Search results for: two phase fluid flow

Authors: Deon Bezuidenhout

Abstract:

Pre-seeding with autologous endothelial cells improves the long-term patency of synthetic vascular grafts levels obtained with autografts, but is limited to a single centre due to resource, time and other constraints. Spontaneous in vivo endothelialization would obviate the need for pre-seeding, but has been shown to be absent in man due to limited transanastomotic and fallout healing, and the lack of transmural ingrowth due to insufficient porosity. Two types of graft scaffolds with increased interconnected porosity for improved tissue ingrowth and healing are thus proposed and described. Foam-type polyurethane (PU) scaffolds with small, medium and large, interconnected pores were made by phase inversion and spherical porogen extraction, with and without additional surface modification with covalently attached heparin and subsequent loading with and delivery of growth factors. Fibrillar scaffolds were made either by standard electrospinning using degradable PU (Degrapol®), or by dual electrospinning using non-degradable PU. The latter process involves sacrificial fibres that are co-spun with structural fibres and subsequently removed to increased porosity and pore size. Degrapol samples were subjected to in vitro degradation, and all scaffold types were evaluated in vivo for tissue ingrowth and vascularization using rat subcutaneous model. The foam scaffolds were additionally evaluated in a circulatory (rat infrarenal aortic interposition) model that allows for the grafts to be anastomotically and/or ablumenally isolated to discern and determine endothelialization mode. Foam-type grafts with large (150 µm) pores showed improved subcutaneous healing in terms of vascularization and inflammatory response over smaller pore sizes (60 and 90µm), and vascularization of the large porosity scaffolds was significantly increased by more than 70% by heparin modification alone, and by 150% to 400% when combined with growth factors. In the circulatory model, extensive transmural endothelialization (95±10% at 12 w) was achieved. Fallout healing was shown to be sporadic and limited in groups that were ablumenally isolated to prevent transmural ingrowth (16±30% wrapped vs. 80±20% control; p<0.002). Heparinization and GF delivery improved both mural vascularization and lumenal endothelialization. Degrapol electrospun scaffolds showed decrease in molecular mass and corresponding tensile strength over the first 2 weeks, but very little decrease in mass over the 4w test period. Studies on the effect of tissue ingrowth with and without concomitant degradation of the scaffolds, are being used to develop material models for the finite element modelling. In the case of the dual-spun scaffolds, the PU fibre fraction could be controlled shown to vary linearly with porosity (P = −0.18FF +93.5, r2=0.91), which in turn showed inverse linear correlation with tensile strength and elastic modulus (r2 > 0.96). Calculated compliance and burst pressures of the scaffolds increased with fibre fraction, and compliances matching the human popliteal artery (5-10 %/100 mmHg), and high burst pressures (> 2000 mmHg) could be achieved. Increasing porosity (76 to 82 and 90%) resulted in increased tissue ingrowth from 33±7 to 77±20 and 98±1% after 28d. Transmural endothelialization of highly porous foamed grafts is achievable in a circulatory model, and the enhancement of porosity and tissue ingrowth may hold the key the development of spontaneously endothelializing electrospun grafts.

Keywords: electrospinning, endothelialization, porosity, scaffold, vascular graft

Procedia PDF Downloads 292

Authors: Chirag Raval, Jimmy Toussaint, Tieuvi Nguyen, Hadi Fadaifard, George Wolberg, Steven Quarfordt, Kung-ming Jan, David S. Rumschitzki

Abstract:

Numerous studies examine aquaporins’ role in osmotic water transport in various systems but virtually none focus on aquaporins’ role in hydrostatically-driven water transport involving mammalian cells save for our laboratory’s recent study of aortic endothelial cells. Here we investigate aquaporin-1 expression and function in the aortic endothelium in two high-renin rat models of hypertension, the spontaneously hypertensive genomically altered Wystar-Kyoto rat variant and Sprague-Dawley rats made hypertensive by two kidney, one clip Goldblatt surgery. We measured aquaporin-1 expression in aortic endothelial cells from whole rat aortas by quantitative immunohistochemistry, and function by measuring the pressure driven hydraulic conductivities of excised rat aortas with both intact and denuded endothelia on the same vessel. We use them to calculate the effective intimal hydraulic conductivity, which is a combination of endothelial and subendothelial components. We observed well-correlated enhancements in aquaporin-1 expression and function in both hypertensive rat models as well as in aortas from normotensive rats whose expression was upregulated by 2h forskolin treatment. Upregulated aquaporin-1 expression and function may be a response to hypertension that critically determines conduit artery vessel wall viability and long-term susceptibility to atherosclerosis. Numerous studies examine aquaporins’ role in osmotic water transport in various systems but virtually none focus on aquaporins’ role in hydrostatically-driven water transport involving mammalian cells save for our laboratory’s recent study of aortic endothelial cells. Here we investigate aquaporin-1 expression and function in the aortic endothelium in two high-renin rat models of hypertension, the spontaneously hypertensive genomically altered Wystar-Kyoto rat variant and Sprague-Dawley rats made hypertensive by two kidney, one clip Goldblatt surgery. We measured aquaporin-1 expression in aortic endothelial cells from whole rat aortas by quantitative immunohistochemistry, and function by measuring the pressure driven hydraulic conductivities of excised rat aortas with both intact and denuded endothelia on the same vessel. We use them to calculate the effective intimal hydraulic conductivity, which is a combination of endothelial and subendothelial components. We observed well-correlated enhancements in aquaporin-1 expression and function in both hypertensive rat models as well as in aortas from normotensive rats whose expression was upregulated by 2h forskolin treatment. Upregulated aquaporin-1 expression and function may be a response to hypertension that critically determines conduit artery vessel wall viability and long-term susceptibility to atherosclerosis.

Keywords: acute hypertension, aquaporin-1, hydraulic conductivity, hydrostatic pressure, aortic endothelial cells, transcellular flow

Procedia PDF Downloads 222

Authors: Birgit A. A. Solem, Kristin Bentsen

Abstract:

Scholarly attention in entrepreneurship is currently directed towards understanding entrepreneurial venture creation as a process -the journey of new economic activities from nonexistence to existence often studied through flow- or network models. To complement existing research on entrepreneurial venture creation with more interactivity-based research of organized activities, this study examines two pop-up stores as anchor events involving on-site activities of fifteen participating entrepreneurs launching their new ventures. The pop-up stores were arranged in two middle-sized Norwegian cities and contained different brand stores that brought together actors of sub-networks and communities executing venture creation activities. The pop-up stores became on-site arenas for the entrepreneurs to create, maintain, and rejuvenate their networks, at the same time as becoming venues for temporal coordination of activities involving existing and potential customers in their venture creation. In this work, we apply a conceptual framework based on frequently addressed dilemmas within entrepreneurship theory (discovery/creation, causation/effectuation) to further shed light on the broad aspect of on-site anchor event activities and their venture creation outcomes. The dilemma-based concepts are applied as an analytic toolkit to pursue answers regarding the nature of anchor event activities typically found within entrepreneurial venture creation and how these anchor event activities affect entrepreneurial venture creation outcomes. Our study combines researcher participation with 200 hours of observation and twenty in-depth interviews. Data analysis followed established guidelines for hermeneutic analysis and was intimately intertwined with ongoing data collection. Data was coded and categorized in NVivo 12 software, and iterated several times as patterns were steadily developing. Our findings suggest that core anchor event activities typically found within entrepreneurial venture creation are; a concept- and product experimentation with visitors, arrangements to socialize (evening specials, auctions, and exhibitions), store-in-store concepts, arranged meeting places for peers and close connection with municipality and property owners. Further, this work points to four main entrepreneurial venture creation outcomes derived from the core anchor event activities; (1) venture attention, (2) venture idea-realization, (3) venture collaboration, and (4) venture extension. Our findings show that, depending on which anchor event activities are applied, the outcomes vary. Theoretically, this study offers two main implications. First, anchor event activities are both discovered and created, following the logic of causation, at the same time as being experimental, based on “learning by doing” principles of effectuation during the execution. Second, our research enriches prior studies on venture creation as a process. In this work, entrepreneurial venture creation activities and outcomes are understood through pop-up stores as on-site anchor event arenas, particularly suitable for interactivity-based research requested by the entrepreneurship field. This study also reveals important managerial implications, such as that entrepreneurs should allow themselves to find creative physical venture creation arenas (e.g., pop-up stores, showrooms), as well as collaborate with partners when discovering and creating concepts and activities based on new ideas. In this way, they allow themselves to both strategically plan for- and continually experiment with their venture.

Keywords: anchor event, interactivity-based research, pop-up store, entrepreneurial venture creation

Procedia PDF Downloads 84

Authors: Irina Deputat, Anatoly Gribanov, Yuliya Dzhos, Alexandra Nekhoroshkova, Tatyana Yemelianova, Irina Bolshevidtseva, Irina Deryabina, Yana Kereush, Larisa Startseva, Tatyana Bagretsova, Irina Ikonnikova

Abstract:

In the modern world the number of elderly people increases. Preservation of functionality of an organism in the elderly becomes very important now. During aging the higher cortical functions such as feelings, perception, attention, memory, and ideation are gradual decrease. It is expressed in the rate of information processing reduction, volume of random access memory loss, ability to training and storing of new information decrease. Perspective directions in studying of aging neurophysiological parameters are brain imaging: computer electroencephalography, neuroenergy mapping of a brain, and also methods of studying of a neurodynamic brain processes. Research aim – to study features of a brain aging in elderly people by electroencephalogram (EEG) and the DC-potential level. We examined 130 people aged 55 - 74 years that did not have psychiatric disorders and chronic states in a decompensation stage. EEG was recorded with a 128-channel GES-300 system (USA). EEG recordings are collected while the participant sits at rest with their eyes closed for 3 minutes. For a quantitative assessment of EEG we used the spectral analysis. The range was analyzed on delta (0,5–3,5 Hz), a theta - (3,5–7,0 Hz), an alpha 1-(7,0–11,0 Hz) an alpha 2-(11–13,0 Hz), beta1-(13–16,5 Hz) and beta2-(16,5–20 Hz) ranges. In each frequency range spectral power was estimated. The 12-channel hardware-software diagnostic ‘Neuroenergometr-KM’ complex was applied for registration, processing and the analysis of a brain constant potentials level. The DC-potential level registered in monopolar leads. It is revealed that the EEG of elderly people differ in higher rates of spectral power in the range delta (р < 0,01) and a theta - (р < 0,05) rhythms, especially in frontal areas in aging. By results of the comparative analysis it is noted that elderly people 60-64 aged differ in higher values of spectral power alfa-2 range in the left frontal and central areas (р < 0,05) and also higher values beta-1 range in frontal and parieto-occipital areas (р < 0,05). Study of a brain constant potential level distribution revealed increase of total energy consumption on the main areas of a brain. In frontal leads we registered the lowest values of constant potential level. Perhaps it indicates decrease in an energy metabolism in this area and difficulties of executive functions. The comparative analysis of a potential difference on the main assignments testifies to unevenness of a lateralization of a brain functions at elderly people. The results of a potential difference between right and left hemispheres testify to prevalence of the left hemisphere activity. Thus, higher rates of functional activity of a cerebral cortex are peculiar to people of early advanced age (60-64 years) that points to higher reserve opportunities of central nervous system. By 70 years there are age changes of a cerebral power exchange and level of electrogenesis of a brain which reflect deterioration of a condition of homeostatic mechanisms of self-control and the program of processing of the perceptual data current flow.

Keywords: brain, DC-potential level, EEG, elderly people

Procedia PDF Downloads 478

Authors: Sofia N. Gonçalves, Duarte M. S. Albuquerque, José C. F. Pereira

Abstract:

The energy transition is spurred by structural changes in energy demand, supply, and prices. Microwave technology was first proposed as a faster alternative for cooking food. It was found that food heated instantly when interacting with high-frequency electromagnetic waves. The dielectric properties account for a material’s ability to absorb electromagnetic energy and dissipate this energy in the form of heat. Many energy-intense industries could benefit from electromagnetic heating since many of the raw materials are dielectric at high temperatures. Limestone sedimentary rock is a dielectric material intensively used in the cement industry to produce unslaked lime. A numerical 3D model was implemented in COMSOL Multiphysics to study the limestone continuous processing under microwave heating. The model solves the two-way coupling between the Energy equation and Maxwell’s equations as well as the coupling between heat transfer and chemical interfaces. Complementary, a controller was implemented to optimize the overall heating efficiency and control the numerical model stability. This was done by continuously matching the cavity impedance and predicting the required energy for the system, avoiding energy inefficiencies. This controller was developed in MATLAB and successfully fulfilled all these goals. The limestone load influence on thermal decomposition and overall process efficiency was the main object of this study. The procedure considered the Verification and Validation of the chemical kinetics model separately from the coupled model. The chemical model was found to correctly describe the chosen kinetic equation, and the coupled model successfully solved the equations describing the numerical model. The interaction between flow of material and electric field Poynting vector revealed to influence limestone decomposition, as a result from the low dielectric properties of limestone. The numerical model considered this effect and took advantage from this interaction. The model was demonstrated to be highly unstable when solving non-linear temperature distributions. Limestone has a dielectric loss response that increases with temperature and has low thermal conductivity. For this reason, limestone is prone to produce thermal runaway under electromagnetic heating, as well as numerical model instabilities. Five different scenarios were tested by considering a material fill ratio of 30%, 50%, 65%, 80%, and 100%. Simulating the tube rotation for mixing enhancement was proven to be beneficial and crucial for all loads considered. When uniform temperature distribution is accomplished, the electromagnetic field and material interaction is facilitated. The results pointed out the inefficient development of the electric field within the bed for 30% fill ratio. The thermal efficiency showed the propensity to stabilize around 90%for loads higher than 50%. The process accomplished a maximum microwave efficiency of 75% for the 80% fill ratio, sustaining that the tube has an optimal fill of material. Electric field peak detachment was observed for the case with 100% fill ratio, justifying the lower efficiencies compared to 80%. Microwave technology has been demonstrated to be an important ally for the decarbonization of the cement industry.

Keywords: CFD numerical simulations, efficiency optimization, electromagnetic heating, impedance matching, limestone continuous processing

Procedia PDF Downloads 167

Authors: Rachid Essamoud, Abdelkrim Afenzar, Ahmed Belqadi

Abstract:

During the Early Mesozoic, the northwestern part of the African continent was affected by initial fracturing associated with the early stages of the opening of the Central Atlantic (Atlantic Rift). During this rifting phase, the Moroccan Meseta experienced an extensive tectonic regime. This extension favored the formation of a set of rift-type basins, including the Mohammedia-Benslimane-ElGara-Berrechid basin. Thus, it is essential to know the nature of the deposits in this basin and their evolution over time as well as their relationship with the basaltic effusion of the Central Atlantic Magmatic Province (CAMP). These deposits are subdivided into two large series: The Lower clay-salt series attributed to the Triassic and the Upper clay-salt series attributed to the Liassic. The two series are separated by the Upper Triassic-Lower Liassic basaltic complex. The detailed sedimentological analysis made it possible to characterize four mega-sequences, fifteen types of facies and eight architectural elements and facies associations in the Triassic series. A progressive decrease observed in paleo-slope over time led to the evolution of the paleoenvironment from a proximal system of alluvial fans to a braided fluvial style, then to an anastomosed system. These environments eventually evolved into an alluvial plain associated with a coastal plain where playa lakes, mudflats and lagoons had developed. The pure and massive halitic facies at the top of the series probably indicate an evolution of the depositional environment towards a shallow subtidal environment. The presence of these evaporites indicates a climate that favored their precipitation, in this case, a fairly hot and humid climate. The sedimentological analysis of the supra-basaltic part shows that during the Lower Liassic, the paleopente after basaltic effusion remained weak with distal environments. The faciological analysis revealed the presence of four major sandstone, silty, clayey and evaporitic lithofacies organized in two mega-sequences: the sedimentation of the first rock-salt mega-sequence took place in a brine depression system free, followed by saline mudflats under continental influences. The upper clay mega-sequence displays facies documenting sea level fluctuations from the final transgression of the Tethys or the opening Atlantic. Saliferous sedimentation is therefore favored from the Upper Triassic, but experienced a sudden rupture by the emission of basaltic flows which are interstratified in the azoic salt clays of very shallow seas. This basaltic emission which belongs to the CAMP would come from a fissural volcanism probably carried out through transfer faults located in the NW and SE of the basin. Their emplacement is probably subaquatic to subaerial. From a chronological and paleogeographic point of view, this main volcanism, dated between the Upper Triassic and the Lower Liassic (180-200 MA), is linked to the fragmentation of Pangea and managed by a progressive expansion triggered in the West in close relation with the initial phases of Central Atlantic rifting and seems to coincide with the major mass extinction at the Triassic-Jurassic boundary.

Keywords: Basalt, CAMP, Liassic, sedimentology, Triassic, Morocco

Procedia PDF Downloads 67

Authors: George Kyriakopoulos, Photini Pazartzis, Anthi Koskina, Crystalie Bourcha

Abstract:

The need for securing safe access to and return from outer space, as well as ensuring the viability of outer space operations, maintains vivid the debate over the promotion of organization of space traffic through a Space Traffic Management System (STM). The proliferation of outer space activities in recent years as well as the dynamic emergence of the private sector has gradually resulted in a diverse universe of actors operating in outer space. The said developments created an increased adverse impact on outer space sustainability as the case of the growing number of space debris clearly demonstrates. The above landscape sustains considerable threats to outer space environment and its operators that need to be addressed by a combination of scientific-technological measures and regulatory interventions. In this context, recourse to recent technological advancements and, in particular, to Artificial Intelligence (AI) and machine learning systems, could achieve exponential results in promoting space traffic management with respect to collision avoidance as well as launch and re-entry procedures/phases. New technologies can support the prospects of a successful space traffic management system at an international scale by enabling, inter alia, timely, accurate and analytical processing of large data sets and rapid decision-making, more precise space debris identification and tracking and overall minimization of collision risks and reduction of operational costs. What is more, a significant part of space activities (i.e. launch and/or re-entry phase) takes place in airspace rather than in outer space, hence the overall discussion also involves the highly developed, both technically and legally, international (and national) Air Traffic Management System (ATM). Nonetheless, from a regulatory perspective, the use of AI for the purposes of space traffic management puts forward implications that merit particular attention. Key issues in this regard include the delimitation of AI-based activities as space activities, the designation of the applicable legal regime (international space or air law, national law), the assessment of the nature and extent of international legal obligations regarding space traffic coordination, as well as the appropriate liability regime applicable to AI-based technologies when operating for space traffic coordination, taking into particular consideration the dense regulatory developments at EU level. In addition, the prospects of institutionalizing international cooperation and promoting an international governance system, together with the challenges of establishment of a comprehensive international STM regime are revisited in the light of intervention of AI technologies. This paper aims at examining regulatory implications advanced by the use of AI technology in the context of space traffic management operations and its key correlating concepts (SSA, space debris mitigation) drawing in particular on international and regional considerations in the field of STM (e.g. UNCOPUOS, International Academy of Astronautics, European Space Agency, among other actors), the promising advancements of the EU approach to AI regulation and, last but not least, national approaches regarding the use of AI in the context of space traffic management, in toto. Acknowledgment: The present work was co-funded by the European Union and Greek national funds through the Operational Program "Human Resources Development, Education and Lifelong Learning " (NSRF 2014-2020), under the call "Supporting Researchers with an Emphasis on Young Researchers – Cycle B" (MIS: 5048145).

Keywords: artificial intelligence, space traffic management, space situational awareness, space debris

Procedia PDF Downloads 245

Authors: Alireza Shams, Ali Zamanian, Atefehe Shamosi, Farnaz Ghorbani

Abstract:

Introduction: Although the application of a new strategy remains a remarkable challenge for treatment of disabilities due to neuronal defects, progress in Nanomedicine and tissue engineering, suggesting the new medical methods. One of the promising strategies for reconstruction and regeneration of nervous tissue is replacing of lost or damaged cells by specific scaffolds after Compressive, ischemic and traumatic injuries of central nervous system. Furthermore, ultrastructure, composition, and arrangement of tissue scaffolds are effective on cell grafts. We followed implantation and differentiation of mesenchyme stem cells to neural cells on Gelatin Polylactic-co-glycolic acid (PLGA) scaffolds coated with iron nanoparticles. The aim of this study was to evaluate the capability of stem cells to differentiate into motor neuron-like cells under topographical cues and morphogenic factors. Methods and Materials: Bone marrow mesenchymal stem cells (BMMSCs) was obtained by primary cell culturing of adult rat bone marrow got from femur bone by flushing method. BMMSCs were incubated with DMEM/F12 (Gibco), 15% FBS and 100 U/ml pen/strep as media. Then, BMMSCs seeded on Gel/PLGA scaffolds and tissue culture (TCP) polystyrene embedded and incorporated by Fe Nano particles (FeNPs) (Fe3o4 oxide (M w= 270.30 gr/mol.). For neuronal differentiation, 2×10 5 BMMSCs were seeded on Gel/PLGA/FeNPs scaffolds was cultured for 7 days and 0.5 µ mol. Retinoic acid, 100 µ mol. Ascorbic acid,10 ng/ml. Basic fibroblast growth factor (Sigma, USA), 250 μM Iso butyl methyl xanthine, 100 μM 2-mercaptoethanol, and 0.2 % B27 (Invitrogen, USA) added to media. Proliferation of BMMSCs was assessed by using MTT assay for cell survival. The morphology of BMMSCs and scaffolds was investigated by scanning electron microscopy analysis. Expression of neuron-specific markers was studied by immunohistochemistry method. Data were analyzed by analysis of variance, and statistical significance was determined by Turkey’s test. Results: Our results revealed that differentiation and survival of BMMSCs into motor neuron-like cells on Gel/PLGA/FeNPs as a biocompatible and biodegradable scaffolds were better than those cultured in Gel/PLGA in absence of FeNPs and TCP scaffolds. FeNPs had raised physical power but decreased capacity absorption of scaffolds. Well defined oriented pores in scaffolds due to FeNPs may activate differentiation and synchronized cells as a mechanoreceptor. Induction effects of magnetic FeNPs by One way flow of channels in scaffolds help to lead the cells and can facilitate direction of their growth processes. Discussion: Progression of biological properties of BMMSCs and the effects of FeNPs spreading under magnetic field was evaluated in this investigation. In vitro study showed that the Gel/PLGA/FeNPs scaffold provided a suitable structure for motor neuron-like cells differentiation. This could be a promising candidate for enhancing repair and regeneration in neural defects. Dynamic and static magnetic field for inducing and construction of cells can provide better results for further experimental studies.

Keywords: differentiation, mesenchymal stem cells, nano particles, neuronal defects, Scaffolds

Procedia PDF Downloads 161

Authors: Rafia S. Al-lamki, Jun Wang, Simon Pacey, Jordan Pober, John R. Bradley

Abstract:

Tumor necrosis factor alpha (TNF), signaling through TNFR2, may act an autocrine growth factor for renal tubular epithelial cells. Clear cell renal carcinomas (ccRCC) contain cancer stem cells (CSCs) that give rise to progeny which form the bulk of the tumor. CSCs are rarely in cell cycle and, as non-proliferating cells, resist most chemotherapeutic agents. Thus, recurrence after chemotherapy may result from the survival of CSCs. Therapeutic targeting of both CSCs and the more differentiated bulk tumor populations may provide a more effective strategy for treatment of RCC. In this study, we hypothesized that TNFR2 signaling will induce CSCs in ccRCC to enter cell cycle so that treatment with ligands that engage TNFR2 will render CSCs susceptible to chemotherapy. To test this hypothesis, we have utilized wild-type TNF (wtTNF) or specific muteins selective for TNFR1 (R1TNF) or TNFR2 (R2TNF) to treat either short-term organ cultures of ccRCC and adjacent normal kidney (NK) tissue or cultures of CD133+ cells isolated from ccRCC and adjacent NK, hereafter referred to as stem cell-like cells (SCLCs). The effect of cyclophosphamide (CP), currently an effective anticancer agent, was tested on CD133+SCLCs from ccRCC and NK before and after R2TNF treatment. Responses to TNF were assessed by flow cytometry (FACS), immunofluorescence, and quantitative real-time PCR, TUNEL, and cell viability assays. Cytotoxic effect of CP was analyzed by Annexin V and propidium iodide staining with FACS. In addition, we assessed the effect of TNF on isolated SCLCs differentiation using a three-dimensional (3D) culture system. Clinical samples of ccRCC contain a greater number SCLCs compared to NK and the number of SCSC increases with higher tumor grade. Isolated SCLCs show expression of stemness markers (oct4, Nanog, Sox2, Lin28) but not differentiation markers (cytokeratin, CD31, CD45, and EpCAM). In ccRCC organ cultures, wtTNF and R2TNF increase CD133 and TNFR2 expression and promote cell cycle entry whereas wtTNF and R1TNF increase TNFR1 expression and promote cell death of SCLCs. Similar findings are observed in SCLCs isolated from NK but the effect was greater in SCLCs isolated from ccRCC. Application of CP distinctly triggered apoptotic and necrotic cell death in SLCSs pre-treatment with R2TNF as compared to CP treatment alone, with SCLCs from ccRCC more sensitive to CP compared to SLCS from NK. Furthermore, TNF promotes differentiation of SCLCs to an epithelial phenotype in 3D cultures, confirmed by cytokeratin expression and loss of stemness markers Nanog and Sox2. The differentiated cells show positive expression of TNF and TNFR2. These findings provide evidence that selective engagement of TNFR2 drive CSCs to cell proliferation/differentiation, and targeting of cycling cells with TNFR2 agonist in combination with anti-cancer agents may be a potential therapy for RCC.

Keywords: cancer stem cells, ccRCC, cell cycle, cell death, TNF, TNFR1, TNFR2, CD133

Procedia PDF Downloads 259

Authors: Luc Beal

Abstract:

Introduction. Among the stakeholders involved in the tourist decision-making process, the accommodation provider has the potential to play a crucial role in raising awareness, disseminating information, and thus influencing the tourists’ choice of transportation. Since the early days of tourism, the accommodation provider has consistently served as the primary point of contact with the destination, and consequently, as the primary source of information for visitors. By offering accommodation and hospitality, the accommodation provider has evolved into a trusted third party, functioning as an 'ambassador' capable of recommending the finest attractions and activities available at the destination. In contemporary times, when tourists plan their trips, they make a series of consecutive decisions, with the most important decision being to lock-in the accommodation reservation for the earliest days, so as to secure a safe arrival. Consequently, tourists place their trust in the accommodation provider not only for lodging but also for recommendations regarding restaurants, activities, and more. Thus, the latter has the opportunity to inform and influence tourists well in advance of their arrival, particularly during the booking phase, namely when it comes to selecting their mode of transportation. The pressing need to reduce greenhouse gas emissions within the tourism sector presents an opportunity to underscore the influence that accommodation providers have historically exerted on tourist decision-making . Methodology A participatory research, currently ongoing in south-western France, in collaboration with a nationwide hotel group and several destination management organizations, aims at examining the factors that determine the ability of accommodation providers to influence tourist transportation choices. Additionally, the research seeks to identify the conditions that motivate accommodation providers to assume a proactive role, such as fostering customer loyalty, reduced distribution costs, and financial compensation mechanisms. A panel of hotels participated in a series of focus group sessions with tourists, with the objective of modeling the decision-making process of tourists regarding their choice of transportation mode and to identify and quantify the types and levels of incentives liable to encourage environmentally responsible choices. Individual interviews were also conducted with hotel staff, including receptionists and guest relations officers, to develop a framework for interactions with tourists during crucial decision-making moments related to transportation choices. The primary finding of this research indicates that financial incentives significantly outweigh symbolic incentives in motivating tourists to opt for eco-friendly modes of transportation. Another noteworthy result underscores the crucial impact of organizational conditions governing interactions with tourists both before and during their stay. These conditions greatly influence the ability to raise awareness at key decision-making moments and the possibility of gathering data about the chosen transportation mode during the stay. In conclusion, this research has led to the formulation of practical recommendations for accommodation providers and Destination Marketing Organizations (DMOs). These recommendations pertain to communication protocols with tourists, the collection of evidences confirming chosen transportation modes, and the implementation of necessary incentives. Through these measures, accommodation provider can assume a central role in guiding tourists towards making responsible choices in terms of transportation.

Keywords: accommodation provider, trusted third party, environmentally-friendly transportation, green house gas, tourist decision-making process

Procedia PDF Downloads 54

Authors: Shpetim Rezniqi

Abstract:

Financial Policies in the process of global crisis the current crisis has swept the world with special emphasis, most developed countries, those countries which have most gross -product world and you have a high level of living.Even those who are not experts can describe the consequences of the crisis to see the reality that is seen, but how far will it go this crisis is impossible to predict. Even the biggest experts have conjecture and large divergence, but agree on one thing: - The devastating effects of this crisis will be more severe than ever before and can not be predicted.Long time, the world was dominated economic theory of free market laws. With the belief that the market is the regulator of all economic problems. The market, as river water will flow to find the best and will find the necessary solution best. Therefore much less state market barriers, less state intervention and market itself is an economic self-regulation. Free market economy became the model of global economic development and progress, it transcends national barriers and became the law of the development of the entire world economy. Globalization and global market freedom were principles of development and international cooperation. All international organizations like the World Bank, states powerful economic, development and cooperation principles laid free market economy and the elimination of state intervention. The less state intervention much more freedom of action was this market- leading international principle. We live in an era of financial tragic. Financial markets and banking in particular economies are in a state of thy good, US stock markets fell about 40%, in other words, this time, was one of the darkest moments 5 since 1920. Prior to her rank can only "collapse" of the stock of Wall Street in 1929, technological collapse of 2000, the crisis of 1973 after the Yom Kippur war, while the price of oil quadrupled and famous collapse of 1937 / '38, when Europe was beginning World war II In 2000, even though it seems like the end of the world was the corner, the world economy survived almost intact. Of course, that was small recessions in the United States, Europe, or Japan. Much more difficult the situation was at crisis 30s, or 70s, however, succeeded the world. Regarding the recent financial crisis, it has all the signs to be much sharper and with more consequences. The decline in stock prices is more a byproduct of what is really happening. Financial markets began dance of death with the credit crisis, which came as a result of the large increase in real estate prices and household debt. It is these last two phenomena can be matched very well with the gains of the '20s, a period during which people spent fists as if there was no tomorrow. All is not away from the mouth of the word recession, that fact no longer a sudden and abrupt. But as much as the financial markets melt, the greater is the risk of a problematic economy for years to come. Thus, for example, the banking crisis in Japan proved to be much more severe than initially expected, partly because the assets which were based more loans had, especially the land that falling in value. The price of land in Japan is about 15 years that continues to fall. (ADRI Nurellari-Published in the newspaper "Classifieds"). At this moment, it is still difficult to çmosh to what extent the crisis has affected the economy and what would be the consequences of the crisis. What we know is that many banks will need more time to reduce the award of credit, but banks have this primary function, this means huge loss.

Keywords: globalisation, finance, crisis, recomandation, bank, credits

Procedia PDF Downloads 381

Authors: Anantha S. Babbili

Abstract:

This paper analyzes the current media practices dominant in global journalistic practices within the framework of world press theories of Libertarian, Authoritarian, Communist, and Social Responsibility to evaluate their efficacy in addressing their role in the coverage of the coronavirus, also known as COVID-19. The global media flows, determinants of news coverage, and international awareness and the Western view of the world will be critically analyzed within the context of the prevalent news values that underpin free press and media coverage of the world. While evaluating the global discourse paramount to a sustained and dispassionate understanding of world events, this paper proposes an ethical framework that brings clarity devoid of sensationalism, partisanship, right-wing and left-wing interpretations to a breaking and dangerous development of a pandemic. As the world struggles to contain the coronavirus pandemic with death climbing close to 6,000 from late January to mid-March, 2020, the populations of the developed as well as the developing nations are beset with news media renditions of the crisis that are contradictory, confusing and evoking anxiety, fear and hysteria. How are we to understand differing news standards and news values? What lessons do we as journalism and mass media educators, researchers, and academics learn in order to construct a better news model and structure of media practice that addresses science, health, and media literacy among media practitioners, journalists, and news consumers? As traditional media struggles to cover the pandemic to its audience and consumers, social media from which an increasing number of consumers get their news have exerted their influence both in a positive way and in a negative manner. Even as the world struggles to grasp the full significance of the pandemic, the World Health Organization (WHO) has been feverishly battling an additional challenge related to the pandemic in what it termed an 'infodemic'—'an overabundance of information, some accurate and some not, that makes it hard for people to find trustworthy sources and reliable guidance when they need it.' There is, indeed, a need for journalism and news coverage in times of pandemics that reflect social responsibility and ethos of public service journalism. Social media and high-tech information corporations, collectively termed GAMAF—Google, Apple, Microsoft, Amazon, and Facebook – can team up with reliable traditional media—newspapers, magazines, book publishers, radio and television corporates—to ease public emotions and be helpful in times of a pandemic outbreak. GAMAF can, conceivably, weed out sensational and non-credible sources of coronavirus information, exotic cures offered for sale on a quick fix, and demonetize videos that exploit peoples’ vulnerabilities at the lowest ebb. Credible news of utility delivered in a sustained, calm, and reliable manner serves people in a meaningful and helpful way. The world’s consumers of news and information, indeed, deserve a healthy and trustworthy news media – at least in the time of pandemic COVID-19. Towards this end, the paper will propose a practical model for news media and journalistic coverage during times of a pandemic.

Keywords: COVID-19, international news flow, social media, social responsibility

Procedia PDF Downloads 106

Authors: Michael Picard

Abstract:

This proposal offers to shed light on the changing legal geography of the global waste economy. Global waste recycling has become a multi-billion-dollar industry. NASDAQ predicts the emergence of a worldwide 1,296G$ waste management market between 2017 and 2022. Underlining this evolution, a new generation of preferential waste-trade agreements has emerged in the Pacific. In the last decade, Japan has concluded a series of bilateral treaties with Asian countries, and most recently with China. An agreement between Tokyo and Beijing was formalized on 7 May 2008, which forged an economic partnership on waste transfer and mining. The agreement set up International Recycling Zones, where certified recycling plants in China process industrial waste imported from Japan. Under the joint venture, Chinese companies salvage the embedded value from Japanese industrial discards, reprocess them and send them back to Japanese manufacturers, such as Mitsubishi and Panasonic. This circular economy is designed to convert surplus garbage into surplus value. Ever since the opening of Sino-Japanese eco-parks, millions of tons of plastic and e-waste have been exported from Japan to China every year. Yet, quite unexpectedly, China has recently closed its waste market to imports, jeopardizing Japan’s billion-dollar exports to China. China notified the WTO that, by the end of 2017, it would no longer accept imports of plastics and certain metals. Given China’s share of Japanese waste exports, a complete closure of China’s market would require Japan to find new uses for its recyclable industrial trash generated domestically every year. It remains to be seen how China will effectively implement its ban on waste imports, considering the economic interests at stake. At this stage, what remains to be clarified is whether China's ban on waste imports will negatively affect the recycling trade between Japan and China. What is clear, though, is the rapid transformation in the legal geography of waste mining in East-Asia. For decades, East-Asian waste trade had been tied up in an ‘ecologically unequal exchange’ between the Japanese core and the Chinese periphery. This global unequal waste distribution could be measured by the Environmental Stringency Index, which revealed that waste regulation was 39% weaker in the Global South than in Japan. This explains why Japan could legally export its hazardous plastic and electronic discards to China. The asymmetric flow of hazardous waste between Japan and China carried the colonial heritage of international law. The legal geography of waste distribution was closely associated to the imperial construction of an ecological trade imbalance between the Japanese source and the Chinese sink. Thus, China’s recent decision to ban hazardous waste imports is a sign of a broader ecological shift. As a global economic superpower, China announced to the world it would no longer be the planet’s junkyard. The policy change will have profound consequences on the global circulation of waste, re-routing global waste towards countries south of China, such as Vietnam and Malaysia. By the time the Berlin Conference takes place in May 2018, the presentation will be able to assess more accurately the effect of the Chinese ban on the transboundary movement of waste in Asia.

Keywords: Asia, ecological unequal exchange, global waste trade, legal geography

Procedia PDF Downloads 207

Authors: Huan Peng, Chenye Zeng, Zhao Wang

Abstract:

Alzheimer’s disease (AD) is an age-related neurodegenerative disease that is a leading cause of dementia syndromes and has become a huge burden on society and families. The main pathological features of AD involve excessive deposition of β-amyloid (Aβ) and Tau proteins in the brain, resulting in loss of neurons, expansion of neuroinflammation, and cognitive dysfunction in patients. Researchers have found effective drugs to clear the brain of error-accumulating proteins or to slow the loss of neurons, but their direct administration has key bottlenecks such as single-drug limitation, rapid blood clearance rate, impenetrable blood-brain barrier (BBB), and poor ability to target tissues and cells. Therefore, we are committed to seeking a suitable and efficient delivery system. Inspired by the possibility that exosomes may be involved in the secretion and transport mechanism of many signaling molecules or proteins in the brain, exosomes have attracted extensive attention as natural nanoscale drug carriers. We selected exosomes derived from bone marrow mesenchymal stem cells (MSC-EXO) with low immunogenicity and exosomes derived from hippocampal neurons (HT22-EXO) that may have excellent homing ability to overcome the deficiencies of oral or injectable pathways and bypass the BBB through nasal administration and evaluated their delivery ability and effect on AD. First, MSC-EXO and HT22 cells were isolated and cultured, and MSCs were identified by microimaging and flow cytometry. Then MSC-EXO and HT22-EXO were obtained by gradient centrifugation and qEV SEC separation column, and a series of physicochemical characterization were performed by transmission electron microscope, western blot, nanoparticle tracking analysis and dynamic light scattering. Next, exosomes labeled with lipophilic fluorescent dye were administered to WT mice and APP/PS1 mice to obtain fluorescence images of various organs at different times. Finally, APP/PS1 mice were administered intranasally with two exosomes 20 times over 40 days and 20 μL each time. Behavioral analysis and pathological section analysis of the hippocampus were performed after the experiment. The results showed that MSC-EXO and HT22-EXO were successfully isolated and characterized, and they had good biocompatibility. MSC-EXO showed excellent brain enrichment in APP/PS1 mice after intranasal administration, could improve the neuronal damage and reduce inflammation levels in the hippocampus of APP/PS1 mice, and the improvement effect was significantly better than HT22-EXO. However, intranasal administration of the two exosomes did not cause depression and anxious-like phenotypes in APP/PS1 mice, nor significantly improved the short-term or spatial learning and memory ability of APP/PS1 mice, and had no significant effect on the content of Aβ plaques in the hippocampus, which also meant that MSC-EXO could use their own advantages in combination with other drugs to clear Aβ plaques. The possibility of realizing highly effective non-invasive synergistic treatment for AD provides new strategies and ideas for clinical research.

Keywords: Alzheimer’s disease, exosomes derived from mesenchymal stem cell, intranasal administration, therapy-carrier dual roles

Procedia PDF Downloads 48

Authors: Kari Björn

Abstract:

Introduction of games has expanded the application area of computer-aided learning tools to wide variety of age groups of learners. Serious games engage the learners into a real-world -type of simulation and potentially enrich the learning experience. Institutional background of a Bachelor’s level engineering program in Information and Communication Technology is introduced, with detailed focus on one of its majors, Health Technology. As part of a Customer Oriented Software Application thematic semester, one particular course of “eHealth Business and Solutions” is described and reflected in a gamified framework. Learning a consistent view into vast literature of business management, strategies, marketing and finance in a very limited time enforces selection of topics relevant to the industry. Health Technology is a novel and growing industry with a growing sector in consumer wearable devices and homecare applications. The business sector is attracting new entrepreneurs and impatient investor funds. From engineering education point of view the sector is driven by miniaturizing electronics, sensors and wireless applications. However, the market is highly consumer-driven and usability, safety and data integrity requirements are extremely high. When the same technology is used in analysis or treatment of patients, very strict regulatory measures are enforced. The paper introduces a course structure using gamification as a tool to learn the most essential in a new market: customer value proposition design, followed by a market entry game. Students analyze the existing market size and pricing structure of eHealth web-service market and enter the market as a steering group of their company, competing against the legacy players and with each other. The market is growing but has its rules of demand and supply balance. New products can be developed with an R&D-investment, and targeted to market with unique quality- and price-combinations. Product cost structure can be improved by investing to enhanced production capacity. Investments can be funded optionally by foreign capital. Students make management decisions and face the dynamics of the market competition in form of income statement and balance sheet after each decision cycle. The focus of the learning outcome is to understand customer value creation to be the source of cash flow. The benefit of gamification is to enrich the learning experience on structure and meaning of financial statements. The paper describes the gamification approach and discusses outcomes after two course implementations. Along the case description of learning challenges, some unexpected misconceptions are noted. Improvements of the game or the semi-gamified teaching pedagogy are discussed. The case description serves as an additional support to new game coordinator, as well as helps to improve the method. Overall, the gamified approach has helped to engage engineering student to business studies in an energizing way.

Keywords: engineering education, integrated curriculum, learning experience, learning outcomes

Procedia PDF Downloads 238

Authors: Bidzina Matsaberidze, Anna Sikharulidze, Gia Sirbiladze, Bezhan Ghvaberidze

Abstract:

In the modern world emergency management decision support systems are actively used by state organizations, which are interested in extreme and abnormal processes and provide optimal and safe management of supply needed for the civil and military facilities in geographical areas, affected by disasters, earthquakes, fires and other accidents, weapons of mass destruction, terrorist attacks, etc. Obviously, these kinds of extreme events cause significant losses and damages to the infrastructure. In such cases, usage of intelligent support technologies is very important for quick and optimal location-transportation of emergency service in order to avoid new losses caused by these events. Timely servicing from emergency service centers to the affected disaster regions (response phase) is a key task of the emergency management system. Scientific research of this field takes the important place in decision-making problems. Our goal was to create an expert knowledge-based intelligent support system, which will serve as an assistant tool to provide optimal solutions for the above-mentioned problem. The inputs to the mathematical model of the system are objective data, as well as expert evaluations. The outputs of the system are solutions for Fuzzy Multi-Objective Emergency Location-Transportation Problem (FMOELTP) for disasters’ regions. The development and testing of the Intelligent Support System were done on the example of an experimental disaster region (for some geographical zone of Georgia) which was generated using a simulation modeling. Four objectives are considered in our model. The first objective is to minimize an expectation of total transportation duration of needed products. The second objective is to minimize the total selection unreliability index of opened humanitarian aid distribution centers (HADCs). The third objective minimizes the number of agents needed to operate the opened HADCs. The fourth objective minimizes the non-covered demand for all demand points. Possibility chance constraints and objective constraints were constructed based on objective-subjective data. The FMOELTP was constructed in a static and fuzzy environment since the decisions to be made are taken immediately after the disaster (during few hours) with the information available at that moment. It is assumed that the requests for products are estimated by homeland security organizations, or their experts, based upon their experience and their evaluation of the disaster’s seriousness. Estimated transportation times are considered to take into account routing access difficulty of the region and the infrastructure conditions. We propose an epsilon-constraint method for finding the exact solutions for the problem. It is proved that this approach generates the exact Pareto front of the multi-objective location-transportation problem addressed. Sometimes for large dimensions of the problem, the exact method requires long computing times. Thus, we propose an approximate method that imposes a number of stopping criteria on the exact method. For large dimensions of the FMOELTP the Estimation of Distribution Algorithm’s (EDA) approach is developed.

Keywords: epsilon-constraint method, estimation of distribution algorithm, fuzzy multi-objective combinatorial programming problem, fuzzy multi-objective emergency location/transportation problem

Procedia PDF Downloads 312

Authors: Yashas Bedre Raghavendra, Pim Vullers

Abstract:

This study presents the design and implementation of an abstract cryptographic coprocessor, leveraging AMBA(Advanced Microcontroller Bus Architecture) protocols - APB (Advanced Peripheral Bus) and AHB (Advanced High-performance Bus), to enable seamless integration with the main CPU(Central processing unit) and enhance the coprocessor’s algorithm flexibility. The primary objective is to create a versatile coprocessor that can execute various cryptographic algorithms, including ECC(Elliptic-curve cryptography), RSA(Rivest–Shamir–Adleman), and AES (Advanced Encryption Standard) while providing a robust and secure solution for modern secure embedded systems. To achieve this goal, the coprocessor is equipped with a tightly coupled memory (TCM) for rapid data access during cryptographic operations. The TCM is placed within the coprocessor, ensuring quick retrieval of critical data and optimizing overall performance. Additionally, the program memory is positioned outside the coprocessor, allowing for easy updates and reconfiguration, which enhances adaptability to future algorithm implementations. Direct links are employed instead of DMA(Direct memory access) for data transfer, ensuring faster communication and reducing complexity. The AMBA-based communication architecture facilitates seamless interaction between the coprocessor and the main CPU, streamlining data flow and ensuring efficient utilization of system resources. The abstract nature of the coprocessor allows for easy integration of new cryptographic algorithms in the future. As the security landscape continues to evolve, the coprocessor can adapt and incorporate emerging algorithms, making it a future-proof solution for cryptographic processing. Furthermore, this study explores the addition of custom instructions into RISC-V ISE (Instruction Set Extension) to enhance cryptographic operations. By incorporating custom instructions specifically tailored for cryptographic algorithms, the coprocessor achieves higher efficiency and reduced cycles per instruction (CPI) compared to traditional instruction sets. The adoption of RISC-V 128-bit architecture significantly reduces the total number of instructions required for complex cryptographic tasks, leading to faster execution times and improved overall performance. Comparisons are made with 32-bit and 64-bit architectures, highlighting the advantages of the 128-bit architecture in terms of reduced instruction count and CPI. In conclusion, the abstract cryptographic coprocessor presented in this study offers significant advantages in terms of algorithm flexibility, security, and integration with the main CPU. By leveraging AMBA protocols and employing direct links for data transfer, the coprocessor achieves high-performance cryptographic operations without compromising system efficiency. With its TCM and external program memory, the coprocessor is capable of securely executing a wide range of cryptographic algorithms. This versatility and adaptability, coupled with the benefits of custom instructions and the 128-bit architecture, make it an invaluable asset for secure embedded systems, meeting the demands of modern cryptographic applications.

Keywords: abstract cryptographic coprocessor, AMBA protocols, ECC, RSA, AES, tightly coupled memory, secure embedded systems, RISC-V ISE, custom instructions, instruction count, cycles per instruction

Procedia PDF Downloads 62

Authors: Vanja Vlajkov, Ivana PajčIn, Mila Grahovac, Marta Loc, Dragana Budakov, Jovana Grahovac

Abstract:

The rhizosphere soil refers to the plant roots' dynamic environment characterized by their inhabitants' high biological activity. Rhizospheric bacteria are recognized as effective biocontrol agents and considered cardinal in alternative strategies for securing ecological plant diseases management. The need to suppress fungal pathogens is an urgent task, not only because of the direct economic losses caused by infection but also due to their ability to produce mycotoxins with harmful effects on human health. Aspergillus and Fusarium species are well-known producers of toxigenic metabolites with a high capacity to colonize crops and enter the food chain. The bacteria belonging to the Bacillus genus has been conceded as a plant beneficial species in agricultural practice and identified as plant growth-promoting rhizobacteria (PGPR). Besides incontestable potential, the full commercialization of microbial biopesticides is in the preliminary phase. Thus, there is a constant need for estimating the suitability of novel strains to be used as a central point of viable bioprocess leading to market-ready product development. In the present study, 76 potential producing strains were isolated from the rhizosphere soil, sampled from different localities in the Autonomous Province of Vojvodina, Republic of Serbia. The selective isolation process of strains started by resuspending 1 g of soil samples in 9 ml of saline and incubating at 28° C for 15 minutes at 150 rpm. After homogenization, thermal treatment at 100° C for 7 minutes was performed. Dilution series (10-1-10-3) were prepared, and 500 µl of each was inoculated on nutrient agar plates and incubated at 28° C for 48 h. The pure cultures of morphologically different strains indicating belonging to the Bacillus genus were obtained by the spread-plate technique. The cultivation of the isolated strains was carried out in an Erlenmeyer flask for 96 h, at 28 °C, 170 rpm. The antagonistic activity screening included two phytopathogenic fungi as test microorganisms: Aspergillus sp. and Fusarium sp. The mycelial growth inhibition was estimated based on the antimicrobial activity testing of cultivation broth by the diffusion method. For the Aspergillus sp., the highest antifungal activity was recorded for the isolates Kro-4a and Mah-1a. In contrast, for the Fusarium sp., following 15 isolates exhibited the highest antagonistic effect Par-1, Par-2, Par-3, Par-4, Kup-4, Paš-1b, Pap-3, Kro-2, Kro-3a, Kro-3b, Kra-1a, Kra-1b, Šar-1, Šar-2b and Šar-4. One-way ANOVA was performed to determine the antagonists' effect statistical significance on inhibition zone diameter. Duncan's multiple range test was conducted to define homogenous groups of antagonists with the same level of statistical significance regarding their effect on antimicrobial activity of the tested cultivation broth against tested pathogens. The study results have pointed out the significant in vitro potential of the isolated strains to be used as biocontrol agents for the suppression of the tested mycotoxigenic fungi. Further research should include the identification and detailed characterization of the most promising isolates and mode of action of the selected strains as biocontrol agents. The following research should also involve bioprocess optimization steps to fully reach the selected strains' potential as microbial biopesticides and design cost-effective biotechnological production.

Keywords: Bacillus, biocontrol, bioprocess, mycotoxigenic fungi

Procedia PDF Downloads 189

Authors: Trenten Theis, Trevor Daubert, Kennedy Kluthe, Austin Nuxoll

Abstract:

Staphylococcus aureus is a gram-positive bacterium responsible for an estimated 23,000 deaths in the United States and 25,000 deaths in the European Union annually. Recurring S. aureus bacteremia is associated with biofilm-mediated infections and can occur in 5 - 20% of cases, even with the use of antibiotics. Despite these infections being caused by drug-susceptible pathogens, they are surprisingly difficult to eradicate. One potential explanation for this is the presence of persister cells—a dormant type of cell that shows a high tolerance to antibiotic treatment. Recent studies have shown a connection between low intracellular ATP and persister cell formation. Specifically, this decrease in ATP, and therefore increase in persister cell formation, is due to an interrupted tricarboxylic acid (TCA) cycle. However, S. aureus persister cells’ role in pathogenesis remains unclear. Initial studies have shown that a fumC (TCA cycle gene) knockout survives challenge from aspects of the innate immune system better than wild-type S. aureus. Specifically, challenges from two antimicrobial peptides--LL-37 and hBD-3—show a log increase in survival of the fumC::N∑ strain compared to wild type S. aureus after 18 hours. Furthermore, preliminary studies show that the fumC knockout has a log more survival within a macrophage. These data lead us to hypothesize that the fumC knockout is better suited to other aspects of the innate immune system compared to wild-type S. aureus. To further investigate the mechanism for increased survival of fumC::N∑ within a macrophage, we tested bacterial growth in the presence of reactive oxygen species (ROS), reactive nitrogen species (RNS), and a low pH. Preliminary results suggest that the fumC knockout has increased growth compared to wild-type S. aureus in the presence of all three antimicrobial factors; however, no difference was observed in any single factor alone. To investigate survival within a host, a nine-day biofilm-associated catheter infection was performed on 6–8-week-old male and female C57Bl/6 mice. Although both sexes struggled to clear the infection, female mice were trending toward more frequently clearing the HG003 wild-type infection compared to the fumC::N∑ infection. One possible reason for the inability to reduce the bacterial burden is that biofilms are largely composed of persister cells. To test this hypothesis further, flow cytometry in conjunction with a persister cell marker was used to measure persister cells within a biofilm. Cap5A (a known persister cell marker) expression was found to be increased in a maturing biofilm, with the lowest levels of expression seen in immature biofilms and the highest expression exhibited by the 48-hour biofilm. Additionally, bacterial cells in a biofilm state closely resemble persister cells and exhibit reduced membrane potential compared to cells in planktonic culture, further suggesting biofilms are largely made up of persister cells. These data may provide an explanation as to why infections caused by antibiotic-susceptible strains remain difficult to treat.

Keywords: antibiotic tolerance, Staphylococcus aureus, host-pathogen interactions, microbial pathogenesis

Procedia PDF Downloads 176

Authors: Arifur Rahman, Ardeshir Amirkhani, Honghua Hu, Mark Molloy, Karen Vickery

Abstract:

Introduction and Objectives: Staphylococcus aureus and coagulase-negative staphylococci comprises approximately 65% of infections associated with medical devices and are well known for their biofilm formatting ability. Biofilm-related infections are extremely difficult to eradicate owing to their high tolerance to antibiotics and host immune defences. Currently, there is no efficient method for early biofilm detection. A better understanding to enable detection of biofilm specific proteins in vitro and in vivo can be achieved by studying planktonic and different growth phases of biofilms using a proteome analysis approach. Our goal was to construct a reference map of planktonic and biofilm associated proteins of S. aureus. Methods: S. aureus reference strain (ATCC 25923) was used to grow 24 hours planktonic, 3-day wet biofilm (3DWB), and 12-day wet biofilm (12DWB). Bacteria were grown in tryptic soy broth (TSB) liquid medium. Planktonic growth was used late logarithmic bacteria, and the Centres for Disease Control (CDC) biofilm reactor was used to grow 3 days, and 12-day hydrated biofilms, respectively. Samples were subjected to reduction, alkylation and digestion steps prior to Multiplex labelling using Tandem Mass Tag (TMT) 10-plex reagent (Thermo Fisher Scientific). The labelled samples were pooled and fractionated by high pH RP-HPLC which followed by loading of the fractions on a nanoflow UPLC system (Eksigent UPLC system, AB SCIEX). Mass spectrometry (MS) data were collected on an Orbitrap Elite (Thermo Fisher Scientific) Mass Spectrometer. Protein identification and relative quantitation of protein levels were performed using Proteome Discoverer (version 1.3, Thermo Fisher Scientific). After the extraction of protein ratios with Proteome Discoverer, additional processing, and statistical analysis was done using the TMTPrePro R package. Results and Discussion: The present study showed that a considerable proteomic difference exists among planktonic and biofilms from S. aureus. We identified 1636 total extracellular secreted proteins, of which 350 and 137 proteins of 3DWB and 12DWB showed significant abundance variation from planktonic preparation, respectively. Of these, simultaneous up-regulation in between 3DWB and 12DWB proteins such as extracellular matrix-binding protein ebh, enolase, transketolase, triosephosphate isomerase, chaperonin, peptidase, pyruvate kinase, hydrolase, aminotransferase, ribosomal protein, acetyl-CoA acetyltransferase, DNA gyrase subunit A, glycine glycyltransferase and others we found in this biofilm producer. On the contrary, simultaneous down-regulation in between 3DWB and 12DWB proteins such as alpha and delta-hemolysin, lipoteichoic acid synthase, enterotoxin I, serine protease, lipase, clumping factor B, regulatory protein Spx, phosphoglucomutase, and others also we found in this biofilm producer. In addition, we also identified a big percentage of hypothetical proteins including unique proteins. Therefore, a comprehensive knowledge of planktonic and biofilm associated proteins identified by S. aureus will provide a basis for future studies on the development of vaccines and diagnostic biomarkers. Conclusions: In this study, we constructed an initial reference map of planktonic and various growth phase of biofilm associated proteins which might be helpful to diagnose biofilm associated infections.

Keywords: bacterial biofilms, CDC bioreactor, S. aureus, mass spectrometry, TMT

Procedia PDF Downloads 164

Authors: Victor Mantilla, Romeu Vicente, António Figueiredo, Victor Ferreira, Sandra Sorte

Abstract:

Integrating dynamic facades into contemporary building design is shaping a new era of energy efficiency and user comfort. These innovative facades, often constructed using lightweight construction systems and materials, offer an opportunity to have a responsive and adaptive nature to the dynamic behavior of the outdoor climate. Therefore, in regions characterized by high fluctuations in daily temperatures, the ability to adapt to environmental changes is of paramount importance and a challenge. This paper presents a thorough review of the state of the art on double-skin facades (DSF), focusing on lightweight solutions for the external envelope. Dynamic facades featuring elements like movable shading devices, phase change materials, and advanced control systems have revolutionized the built environment. They offer a promising path for reducing energy consumption while enhancing occupant well-being. Lightweight construction systems are increasingly becoming the choice for the constitution of these facade solutions, offering benefits such as reduced structural loads and reduced construction waste, improving overall sustainability. However, the performance of dynamic facades based on low thermal inertia solutions in climatic contexts with high thermal amplitude is still in need of research since their ability to adapt is traduced in variability/manipulation of the thermal transmittance coefficient (U-value). Emerging technologies can enable such a dynamic thermal behavior through innovative materials, changes in geometry and control to optimize the facade performance. These innovations will allow a facade system to respond to shifting outdoor temperature, relative humidity, wind, and solar radiation conditions, ensuring that energy efficiency and occupant comfort are both met/coupled. This review addresses the potential configuration of double-skin facades, particularly concerning their responsiveness to seasonal variations in temperature, with a specific focus on addressing the challenges posed by winter and summer conditions. Notably, the design of a dynamic facade is significantly shaped by several pivotal factors, including the choice of materials, geometric considerations, and the implementation of effective monitoring systems. Within the realm of double skin facades, various configurations are explored, encompassing exhaust air, supply air, and thermal buffering mechanisms. According to the review places a specific emphasis on the thermal dynamics at play, closely examining the impact of factors such as the color of the facade, the slat angle's dimensions, and the positioning and type of shading devices employed in these innovative architectural structures.This paper will synthesize the current research trends in this field, with the presentation of case studies and technological innovations with a comprehensive understanding of the cutting-edge solutions propelling the evolution of building envelopes in the face of climate change, namely focusing on double-skin lightweight solutions to create sustainable, adaptable, and responsive building envelopes. As indicated in the review, flexible and lightweight systems have broad applicability across all building sectors, and there is a growing recognition that retrofitting existing buildings may emerge as the predominant approach.

Keywords: adaptive, control systems, dynamic facades, energy efficiency, responsive, thermal comfort, thermal transmittance

Procedia PDF Downloads 70

Authors: Prajna Paramita Naik, Sujit Kumar Bhutia

Abstract:

Background: Regardless of the development multimodal treatment strategies, oral squamous cell carcinoma (OSCC) is often associated with a high rate of recurrence, metastasis and chemo- and radio- resistance. The present study inspected the relevance of CD44, ABCB1 and ADAM17 expression as a putative stem cell compartment in oral squamous cell carcinoma (OSCC) and deciphered the role of autophagy in regulating the expression of aforementioned proteins, stemness and chemoresistance. Methods: A retrospective analysis of CD44, ABCB1 and ADAM17 expression with respect to the various clinicopathological factors of sixty OSCC patients were determined via immunohistochemistry. The correlation among CD44, ABCB1 and ADAM17 expression was established. Sphere formation assay, flow cytometry and fluorescence microscopy were conducted to elucidate the stemness and chemoresistance nature of established cisplatin-resistant oral cancer cells (FaDu). The pattern of expression of CD44, ABCB1 and ADAM17 in parental (FaDu-P) and resistant FaDu cells (FaDu-CDDP-R) were investigated through fluorescence microscopy. Western blot analysis of autophagy marker proteins was performed to compare the status of autophagy in parental and resistant FaDu cell. To investigate the role of autophagy in chemoresistance and stemness, sphere formation assay, immunofluorescence and Western blot analysis was performed post transfection with siATG14 and the level of expression of autophagic proteins, mitochondrial protein and stemness-associated proteins were analyzed. The statistical analysis was performed by GraphPad Prism 4.0 software. p-value was defined as follows: not significant (n.s.): p > 0.05;*: p ≤ 0.05; **: p ≤ 0.01; ***: p ≤ 0.001; ****: p ≤ 0.0001 were considered statistically significant. Results: In OSCC, high CD44, ABCB1 and ADAM17 expression were significantly correlated with higher tumor grades and poor differentiation. However, the expression of these proteins was not related to the age and sex of OSCC patients. Moreover, the expression of CD44, ABCB1 and ADAM17 were positively correlated with each other. In vitro and OSCC tissue double labeling experiment data showed that CD44+ cells were highly associated with ABCB1 and ADAM17 expression. Further, FaDu-CDDP-R cells showed higher sphere forming capacity along with increased fraction of the CD44+ population and β-catenin expression FaDu-CDDP-R cells also showed accelerated expression of CD44, ABCB1 and ADAM17. A comparatively higher autophagic flux was observed in FaDu-CDDP-R against FaDu-P cells. The expression of mitochondrial proteins was noticeably reduced in resistant cells as compared to parental cells indicating the occurrence of autophagy-mediated mitochondrial degradation in oral cancer. Moreover, inhibition of autophagy was coupled with the decreased formation of orospheres suggesting autophagy-mediated stemness in oral cancer. Blockade of autophagy was also found to induce the restoration of mitochondrial proteins in FaDu-CDDP-R cells indicating the involvement of mitophagy in chemoresistance. Furthermore, a reduced expression of CD44, ABCB1 and ADAM17 was also observed in ATG14 deficient cells FaDu-P and FaDu-CDDP-R cells. Conclusion: The CD44+ ⁄ABCB1+ ⁄ADAM17+ expression in OSCC might be associated with chemoresistance and a putative CSC compartment. Further, the present study highlights the contribution of mitophagy in chemoresistance and confirms the potential involvement of autophagic regulation in acquisition of stem-like characteristics in OSCC.

Keywords: ABCB1, ADAM17, autophagy, CD44, chemoresistance, mitophagy, OSCC, stemness

Procedia PDF Downloads 191

Authors: Meenakshi Barsaul Chauhan, Aastha Chauhan, Shilpa Hurmade, Rajeev Sen, Jyotsna Sen, Monika Dalal

Abstract:

Introduction: Ovarian masses are common forms of neoplasm in women and represent 2/3rd of gynaecological malignancies. A pre-operative suggestion of malignancy can guide the gynecologist to refer women with suspected pelvic mass to a gynecological oncologist for appropriate therapy and optimized treatment, which can improve survival. In the younger age group preoperative differentiation into benign or malignant pathology can decide for conservative or radical surgery. Imaging modalities have a definite role in establishing the diagnosis. By using International Ovarian Tumor Analysis (IOTA) classification with sonography, costly radiological methods like Magnetic Resonance Imaging (MRI) / computed tomography (CT) scan can be reduced, especially in developing countries like India. Thus, this study is being undertaken to evaluate the role of clinical methods and sonography for diagnosis of the nature of the ovarian tumor. Material And Methods: This prospective observational study was conducted on 40 patients presenting with ovarian masses, in the Department of Obstetrics and Gynaecology, at a tertiary care center in northern India. Functional cysts were excluded. Ultrasonography and color Doppler were performed on all the cases.IOTA rules were applied, which take into account locularity, size, presence of solid components, acoustic shadow, dopper flow etc . Magnetic Resonance Imaging (MRI) / computed tomography (CT) scans abdomen and pelvis were done in cases where sonography was inconclusive. In inoperable cases, Fine needle aspiration cytology (FNAC) was done. The histopathology report after surgery and cytology report after FNAC was correlated statistically with the pre-operative diagnosis made clinically and sonographically using IOTA rules. Statistical Analysis: Descriptive measures were analyzed by using mean and standard deviation and the Student t-test was applied and the proportion was analyzed by applying the chi-square test. Inferential measures were analyzed by sensitivity, specificity, negative predictive value, and positive predictive value. Results: Provisional diagnosis of the benign tumor was made in 16(42.5%) and of the malignant tumor was made in 24(57.5%) patients on the basis of clinical findings. With IOTA simple rules on sonography, 15(37.5%) were found to be benign, while 23 (57.5%) were found to be malignant and findings were inconclusive in 2 patients (5%). FNAC/Histopathology reported that benign ovarian tumors were 14 (35%) and 26(65%) were malignant, which was taken as the gold standard. The clinical finding alone was found to have a sensitivity of 66.6% and a specificity of 90.9%. USG alone had a sensitivity of 86% and a specificity of 80%. When clinical findings and IOTA simple rules of sonography were combined (excluding inconclusive masses), the sensitivity and specificity were 83.3% and 92.3%, respectively. While including inconclusive masses, sensitivity came out to be 91.6% and specificity was 89.2. Conclusion: IOTA's simple sonography rules are highly sensitive and specific in the prediction of ovarian malignancy and also easy to use and easily reproducible. Thus, combining clinical examination with USG will help in the better management of patients in terms of time, cost and better prognosis. This will also avoid the need for costlier modalities like CT, and MRI.

Keywords: benign, international ovarian tumor analysis classification, malignant, ovarian tumours, sonography

Procedia PDF Downloads 74

Authors: Miria Gambardella

Abstract:

The influence of solidarity demonstrations towards the Zapatista National Liberation Army has been constantly present over the years, both locally and internationally, guaranteeing visibility to the cause, shaping the movement’s choices, and influencing its hopes of impact worldwide. Most of the coffee produced by the autonomous cooperatives from Chiapas is exported, therefore making coffee trade the main income from international solidarity networks. The question arises about the implications of the relations established between the communities in resistance in Southeastern Mexico and international solidarity movements, specifically on the strategies adopted to conciliate army's demands for autonomy and economic asymmetries between Zapatista cooperatives producing coffee and European collectives who hold purchasing power. In order to deepen the inquiry on those topics, a year-long multi-site investigation was carried out. The first six months of fieldwork were based in Barcelona, where Zapatista coffee was first traded in Spain and where one of the historical and most important European solidarity groups can be found. The last six months of fieldwork were carried out directly in Chiapas, in contact with coffee producers, Zapatista political authorities, international activists as well as vendors, and the rest of the network implicated in coffee production, roasting, and sale. The investigation was based on qualitative research methods, including participatory observation, focus groups, and semi-structured interviews. The analysis did not only focus on retracing the steps of the market chain as if it could be considered a linear and unilateral process, but it rather aimed at exploring actors’ reciprocal perceptions, roles, and dynamics of power. Demonstrations of solidarity and the money circulation they imply aim at changing the system in place and building alternatives, among other things, on the economic level. This work analyzes the formulation of discourse and the organization of solidarity activities that aim at building opportunities for action within a highly politicized economic sphere to which access must be regularly legitimized. The meaning conveyed by coffee is constructed on a symbolic level by the attribution of moral criteria to transactions. The latter participate in the construction of imaginaries that circulate through solidarity movements with the Zapatista rebellion. Commercial exchanges linked to solidarity networks turned out to represent much more than monetary transactions. The social, cultural, and political spheres are invested by ethics, which penetrates all aspects of militant action. It is at this level that the boundaries of different collective actors connect, contaminating each other: merely following the money flow would have been limiting in order to account for a reality within which imaginary is one of the main currencies. The notions of “trust”, “dignity” and “reciprocity” are repeatedly mobilized to negotiate discontinuous and multidirectional flows in the attempt to balance and justify commercial relations in a politicized context that characterizes its own identity through demonizing “market economy” and its dehumanizing powers.

Keywords: coffee trade, economic anthropology, international cooperation, Zapatista National Liberation Army

Procedia PDF Downloads 76

Authors: Alberto Fina, Samuele Colonna, Maria del Mar Bernal, Orietta Monticelli, Mauro Tortello, Renato Gonnelli, Julio Gomez, Chiara Novara, Guido Saracco

Abstract:

Thermally conductive polymer nanocomposites are of high interest for several applications including low-temperature heat recovery, heat exchangers in a corrosive environment and heat management in electronics and flexible electronics. In this paper, the preparation of thermally conductive nanocomposites exploiting graphene-related materials is addressed, along with their thermal characterization. In particular, correlations between 1- chemical and physical features of the nanoflakes and 2- processing conditions with the heat conduction properties of nanocomposites is studied. Polymers are heat insulators; therefore, the inclusion of conductive particles is the typical solution to obtain a sufficient thermal conductivity. In addition to traditional microparticles such as graphite and ceramics, several nanoparticles have been proposed, including carbon nanotubes and graphene, for the use in polymer nanocomposites. Indeed, thermal conductivities for both carbon nanotubes and graphenes were reported in the wide range of about 1500 to 6000 W/mK, despite such property may decrease dramatically as a function of the size, number of layers, the density of topological defects, re-hybridization defects as well as on the presence of impurities. Different synthetic techniques have been developed, including mechanical cleavage of graphite, epitaxial growth on SiC, chemical vapor deposition, and liquid phase exfoliation. However, the industrial scale-up of graphene, defined as an individual, single-atom-thick sheet of hexagonally arranged sp2-bonded carbons still remains very challenging. For large scale bulk applications in polymer nanocomposites, some graphene-related materials such as multilayer graphenes (MLG), reduced graphene oxide (rGO) or graphite nanoplatelets (GNP) are currently the most interesting graphene-based materials. In this paper, different types of graphene-related materials were characterized for their chemical/physical as well as for thermal properties of individual flakes. Two selected rGOs were annealed at 1700°C in vacuum for 1 h to reduce defectiveness of the carbon structure. Thermal conductivity increase of individual GNP with annealing was assessed via scanning thermal microscopy. Graphene nano papers were prepared from both conventional RGO and annealed RGO flakes. Characterization of the nanopapers evidenced a five-fold increase in the thermal diffusivity on the nano paper plane for annealed nanoflakes, compared to pristine ones, demonstrating the importance of structural defectiveness reduction to maximize the heat dissipation performance. Both pristine and annealed RGO were used to prepare polymer nanocomposites, by melt reactive extrusion. Thermal conductivity showed two- to three-fold increase in the thermal conductivity of the nanocomposite was observed for high temperature treated RGO compared to untreated RGO, evidencing the importance of using low defectivity nanoflakes. Furthermore, the study of different processing paremeters (time, temperature, shear rate) during the preparation of poly (butylene terephthalate) nanocomposites evidenced a clear correlation with the dispersion and fragmentation of the GNP nanoflakes; which in turn affected the thermal conductivity performance. Thermal conductivity of about 1.7 W/mK, i.e. one order of magnitude higher than for pristine polymer, was obtained with 10%wt of annealed GNPs, which is in line with state of the art nanocomposites prepared by more complex and less upscalable in situ polymerization processes.

Keywords: graphene, graphene-related materials, scanning thermal microscopy, thermally conductive polymer nanocomposites

Procedia PDF Downloads 259

Authors: Walter E. Allen, Robert D. Murray

Abstract:

Many large transit agencies have adopted RFID technology and electronic automatic fare collection (AFC) or smart card systems, but small and rural agencies remain tied to obsolete manual, cash-based fare collection. Small countries or transit agencies can benefit from the implementation of smart card AFC technology with the promise of increased passenger convenience, added passenger satisfaction and improved agency efficiency. For transit agencies, it reduces revenue loss, improves passenger flow and bus stop data. For countries, further implementation into security, distribution of social services or currency transactions can provide greater benefits. However, small countries or transit agencies cannot afford expensive proprietary smart card solutions typically offered by the major system suppliers. Deployment of Contactless Fare Media System (CFMS) Standard eliminates the proprietary solution, ultimately lowering the cost of implementation. Acumen Building Enterprise, Inc. chose the Yuma County Intergovernmental Public Transportation Authority (YCIPTA) existing proprietary YCAT smart card system to implement CFMS. The revised system enables the purchase of fare product online with prepaid debit or credit cards using the Payment Gateway Processor. Open and interoperable smart card standards for transit have been developed. During the 90-day Pilot Operation conducted, the transit agency gathered the data from the bus AcuFare 200 Card Reader, loads (copies) the data to a USB Thumb Drive and uploads the data to the Acumen Host Processing Center for consolidation of the data into the transit agency master data file. The transition from the existing proprietary smart card data format to the new CFMS smart card data format was transparent to the transit agency cardholders. It was proven that open standards and interoperability design can work and reduce both implementation and operational costs for small transit agencies or countries looking to expand smart card technology. Acumen was able to avoid the implementation of the Payment Card Industry (PCI) Data Security Standards (DSS) which is expensive to develop and costly to operate on a continuing basis. Due to the substantial additional complexities of implementation and the variety of options presented to the transit agency cardholder, Acumen chose to implement only the Directed Autoload. To improve the implementation efficiency and the results for a similar undertaking, it should be considered that some passengers lack credit cards and are averse to technology. There are more than 1,300 small and rural agencies in the United States. This grows by 10 fold when considering small countries or rural locations throughout Latin American and the world. Acumen is evaluating additional countries, sites or transit agency that can benefit from the smart card systems. Frequently, payment card systems require extensive security procedures for implementation. The Project demonstrated the ability to purchase fare value, rides and passes with credit cards on the internet at a reasonable cost without highly complex security requirements.

Keywords: automatic fare collection, near field communication, small transit agencies, smart cards

Procedia PDF Downloads 274

Authors: Chandranath Chatterjee, Amina Khatun, Bhabagrahi Sahoo

Abstract:

With the changing climate, precipitation events are intensified in the tropical river basins. Since these river basins are significantly influenced by the monsoonal rainfall pattern, critical impacts are observed on the agricultural practices in the downstream river reaches. This study analyses the crop damage and associated flood risk in terms of net benefit in the paddy-dominated tropical Indian delta of the Mahanadi River. The Mahanadi River basin lies in eastern part of the Indian sub-continent and is greatly affected by the southwest monsoon rainfall extending from the month of June to September. This river delta is highly flood-prone and has suffered from recurring high floods, especially after the 2000s. In this study, the lumped conceptual model, Nedbør Afstrømnings Model (NAM) from the suite of MIKE models, is used for rainfall-runoff modeling. The NAM model is laterally integrated with the MIKE11-Hydrodynamic (HD) model to route the runoffs up to the head of the delta region. To obtain the precipitation-derived future projected discharges at the head of the delta, nine Global Climate Models (GCMs), namely, BCC-CSM1.1(m), GFDL-CM3, GFDL-ESM2G, HadGEM2-AO, IPSL-CM5A-LR, IPSL-CM5A-MR, MIROC5, MIROC-ESM-CHEM and NorESM1-M, available in the Coupled Model Intercomparison Project-Phase 5 (CMIP5) archive are considered. These nine GCMs are previously found to best-capture the Indian Summer Monsoon rainfall. Based on the performance of the nine GCMs in reproducing the historical discharge pattern, three GCMs (HadGEM2-AO, IPSL-CM5A-MR and MIROC-ESM-CHEM) are selected. A higher Taylor Skill Score is considered as the GCM selection criteria. Thereafter, the 10-year return period design flood is estimated using L-moments based flood frequency analysis for the historical and three future projected periods (2010-2039, 2040-2069 and 2070-2099) under Representative Concentration Pathways (RCP) 4.5 and 8.5. A non-dimensional hydrograph analysis is performed to obtain the hydrographs for the historical/projected 10-year return period design floods. These hydrographs are forced into the calibrated and validated coupled 1D-2D hydrodynamic model, MIKE FLOOD, to simulate the flood inundation in the delta region. Historical and projected flood risk is defined based on the information about the flood inundation simulated by the MIKE FLOOD model and the inundation depth-damage-duration relationship of a normal rice variety cultivated in the river delta. In general, flood risk is expected to increase in all the future projected time periods as compared to the historical episode. Further, in comparison to the 2010s (2010-2039), an increased flood risk in the 2040s (2040-2069) is shown by all the three selected GCMs. However, the flood risk then declines in the 2070s as we move towards the end of the century (2070-2099). The methodology adopted herein for flood risk assessment is one of its kind and may be implemented in any world-river basin. The results obtained from this study can help in future flood preparedness by implementing suitable flood adaptation strategies.

Keywords: flood frequency analysis, flood risk, global climate models (GCMs), paddy cultivation

Procedia PDF Downloads 64

Authors: Babak Forouraghi

Abstract:

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

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

Procedia PDF Downloads 52

Authors: Carmen García Sánchez

Abstract:

The UN's 17 Sustainable Development Goals – specifically the nº 3 and nº 11- urgently call for new architectural design solutions at different design scales to increase human contact with nature in the health and wellbeing promotion of primarily urban communities. The discipline of Interior Design offers an important alternative to large-scale nature-inclusive actions which are not always possible due to space limitations. These circumstances provide an immense opportunity to integrate biophilic design, a complex emerging and under-developed approach that pursues sustainable design strategies for increasing the human-nature connection through the experience of the built environment. Biophilic design explores the diverse ways humans are inherently inclined to affiliate with nature, attach meaning to and derive benefit from the natural world. It represents a biological understanding of architecture which categorization is still in progress. The internationally renowned Danish domestic architecture built in the 1950´s and early 1960´s - a golden age of Danish modern architecture - left a leading legacy that has greatly influenced the domestic sphere and has further led the world in terms of good design and welfare. This study examines how four existing post-war domestic buildings establish a dialogue with nature and her variations over time. The case-studies unveil both memorable and unique biophilic resources through sophisticated and original design expressions, where transformative processes connect the users to the natural setting and reflect fundamental ways in which they attach meaning to the place. In addition, fascinating analogies in terms of this nature interaction with particular traditional Japanese architecture inform the research. They embody prevailing lessons for our time today. The research methodology is based on a thorough literature review combined with a phenomenological analysis into how these case-studies contribute to the connection between humans and nature, after conducting fieldwork throughout varying seasons to document understanding in nature transformations multi-sensory perception (via sight, touch, sound, smell, time and movement) as a core research strategy. The cases´ most outstanding features have been studied attending the following key parameters: 1. Space: 1.1. Relationships (itineraries); 1.2. Measures/scale; 2. Context: Context: Landscape reading in different weather/seasonal conditions; 3. Tectonic: 3.1. Constructive joints, elements assembly; 3.2. Structural order; 4. Materiality: 4.1. Finishes, 4.2. Colors; 4.3. Tactile qualities; 5. Daylight interplay. Departing from an artistic-scientific exploration this groundbreaking study provides sustainable practical design strategies, perspectives, and inspiration to boost humans´ contact with nature through the experience of the interior built environment. Some strategies are associated with access to outdoor space or require ample space, while others can thrive in a dense urban context without direct access to the natural environment. The objective is not only to produce knowledge, but to phase in biophilic design in the built environment, expanding its theory and practice into a new dimension. Its long-term vision is to efficiently enhance the health and well-being of urban communities through daily interaction with Nature.

Keywords: sustainability, biophilic design, architectural design, interior design, nature, Danish architecture, Japanese architecture

Procedia PDF Downloads 87

Authors: Yuguang Gao, Mingtao Deng

Abstract:

The integration of independently operating hospitals into a unified healthcare service system has become a strategic imperative in the pursuit of hospitals’ high-quality development. Central to the concept of group governance over such transformation, exemplified by a collaborative medical alliance, is the delineation of shared value, vision, and goals. Given the inherent disparity in capabilities among hospitals within the alliance, particularly in the treatment of different diseases characterized by Disease Related Groups (DRG) in terms of effectiveness, efficiency and resource utilization, this study aims to address the centralized decision-making of intra-hospital patient referral within the medical alliance to enhance the overall production and quality of service provided. We first introduce the notion of production utility, where a higher production utility for a hospital implies better performance in treating patients diagnosed with that specific DRG group of diseases. Then, a Discrete-Event Simulation (DES) framework is established for patient referral among hospitals, where patient flow modeling incorporates a queueing system with fixed capacities for each hospital. The simulation study begins with a two-member alliance. The pivotal strategy examined is a "whether-to-refer" decision triggered when the bed usage rate surpasses a predefined threshold for either hospital. Then, the decision encompasses referring patients to the other hospital based on DRG groups’ production utility differentials as well as bed availability. The objective is to maximize the total production utility of the alliance while minimizing patients’ average length of stay and turnover rate. Thus the parameter under scrutiny is the bed usage rate threshold, influencing the efficacy of the referral strategy. Extending the study to a three-member alliance, which could readily be generalized to multi-member alliances, we maintain the core setup while introducing an additional “which-to-refer" decision that involves referring patients with specific DRG groups to the member hospital according to their respective production utility rankings. The overarching goal remains consistent, for which the bed usage rate threshold is once again a focal point for analysis. For the two-member alliance scenario, our simulation results indicate that the optimal bed usage rate threshold hinges on the discrepancy in the number of beds between member hospitals, the distribution of DRG groups among incoming patients, and variations in production utilities across hospitals. Transitioning to the three-member alliance, we observe similar dependencies on these parameters. Additionally, it becomes evident that an imbalanced distribution of DRG diagnoses and further disparity in production utilities among member hospitals may lead to an increase in the turnover rate. In general, it was found that the intra-hospital referral mechanism enhances the overall production utility of the medical alliance compared to individual hospitals without partnership. Patients’ average length of stay is also reduced, showcasing the positive impact of the collaborative approach. However, the turnover rate exhibits variability based on parameter setups, particularly when patients are redirected within the alliance. In conclusion, the re-structuring of diagnostic disease groups within the medical alliance proves instrumental in improving overall healthcare service outcomes, providing a compelling rationale for the government's promotion of patient referrals within collaborative medical alliances.

Keywords: collaborative medical alliance, disease related group, patient referral, simulation

Procedia PDF Downloads 48