex of California by the United States, the western-most territory became an infamous frontier where new settlers established vigilante militias to enact violence against indigenous populations to protect their newly stolen land. Early mining settlements sought to legitimize and fund vigilante violence by wielding the authority of rudimentary democratic structures. White settlers circulated petitions for funding to establish a volunteer company under California’s Militia Law for ‘protection’ against the local indigenous populations. The expansive carceral practices of Los Angelinos at the turn of the 19th century exemplify the way in which California solidified its regime of exclusion as a white settler society. Drawing on recent scholarship that queers the notion of biopower and names police as street-level sovereigns, the police murder of Kayla Moore is understood as the latest manifestation of a carceral regime of exclusion and genocide. Kayla Moore was an African American transgender woman living with a mental health disability that was murdered by Berkeley police responding to a mental health crisis call in 2013. The intersectionality of Kayla’s identity made her hyper-vulnerable to state-sanctioned violence. Kayla was a victim not only of the explicitly racial biopower of police, nor the regulatory state power of necropolitics but of the ‘asphyxia’ that was intended to invisibilize both her life and her murder.

Keywords: asphyxia, biopower, california, carceral state, genocide, necropolitics, police, police violence

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Authors: Anupalli Roja Rani, Pavithra Dasari

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Background: Among several, breast cancer has emerged as the most common female cancer in developing countries. It is the most common cause of cancer-related deaths worldwide among women. It is a molecularly and clinically heterogeneous disease. Moreover, it is a hormone–dependent tumor in which estrogens can regulate the growth of breast cells by binding with estrogen receptors (ERs). Moreover, the use of natural products in cancer therapeutics is due to their properties of biocompatibility and less toxicity. Plants are the vast reservoirs for various bioactive compounds. Coleus barbatus (Lamiaceae) contains anticancer properties against several cancer cell lines. Method: In the present study, an attempt is being made to enrich the knowledge of the anticancer activity of pure compounds extracted from Coleus barbatus (Andrew). On human breast cancer cell lines MCF-7. Here in, we are assessing the antiproliferative activity of Coleus barbatus (Andrew) plant extracts against MCF 7 and also evaluating their toxicity in normal human mammary cell lines such as Human Mammary Epithelial Cells (HMEC). The active fraction of plant extract was further purified with the help of Flash chromatography, Medium Pressure Liquid Chromatography (MPLC) and preparative High-Performance Liquid Chromatography (HPLC). The structure of pure compounds will be elucidated by using modern spectroscopic methods like Nuclear magnetic resonance (NMR), Electrospray Ionisation Mass Spectrometry (ESI-MS) methods. Later, the growth inhibition morphological assessment of cancer cells and cell cycle analysis of purified compounds were assessed using FACS. The growth and progression of signaling molecules HER2, GRP78 was studied by secretion assay using ELISA and expression analysis by flow cytometry. Result: Cytotoxic effect against MCF-7 with IC50 values were derived from dose response curves, using six concentrations of twofold serially diluted samples, by SOFTMax Pro software (Molecular device) and respectively Ellipticine and 0.5% DMSO were used as a positive and negative control. Conclusion: The present study shows the significance of various bioactive compounds extracted from Coleus barbatus (Andrew) root material. It acts as an anti-proliferative and shows cytotoxic effects on human breast cancer cell lines MCF7. The plant extracts play an important role pharmacologically. The whole plant has been used in traditional medicine for decades and the studies done have authenticated the practice. Earlier, as described, the plant has been used in the ayurveda and homeopathy medicine. However, more clinical and pathological studies must be conducted to investigate the unexploited potential of the plant. These studies will be very useful for drug designing in the future.

Keywords: coleus barbatus, HPLC, MPLC, NMR, MCF7, flash chromatograph, ESI-MS, FACS, ELISA.

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Authors: Olumuyiwa Olusola Falowo

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One of the objectives of the Millennium Development Goals is to have sustainable access to safe drinking water and basic sanitation. In line with this objective, an assessment of groundwater quality was carried out in Odigbo Local Government Area of Ondo State in November – February, 2019 to assess the drinking, domestic and irrigation uses of the water. Samples from 30 randomly selected ground water sources; 16 shallow wells and 14 from boreholes and analyzed using American Public Health Association method for the examination of water and wastewater. Water quality index calculation, and diagrams such as Piper diagram, Gibbs diagram and Wilcox diagram have been used to assess the groundwater in conjunction with irrigation indices such as % sodium, sodium absorption ratio, permeability index, magnesium ratio, Kelly ratio, and electrical conductivity. In addition statistical Principal component analysis were used to determine the homogeneity and source(s) influencing the chemistry of the groundwater. The results show that all the parameters are within the permissible limit of World Health Organization. The physico-chemical analysis of groundwater samples indicates that the dominant major cations are in decreasing order of Na+, Ca2+, Mg2+, K+ and the dominant anions are HCO-3, Cl-, SO-24, NO-3. The values of water quality index varies suggest a Good water (WQI of 50-75) accounts for 70% of the study area. The dominant groundwater facies revealed in this study are the non-carbonate alkali (primary salinity) exceeds 50% (zone 7); and transition zone with no one cation-anion pair exceeds 50% (zone 9), while evaporation; rock–water interaction, and precipitation; and silicate weathering process are the dominant processes in the hydrogeochemical evolution of the groundwater. The study indicates that waters were found within the permissible limits of irrigation indices adopted, and plot on excellent category on Wilcox plot. In conclusion, the water in the study area are good/suitable for drinking, domestic and irrigation purposes with low equivalent salinity concentrate and moderate electrical conductivity.

Keywords: equivalent salinity concentration, groundwater quality, hydrochemical facies, principal component analysis, water-rock interaction

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Authors: Suman Podder

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As Australian ‘Open Banking’ allows customers to share their financial data with accredited Third-Party Providers (‘TPPs’), it is necessary to evaluate whether the regulators have achieved the balance between protecting customer data privacy and promoting data-related innovation. Recognising the need to increase customers’ influence on their own data, and the benefits of data-related innovation, the Australian Government introduced ‘Consumer Data Right’ (‘CDR’) to the banking sector through Open Banking regulation. Under Open Banking, TPPs can access customers’ banking data that allows the TPPs to tailor their products and services to meet customer needs at a more competitive price. This facilitated access and use of customer data will promote innovation by providing opportunities for new products and business models to emerge and grow. However, the success of Open Banking depends on the willingness of the customers to share their data, so the regulators have augmented the protection of data by introducing new privacy safeguards to instill confidence and trust in the system. The dilemma in policymaking is that, on the one hand, lenient data privacy laws will help the flow of information, but at the risk of individuals’ loss of privacy, on the other hand, stringent laws that adequately protect privacy may dissuade innovation. Using theoretical and doctrinal methods, this paper examines whether the privacy safeguards under Open Banking will add to the compliance burden of the participating financial institutions, resulting in the undesirable effect of stifling other policy objectives such as innovation. The contribution of this research is three-fold. In the emerging field of customer data sharing, this research is one of the few academic studies on the objectives and impact of Open Banking in the Australian context. Additionally, Open Banking is still in the early stages of implementation, so this research traces the evolution of Open Banking through policy debates regarding the desirability of customer data-sharing. Finally, the research focuses not only on the customers’ data privacy and juxtaposes it with another important objective of promoting innovation, but it also highlights the critical issues facing the data-sharing regime. This paper argues that while it is challenging to develop a regulatory framework for protecting data privacy without impeding innovation and jeopardising yet unknown opportunities, data privacy and innovation promote different aspects of customer welfare. This paper concludes that if a regulation is appropriately designed and implemented, the benefits of data-sharing will outweigh the cost of compliance with the CDR.

Keywords: consumer data right, innovation, open banking, privacy safeguards

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Authors: Ashraf M. Khalifa, Hwat Bing So, Greg Maddocks

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Changes to the mining environmental approvals process in Queensland have been rolled out under the MERFP Act (2018). This includes requirements for a Progressive Rehabilitation and Closure Plan (PRC Plan). Key considerations of the landform design report within the PRC Plan must include: (i) identification of materials available for landform rehabilitation, including their ability to achieve the required landform design outcomes, (ii) erosion assessments to determine landform heights, gradients, profiles, and material placement, (iii) slope profile design considering the interactions between soil erodibility, rainfall erosivity, landform height, gradient, and vegetation cover to identify acceptable erosion rates over a long-term average, (iv) an analysis of future stability based on the factors described above e.g., erosion and /or landform evolution modelling. ACARP funded an extensive and thorough erosion assessment program using rainfall simulators from 1998 to 2010. The ACARP program included laboratory assessment of 35 soil and spoil samples from 16 coal mines and samples from a gold mine in Queensland using 3 x 0.8 m laboratory rainfall simulator. The reliability of the laboratory rainfall simulator was verified through field measurements using larger flumes 20 x 5 meters and catchment scale measurements at three sites (3 different catchments, average area of 2.5 ha each). Soil cover systems are a primary component of a constructed mine landform. The primary functions of a soil cover system are to sustain vegetation and limit the infiltration of water and oxygen into underlying reactive mine waste. If the external surface of the landform erodes, the functions of the cover system cannot be maintained, and the cover system will most likely fail. Assessing a constructed landform’s potential ‘long-term’ erosion stability requires defensible erosion rate thresholds below which rehabilitation landform designs are considered acceptably erosion-resistant or ‘stable’. The process used to quantify erosion rates using rainfall simulators (flumes) to measure rill and inter-rill erosion on bulk samples under laboratory conditions or on in-situ material under field conditions will be explained.

Keywords: open-cut, mining, erosion, rainfall simulator

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Authors: Laura Gleason, Sahithi Talasila, Lauren Banner, Ladan Afifi, Neda Nikbakht

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Primary cutaneous anaplastic large cell lymphoma (pcALCL) accounts for 9% of all cutaneous T-cell lymphomas. pcALCL is classically characterized as a solitary papulonodule that often enlarges, ulcerates, and can be locally destructive, but overall exhibits an indolent course with overall 5-year survival estimated to be 90%. Distinguishing pcALCL from systemic ALCL (sALCL) is essential as sALCL confers a poorer prognosis with average 5-year survival being 40-50%. Although extremely rare, there have been several cases of ALK-positive ALCL diagnosed on skin biopsy without evidence of systemic involvement, which poses several challenges in the classification, prognostication, treatment, and follow-up of these patients. Objectives: We present a case of cutaneous ALK-positive ALCL without evidence of systemic involvement, and a narrative review of the literature to further characterize that ALK-positive ALCL limited to the skin is a distinct variant with a unique presentation, history, and prognosis. A 30-year-old woman presented for evaluation of an erythematous-violaceous papule present on her right chest for two months. With the development of multifocal disease and persistent lymphadenopathy, a bone marrow biopsy and lymph node excisional biopsy were performed to assess for systemic disease. Both biopsies were unrevealing. The patient was counseled on pursuing systemic therapy consisting of Brentuximab, Cyclophosphamide, Doxorubicin, and Prednisone given the concern for sALCL. Apropos of the patient we searched for clinically evident, cutaneous ALK-positive ALCL cases, with and without systemic involvement, in the English literature. Risk factors, such as tumor location, number, size, ALK localization, ALK translocations, and recurrence, were evaluated in cases of cutaneous ALK-positive ALCL. The majority of patients with cutaneous ALK-positive ALCL did not progress to systemic disease. The majority of cases that progressed to systemic disease in adults had recurring skin lesions and cytoplasmic localization of ALK. ALK translocations did not influence disease progression. Mean time to disease progression was 16.7 months, and significant mortality (50%) was observed in those cases that progressed to systemic disease. Pediatric cases did not exhibit a trend similar to adult cases. In both the adult and pediatric cases, a subset of cutaneous-limited ALK-positive ALCL were treated with chemotherapy. All cases treated with chemotherapy did not progress to systemic disease. Apropos of an ALK-positive ALCL patient with clinical cutaneous limited disease in the histologic presence of systemic markers, we discussed the literature data, highlighting the crucial issues related to developing a clinical strategy to approach this rare subtype of ALCL. Physicians need to be aware of the overall spectrum of ALCL, including cutaneous limited disease, systemic disease, disease with NPM-ALK translocation, disease with ALK and EMA positivity, and disease with skin recurrence.

Keywords: anaplastic large cell lymphoma, systemic, cutaneous, anaplastic lymphoma kinase, ALK, ALCL, sALCL, pcALCL, cALCL

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Authors: Daniela Brioschi, Rovilson Mafalda, Silvia Titotto

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In the present days, packages are considered a fundamental element in the commercialization of products and services. A good package is capable of helping to attract new customers and also increasing a product’s purchase intent. In this scenario, packaging design emerges as an important tool, since products and design of their packaging are so interconnected that they are no longer seen as separate elements. Packaging design is, in fact, capable of generating desire for a product. The packaging market for cosmetics, especially makeup market, has also been experiencing an increasing level of sophistication and requirements. Considering packaging represents an important link of communication with the final user and plays a significant role on the sales process, it is of great importance that packages accomplish not only with functional requirements but also with the visual appeal. One of the possibilities for the design of packages and, in this context, packages for make-up, is the bioinspired design – or biomimicry. The bio-inspired design presents a promising paradigm for innovation in both design and sustainable design, by using biological system analogies to develop solutions. It has gained importance as a widely diffused movement in design for environmentally conscious development and is also responsible for several useful and innovative designs. As eye mascara packages are also part of the constant evolution on the design for cosmetics area and the traditional packages present the disadvantage of product drying along time, this project aims to develop a new and innovative package for this product, by using a selected bioinspired design methodology during the development process and also suitable computational tools. In order to guide the development process of the package, it was chosen the spiral methodology, conceived by The Biomimicry Institut, which consists of a reliable tool, since it was based on traditional design methodologies. The spiral design comprises identification, translation, discovery, abstraction, emulation and evaluation steps, that can work iteratively as the process develops as a spiral. As support tool for packaging, 3D modelling is being used by the software Inventor Autodesk Inventor 2018. Although this is an ongoing research, first results showed that spiral methodology design, together with Autodesk Inventor, consist of suitable instruments for the bio-inspired design process, and also nature proved itself to be an amazing and inexhaustible source of inspiration.

Keywords: bio-inspired design, design methodology, packaging, cosmetics

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Authors: Debamitra Chakravorty, Pratap K. Parida

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Cold-adapted proteases enhance wash performance in low-temperature laundry resulting in a reduction in energy consumption and wear of textiles and are also used in the dehairing process in leather industries. Unfortunately, the possible drawbacks of using cold-adapted proteases are their instability at higher temperatures. Therefore, proteases with broad temperature stability are required. Unfortunately, wild-type cold-adapted proteases exhibit instability at higher temperatures and thus have low shelf lives. Therefore, attempts to engineer cold-adapted proteases by protein engineering were made previously by directed evolution and random mutagenesis. The lacuna is the time, capital, and labour involved to obtain these variants are very demanding and challenging. Therefore, rational engineering for cold stability without compromising an enzyme's optimum pH and temperature for activity is the current requirement. In this work, mutations were rationally designed with the aid of high throughput computational methodology of network analysis, evolutionary conservation scores, and molecular dynamics simulations for Savinase from Bacillus lentus with the intention of rendering the mutants cold stable without affecting their temperature and pH optimum for activity. Further, an attempt was made to incorporate a mutation in the most stable mutant rationally obtained by this method to introduce oxidative stability in the mutant. Such enzymes are desired in detergents with bleaching agents. In silico analysis by performing 300 ns molecular dynamics simulations at 5 different temperatures revealed that these three mutants were found to be better in cold stability compared to the wild type Savinase from Bacillus lentus. Conclusively, this work shows that cold adaptation without losing optimum temperature and pH stability and additionally stability from oxidative damage can be rationally designed by in silico enzyme engineering. The key findings of this work were first, the in silico data of H5 (cold stable savinase) used as a control in this work, corroborated with its reported wet lab temperature stability data. Secondly, three cold stable mutants of Savinase from Bacillus lentus were rationally identified. Lastly, a mutation which will stabilize savinase against oxidative damage was additionally identified.

Keywords: cold stability, molecular dynamics simulations, protein engineering, rational design

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Authors: Amirreza Razzaghipour Sorkhab

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One of the most common disorders among humans is hearing impairment. This paper provides an evidence base that recovers understanding of Meniere’s disease and highlights the physical and mental health correlates of the disorder. Meniere's disease is more common in the elderly. The term idiopathic endolymphatic hydrops has been attributed to this disease by some in the previous. Meniere’s disease demonstrations a genetic tendency, and a family history is found in 10% of cases, with an autosomal dominant inheritance pattern. The COCH gene may be one of the hereditary factors contributing to Meniere’s disease, and the possibility of a COCH mutation should be considered in patients with Meniere’s disease symptoms. Should be considered Missense mutations in the COCH gene cause the autosomal dominant sensorineural hearing loss and vestibular disorder. Meniere’s disease is a complex, heterogeneous disorder of the inner ear and that is characterized by episodes of vertigo lasting from minutes to hours, fluctuating sensorineural hearing loss, tinnitus, and aural fullness. The existing evidence supports the suggestion that age and sleep disorder are risk factors for Meniere's disease. Many factors have been reported to precipitate the progress of Menier, including endolymphatic hydrops, immunology, viral infection, inheritance, vestibular migraine, and altered intra-labyrinthine fluid dynamics. Although there is currently no treatment that has a proven helpful effect on hearing levels or on the long-term evolution of the disease, however, in the primary stages, the hearing may improve among attacks, but a permanent hearing loss occurs in the majority of cases. Current publications have proposed a role for the intratympanic use of medicine, mostly aminoglycosides, for the control of vertigo. more than 85% of patients with Meniere's disease are helped by either changes in lifestyle and medical treatment or minimally aggressive surgical procedures such as intratympanic steroid therapy, intratympanic gentamicin therapy, and endolymphatic sac surgery. However, unilateral vestibular extirpation methods (intratympanic gentamicin, vestibular nerve section, or labyrinthectomy) are more predictable but invasive approaches to control the vertigo attacks. Medical therapy aimed at reducing endolymph volume, such as low-sodium diet, diuretic use, is the typical initial treatment.

Keywords: meniere's disease, endolymphatic hydrops, hearing loss, vertigo, tinnitus, COCH gene

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Authors: Animesh Pan, Geoffrey D. Bothun

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With the development of nanotechnology, research in multifunctional delivery systems has a new pace and dimension. An incipient challenge is to design an all-in-one delivery system that can be used for multiple purposes, including tumor targeting therapy, radio-frequency (RF-), near-infrared (NIR-), light-, or pH-induced controlled release, photothermal therapy (PTT), photodynamic therapy (PDT), and medical diagnosis. In this regard, various inorganic nanoparticles (NPs) are known to show great potential as the 'functional components' because of their fascinating and tunable physicochemical properties and the possibility of multiple theranostic modalities from individual NPs. Magnetic, luminescent, and plasmonic properties are the three most extensively studied and, more importantly biomedically exploitable properties of inorganic NPs. Although successful attempts of combining any two of them above mentioned functionalities have been made, integrating them in one system has remained challenge. Keeping those in mind, controlled designs of complex colloidal nanoparticle system are one of the most significant challenges in nanoscience and nanotechnology. Therefore, systematic and planned studies providing better revelation are demanded. We report a multifunctional delivery platform-based liposome loaded with drug, iron-oxide magnetic nanoparticles (MNPs), and a gold shell on the surface of liposomes, were synthesized using a lipid with polyelectrolyte (layersomes) templating technique. MNPs and the anti-cancer drug doxorubicin (DOX) were co-encapsulated inside liposomes composed by zwitterionic phophatidylcholine and anionic phosphatidylglycerol using reverse phase evaporation (REV) method. The liposomes were coated with positively charge polyelectrolyte (poly-L-lysine) to enrich the interface with gold anion, exposed to a reducing agent to form a gold nanoshell, and then capped with thio-terminated polyethylene glycol (SH-PEG2000). The core-shell nanostructures were characterized by different techniques like; UV-Vis/NIR scanning spectrophotometer, dynamic light scattering (DLS), transmission electron microscope (TEM). This multifunctional system achieves a variety of functions, such as radiofrequency (RF)-triggered release, chemo-hyperthermia, and NIR laser-triggered for photothermal therapy. Herein, we highlight some of the remaining major design challenges in combination with preliminary studies assessing therapeutic objectives. We demonstrate an efficient loading and delivery system to significant cell death of human cancer cells (A549) with therapeutic capabilities. Coupled with RF and NIR excitation to the doxorubicin-loaded core-shell nanostructure helped in securing targeted and controlled drug release to the cancer cells. The present core-shell multifunctional system with their multimodal imaging and therapeutic capabilities would be eminent candidates for cancer theranostics.

Keywords: cancer thernostics, multifunctional nanostructure, photothermal therapy, radiofrequency targeting

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Authors: Murad Ali, Shoji Arai, Mohamed Khedr, Mukhtar Nasher, Shawki Nasr

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The Wadi Bayhan area of southeastern Yemen is about 60 km NW of Al-Bayda city in the Al-Bayda uplift terrane at the southeast margin of the Arabian-Nubian Shield. Intrusion of alkali gabbro into carbonate rocks apparently produced an 8m to 10 m thick reaction zone at the contact. This had been identified as nepheline pyroxenite. We have observed this to be mineralogically zoned with calc-silicate assemblages (e.g. pyroxene, calcite, spinel, garnet and melilite). The presence of melilite implies a skarn. The sinuous embayed pyroxenite-skarn contact, the presence of skarn minerals in pyroxenite, and textural evidence for growth of calc-silicate skarn by replacement of both carbonate rocks and solid pyroxenite indicate that reaction involved assimilation of carbonate wall rock by magma and loss of Al and Si to the skarn. Textural relationships between minerals provide evidence for a metasomatic development of the skarn at the expense of the pyroxenite. This process, related to the circulation of fluids equilibrated with carbonates, is responsible for those pyroxenite-spinel (± calcite) skarns. The uneven modal distribution of euhedral pyroxenite and enveloping nepheline in pyroxenite, the restricted occurrence of alkali gabbro as dikes in pyroxenite and skarn and the leucocratic matrix of pyroxenite suggest that pyroxenite represents an accumulation of titanaugite cemented by an alkali-rich residual magma and that alkali gabbro represents a part of the residual contaminated magma that was squeezed out of the pyroxene crystal mush. Carbonate assimilation is modeled by reaction of calcite and magmatic plagioclase, which results in resorption of plagioclase, growth of pyroxene enriched in Ca, Fe, Ti, and Al, and solution of nepheline in residual contaminated magma. The composition of nepheline pyroxenite evolved by addition of Ca from dissolved carbonate rocks, loss of Al and Si to skarn, and local segregation of solid pyroxene and alkali gabbro magma. The predominance of pyroxenite among contaminated rocks and their restriction to a large zone along the intrusive contact provide little evidence for the genesis of a significant volume of alkaline magmatic surroundings by carbonate assimilation.

Keywords: Yemen, Wadi Bayhan, skarn, pyroxenite, carbonatite, metasomatic

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