Search results for: vitality and viability

Authors: Iris Xiaohong Quan, Sharon Qi, Kelly Tianqin Shi

Abstract:

This study focuses on the critical role of insurance policies in a world grappling with increasing mental health challenges, as they significantly influence the dynamics of healthcare businesses and entrepreneurial ventures. The paper utilizes the mental health sector as a case to examine the impact of insurance policies on healthcare service providers, entrepreneurs, and individuals seeking mental health support. This paper addressed the following research questions: To what extent do changes in insurance reimbursement policies affect the accessibility and affordability of mental health services for patients, and how does this impact the overall demand for such services? What are the barriers and opportunities that mental health entrepreneurs face and what strategies and adaptations do mental health businesses employ when navigating the evolving landscape of insurance reimbursement policies? How do changes in insurance reimbursement policies, specifically related to mental health services, influence the financial viability and sustainability of mental health clinics and private practices? Employing a self-designed survey aimed at autism spectrum disorder (ASD) treatment companies, alongside two in-depth case studies and an analysis of pertinent insurance policies and documents, this research aims to elucidate the multifaceted influence of insurance policies on the mental health industry. The findings from this study reveal how insurance policies shape the landscape of mental health businesses and their operations. A total of 821 autism treatment organizations or offices were contacted by telephone between November 1, 2019, and January 31, 2020. About half of the offices (53.33%) were established in the past five years, and 80% were established in the past 15 years. There is a significant increase in the establishment of ABA service centers in the recent two decades as a result of autism insurance reform, the increasing social awareness of ASD, and the redefinition of autism. In addition, almost half of the ABA service providers we surveyed had a patient size ranging from 20 to 50 in the year when the residence state passed the legislation for autism insurance coverage. On average, an ABA service provider works with 5.3 insurance companies. This research find that insurance is the main source of revenue for most ABA service providers. However, our survey reveals that clients’ out of pocket payment has been the second main revenue sources. Despite the changes of regulations and insurance policies in all states, clients still have to pay a fraction of, if not all, the ABA treatment service fees out of pocket. This research shows that some ABA service providers seek federal and government funds and grants to support their services and businesses. Our further analysis with the in-depth case studies and other secondary data also indicate the rise of entrepreneurial startups in the mental health industry. Overall, this research sheds light on both the challenges and opportunities presented by insurance policies in the mental health sector, offering insights into the new industry landscape.

Keywords: entrepreneurship, healthcare policy, insurance policy, mental health industry

Procedia PDF Downloads 39

Authors: Susan Hall, Gary D. Grant, Catherine McDermott, Devinder Arora

Abstract:

Introduction /Aim: The kynurenine pathway is thought to play an important role in the pathophysiology of numerous neurodegenerative diseases including depression, Alzheimer’s disease, and Parkinson’s disease. Numerous neuroactive compounds, including the neurotoxic 3-hydroxyanthranilic acid, 3-hydroxykynurenine and quinolinic acid and the neuroprotective kynurenic acid and picolinic acid, are produced through the metabolism of kynurenine and are thought to be the causative agents responsible for neurodegeneration. The toxicity of 3-hydroxykynurenine, 3-hydroxyanthranilic acid and quinolinic acid has been widely evaluated and demonstrated in primary cell cultures but to date only 3-hydroxykynurenine and 3-hydroxyanthranilic acid have been shown to cause toxicity in immortal tumour cells. The aim of this study was to evaluate the toxicity of kynurenine metabolites, both individually and in combination, on SH-SY5Y neuroblastoma cells after 24 and 72 h exposure in order to explore a cost-effective model to study their neurotoxic effects and potential protective agents. Methods: SH-SY5Y neuroblastoma cells were exposed to various concentrations of the neuroactive kynurenine metabolites, both individually and in combination, for 24 and 72 h, and viability was subsequently evaluated using the Resazurin (Alamar blue) proliferation assay. Furthermore, the effects of these compounds, alone and in combination, on specific death pathways including apoptosis, necrosis and free radical production was evaluated using various assays. Results: Consistent with literature, toxicity was shown with short-term 24-hour treatments at 1000 μM concentrations for both 3-hydroxykynurenine and 3-hydroxyanthranilic acid. Combinations of kynurenine metabolites showed modest toxicity towards SH-SY5Y neuroblastoma cells in a concentration-dependent manner. Specific cell death pathways, including apoptosis, necrosis and free radical production were shown to be increased after both 24 and 72 h exposure of SH-SY5Y neuroblastoma cells to 3-hydroxykynurenine and 3-hydroxyanthranilic acid and various combinations of neurotoxic kynurenine metabolites. Conclusion: It is well documented that neurotoxic kynurenine metabolites show toxicity towards primary human neurons in the nanomolar to low micromolar concentration range. Results show that the concentrations required to show significant cell death are in the range of 1000 µM for 3-hydroxykynurenine and 3-hydroxyanthranilic acid and toxicity of quinolinic acid towards SH-SY5Y was unable to be shown. This differs significantly from toxicities observed in primary human neurons. Combinations of the neurotoxic metabolites were shown to have modest toxicity towards these cells with increased toxicity and activation of cell death pathways observed after 72 h exposure. This study suggests that the 24 h model is unsuitable for use in neurotoxicity studies, however, the 72 h model better represents the observations of the studies using primary human neurons and may provide some benefit in providing a cost-effective model to assess possible protective agents against kynurenine metabolite toxicities.

Keywords: kynurenine metabolites, neurotoxicity, quinolinic acid, SH-SY5Y neuroblastoma

Procedia PDF Downloads 397

Authors: Lydia Tan, Philippe Lemey, Lieselot Houspie, Marco Viveen, Darren Martin, Frank Coenjaerts

Abstract:

Introduction: Human respiratory syncytial virus (hRSV) is the leading cause of severe respiratory tract infections in infants under the age of two. Genomic substitutions and related evolutionary dynamics of hRSV are of great influence on virus transmission behavior. The evolutionary patterns formed are due to a precarious interplay between the host immune response and RSV, thereby selecting the most viable and less immunogenic strains. Studying genomic profiles can teach us which genes and consequent proteins play an important role in RSV survival and transmission dynamics. Study design: In this study, genetic diversity and evolutionary rate analysis were conducted on 36 RSV subgroup B whole genome sequences and 37 subgroup A genome sequences. Clinical RSV isolates were obtained from nasopharyngeal aspirates and swabs of children between 2 weeks and 5 years old of age. These strains, collected during epidemic seasons from 2001 to 2011 in the Netherlands and Belgium by either conventional or 454-sequencing. Sequences were analyzed for genetic diversity, recombination events, synonymous/non-synonymous substitution ratios, epistasis, and translational consequences of mutations were mapped to known 3D protein structures. We used Bayesian statistical inference to estimate the rate of RSV genome evolution and the rate of variability across the genome. Results: The A and B profiles were described in detail and compared to each other. Overall, the majority of the whole RSV genome is highly conserved among all strains. The attachment protein G was the most variable protein and its gene had, similar to the non-coding regions in RSV, more elevated (two-fold) substitution rates than other genes. In addition, the G gene has been identified as the major target for diversifying selection. Overall, less gene and protein variability was found within RSV-B compared to RSV-A and most protein variation between the subgroups was found in the F, G, SH and M2-2 proteins. For the F protein mutations and correlated amino acid changes are largely located in the F2 ligand-binding domain. The small hydrophobic phosphoprotein and nucleoprotein are the most conserved proteins. The evolutionary rates were similar in both subgroups (A: 6.47E-04, B: 7.76E-04 substitution/site/yr), but estimates of the time to the most recent common ancestor were much lower for RSV-B (B: 19, A: 46.8 yrs), indicating that there is more turnover in this subgroup. Conclusion: This study provides a detailed description of whole RSV genome mutations, the effect on translation products and the first estimate of the RSV genome evolution tempo. The immunogenic G protein seems to require high substitution rates in order to select less immunogenic strains and other conserved proteins are most likely essential to preserve RSV viability. The resulting G gene variability makes its protein a less interesting target for RSV intervention methods. The more conserved RSV F protein with less antigenic epitope shedding is, therefore, more suitable for developing therapeutic strategies or vaccines.

Keywords: drug target selection, epidemiology, respiratory syncytial virus, RSV

Procedia PDF Downloads 384

Authors: Fengjuan Wang, Azilawati Jamaludin

Abstract:

Developmental Dyscalculia (DD) is defined as a particular learning difficulty with continuous challenges in learning requisite math skills that cannot be explained by intellectual disability or educational deprivation. Recent studies have increasingly recognized that DD is a heterogeneous, instead of monolithic, learning disorder with not only cognitive and behavioral deficits but so too neural dysfunction. In recent years, neuroimaging studies employed group comparison to explore the neural underpinnings of DD, which contradicted the heterogenous nature of DD and may obfuscate critical individual differences. This research aimed to investigate the neural heterogeneity of DD using case studies with functional near-infrared spectroscopy (fNIRS). A total of 54 aged 6-7 years old of children participated in this study, comprising two comprehensive cognitive assessments, an 8-minute resting state, and an 8-minute one-digit addition task. Nine children met the criteria of DD and scored at or below 85 (i.e., the 16th percentile) on the Mathematics or Math Fluency subtest of the Wechsler Individual Achievement Test, Third Edition (WIAT-III) (both subtest scores were 90 and below). The remaining 45 children formed the typically developing (TD) group. Resting-state data and brain activation in the inferior frontal gyrus (IFG), superior frontal gyrus (SFG), and intraparietal sulcus (IPS) were collected for comparison between each case and the TD group. Graph theory was used to analyze the brain network under the resting state. This theory represents the brain network as a set of nodes--brain regions—and edges—pairwise interactions across areas to reveal the architectural organizations of the nervous network. Next, a single-case methodology developed by Crawford et al. in 2010 was used to compare each case’s brain network indicators and brain activation against 45 TD children’s average data. Results showed that three out of the nine DD children displayed significant deviation from TD children’s brain indicators. Case 1 had inefficient nodal network properties. Case 2 showed inefficient brain network properties and weaker activation in the IFG and IPS areas. Case 3 displayed inefficient brain network properties with no differences in activation patterns. As a rise above, the present study was able to distill differences in architectural organizations and brain activation of DD vis-à-vis TD children using fNIRS and single-case methodology. Although DD is regarded as a heterogeneous learning difficulty, it is noted that all three cases showed lower nodal efficiency in the brain network, which may be one of the neural sources of DD. Importantly, although the current “brain norm” established for the 45 children is tentative, the results from this study provide insights not only for future work in “developmental brain norm” with reliable brain indicators but so too the viability of single-case methodology, which could be used to detect differential brain indicators of DD children for early detection and interventions.

Keywords: brain activation, brain network, case study, developmental dyscalculia, functional near-infrared spectroscopy, graph theory, neural heterogeneity

Procedia PDF Downloads 36

Authors: Hamadi Cherif, Christophe Coquelet, Paolo Stringari, Denis Clodic, Laura Pellegrini, Stefania Moioli, Stefano Langè

Abstract:

Biogas is a promising technology which can be used as a vehicle fuel, for heat and electricity production, or injected in the national gas grid. It is storable, transportable, not intermittent and substitutable for fossil fuels. This gas produced from the wastewater treatment by degradation of organic matter under anaerobic conditions is mainly composed of methane and carbon dioxide. To be used as a renewable fuel, biogas, whose energy comes only from methane, must be purified from carbon dioxide and other impurities such as water vapor, siloxanes and hydrogen sulfide. Purification of biogas for this application particularly requires the removal of hydrogen sulfide, which negatively affects the operation and viability of equipment especially pumps, heat exchangers and pipes, causing their corrosion. Several methods are available to eliminate hydrogen sulfide from biogas. Herein, reactive absorption in structured packed column by means of chemical absorption in aqueous sodium hydroxide solutions is considered. This study is based on simulations using Aspen Plus™ V8.0, and comparisons are done with data from an industrial pilot plant treating 85 Nm3/h of biogas which contains about 30 ppm of hydrogen sulfide. The rate-based model approach has been used for simulations in order to determine the efficiencies of separation for different operating conditions. To describe vapor-liquid equilibrium, a γ/ϕ approach has been considered: the Electrolyte NRTL model has been adopted to represent non-idealities in the liquid phase, while the Redlich-Kwong equation of state has been used for the vapor phase. In order to validate the thermodynamic model, Henry’s law constants of each compound in water have been verified against experimental data. Default values available in Aspen Plus™ V8.0 for the properties of pure components properties as heat capacity, density, viscosity and surface tension have also been verified. The obtained results for physical and chemical properties are in a good agreement with experimental data. Reactions involved in the process have been studied rigorously. Equilibrium constants for equilibrium reactions and the reaction rate constant for the kinetically controlled reaction between carbon dioxide and the hydroxide ion have been checked. Results of simulations of the pilot plant purification section show the influence of low temperatures, concentration of sodium hydroxide and hydrodynamic parameters on the selective absorption of hydrogen sulfide. These results show an acceptable degree of accuracy when compared with the experimental data obtained from the pilot plant. Results show also the great efficiency of sodium hydroxide for the removal of hydrogen sulfide. The content of this compound in the gas leaving the column is under 1 ppm.

Keywords: biogas, hydrogen sulfide, reactive absorption, sodium hydroxide, structured packed column

Procedia PDF Downloads 319

Authors: Thomas Rockstuhl, Soon Ang, Kok Yee Ng, Linn Van Dyne

Abstract:

Intercultural interactions are often challenging and fraught with conflicts. To shed light on how to interact effectively across cultures, academics and practitioners alike have advanced a plethora of intercultural competence models. However, the majority of this work has emphasized distal outcomes, such as job performance and cultural adjustment, rather than proximal outcomes, such as how individuals resolve inevitable intercultural conflicts. As a consequence, the processes by which individuals negotiate challenging intercultural conflicts are not well understood. The current study advances theorizing on intercultural conflict resolution by exploring antecedents of how people resolve intercultural conflicts. To this end, we examine creativity – the generation of novel and useful ideas – in the context of resolving cultural conflicts in intercultural interactions. Based on the dual-identity theory of creativity, we propose that individuals with greater international experience will display greater creativity and that the relationship is accentuated by individual’s cultural intelligence. Two studies test these hypotheses. The first study comprises 84 senior university students, drawn from an international organizational behavior course. The second study replicates findings from the first study in a sample of 89 executives from eleven countries. Participants in both studies provided protocols of their strategies for resolving two intercultural conflicts, as depicted in two multimedia-vignettes of challenging intercultural work-related interactions. Two research assistants, trained in intercultural management but blind to the study hypotheses, coded all strategies for their novelty and usefulness following scoring procedures for creativity tasks. Participants also completed online surveys of demographic background information, including their international experience, and cultural intelligence. Hierarchical linear modeling showed that surprisingly, while international experience is positively associated with usefulness, it is unrelated to novelty. Further, a person’s cultural intelligence strengthens the positive effect of international experience on usefulness and mitigates the effect of international experience on novelty. Theoretically, our findings offer an important theoretical extension to the dual-identity theory of creativity by identifying cultural intelligence as an important individual difference moderator that qualifies the relationship between international experience and creative conflict resolution. In terms of novelty, individuals higher in cultural intelligence seem less susceptible to rigidity effects of international experiences. Perhaps they are more capable of assessing which aspects of culture are relevant and apply relevant experiences when they brainstorm novel ideas. For utility, individuals high in cultural intelligence are better able to leverage on their international experience to assess the viability of their ideas because their richer and more organized cultural knowledge structure allows them to assess possible options more efficiently and accurately. In sum, our findings suggest that cultural intelligence is an important and promising intercultural competence that fosters creative resolutions to intercultural conflicts. We hope that our findings stimulate future research on creativity and conflict resolution in intercultural contexts.

Keywords: cultural Intelligence, intercultural conflict, intercultural creativity, international experience

Procedia PDF Downloads 132

Authors: Marisa Rio, Sharanya Bola, Richard H. W. Funk, Gerald Gerlach

Abstract:

Cell migration, wound healing and regeneration are some of the physiological phenomena in which electric fields (EFs) have proven to have an important function. Physiologically, cells experience electrical signals in the form of transmembrane potentials, ion fluxes through protein channels as well as electric fields at their surface. As soon as a wound is created, the disruption of the epithelial layers generates an electric field of ca. 40-200 mV/mm, directing cell migration towards the wound site, starting the healing process. In vitro electrotaxis, experiments have shown cells respond to DC EFs polarizing and migrating towards one of the poles (cathode or anode). A standard electrotaxis experiment consists of an electrotaxis chamber where cells are cultured, a DC power source and agar salt bridges that help delaying toxic products from the electrodes to attain the cell surface. The electric field strengths used in such an experiment are uniform and homogeneous. In contrast, the endogenous electric field strength around a wound tend to be multi-field and non-homogeneous. In this study, we present a custom device that enables electrotaxis experiments in non-homogeneous DC electric fields. Its main feature involves the replacement of conventional metallic electrodes, separated from the electrotaxis channel by agarose gel bridges, through electrolyte-filled microchannels. The connection to the DC source is made by Ag/AgCl electrodes, incased in agarose gel and placed at the end of each microfluidic channel. An SU-8 membrane closes the fluidic channels and simultaneously serves as the single connection from each of them to the central electrotaxis chamber. The electric field distribution and current density were numerically simulated with the steady-state electric conduction module from ANSYS 16.0. Simulation data confirms the application of nonhomogeneous EF of physiological strength. To validate the biocompatibility of the device cellular viability of the photoreceptor-derived 661W cell line was accessed. The cells have not shown any signs of apoptosis, damage or detachment during stimulation. Furthermore, immunofluorescence staining, namely by vinculin and actin labelling, allowed the assessment of adhesion efficiency and orientation of the cytoskeleton, respectively. Cellular motility in the presence and absence of applied DC EFs was verified. The movement of individual cells was tracked for the duration of the experiments, confirming the EF-induced, cathodal-directed motility of the studied cell line. The in vitro monolayer wound assay, or “scratch assay” is a standard protocol to quantitatively access cell migration in vitro. It encompasses the growth of a confluent cell monolayer followed by the mechanic creation of a scratch, representing a wound. Hence, wound dynamics was monitored over time and compared for control and applied the electric field to quantify cellular population motility.

Keywords: DC non-homogeneous electric fields, electrotaxis, microfluidic biochip, wound healing

Procedia PDF Downloads 249

Authors: Rodrigo Calili, Anna Carolina Sermarini, João Henrique Azevedo, Vanessa Cardoso de Albuquerque, Felipe Gonçalves, Gilberto Jannuzzi

Abstract:

The diffusion of Distributed Energy Resources (DER) has caused structural changes in the relationship between consumers and electrical systems. The Photovoltaic Distributed Generation (PVDG), in particular, is an essential strategy for achieving the 2030 Agenda goals, especially SDG 7 and SDG 13. However, it is observed that most projects involving this technology in Brazil are restricted to the wealthiest classes of society, not yet reaching the low-income population, aligned with theories of energy justice. Considering the research for energy equality, one of the policies adopted by governments is the social electricity tariff (SET), which provides discounts on energy tariffs/bills. However, just granting this benefit may not be effective, and it is possible to merge it with DER technologies, such as the PVDG. Thus, this work aims to evaluate the economic viability of the policy to replace the social electricity tariff (the current policy aimed at the low-income population in Brazil) by PVDG projects. To this end, a proprietary methodology was developed that included: mapping the stakeholders, identifying critical variables, simulating policy options, and carrying out an analysis in the Brazilian context. The simulation answered two key questions: in which municipalities low-income consumers would have lower bills with PVDG compared to SET; which consumers in a given city would have increased subsidies, which are now provided for solar energy in Brazil and for the social tariff. An economic model was created for verifying the feasibility of the proposed policy in each municipality in the country, considering geographic issues (tariff of a particular distribution utility, radiation from a specific location, etc.). To validate these results, four sensitivity analyzes were performed: variation of the simultaneity factor between generation and consumption, variation of the tariff readjustment rate, zeroing CAPEX, and exemption from state tax. The behind-the-meter modality of generation proved to be more promising than the construction of a shared plant. However, although the behind-the-meter modality presents better results than the shared plant, there is a greater complexity in adopting this modality due to issues related to the infrastructure of the most vulnerable communities (e.g., precarious electrical networks, need to reinforce roofs). Considering the shared power plant modality, many opportunities are still envisaged since the risk of investing in such a policy can be mitigated. Furthermore, this modality can be an alternative due to the mitigation of the risk of default, as it allows greater control of users and facilitates the process of operation and maintenance. Finally, it was also found, that in some regions of Brazil, the continuity of the SET presents more economic benefits than its replacement by PVDG. However, the proposed policy offers many opportunities. For future works, the model may include other parameters, such as cost with low-income populations’ engagement, and business risk. In addition, other renewable sources of distributed generation can be studied for this purpose.

Keywords: low income, subsidy policy, distributed energy resources, energy justice

Procedia PDF Downloads 84

Authors: Elena Filova, Ondrej Kaplan, Marie Markova, Helena Dragounova, Roman Matejka, Eduard Brynda, Lucie Bacakova

Abstract:

Decellularized vessels have been evaluated as small-diameter vascular prostheses. Reseeding autologous cells onto decellularized tissue prior implantation should prolong prostheses function and make them living tissues. Suitable cell types for reseeding are both endothelial cells and bone marrow-derived stem cells, with a capacity for differentiation into smooth muscle cells upon mechanical loading. Endothelial cells assure antithrombogenicity of the vessels and MSCs produce growth factors and, after their differentiation into smooth muscle cells, they are contractile and produce extracellular matrix proteins as well. Fibrin is a natural scaffold, which allows direct cell adhesion based on integrin receptors. It can be prepared autologous. Fibrin can be modified with bound growth factors, such as basic fibroblast growth factor (FGF-2) and vascular endothelial growth factor (VEGF). These modifications in turn make the scaffold more attractive for cells ingrowth into the biological scaffold. The aim of the study was to prepare thin surface-attached fibrin assemblies with bound FGF-2 and VEGF, and to evaluate growth and differentiation of bone marrow-derived mesenchymal stem cells on the fibrin (Fb) assemblies. Following thin surface-attached fibrin assemblies were prepared: Fb, Fb+VEGF, Fb+FGF2, Fb+heparin, Fb+heparin+VEGF, Fb+heparin+FGF2, Fb+heparin+FGF2+VEGF. Cell culture poly-styrene and glass coverslips were used as controls. Human MSCs (passage 3) were seeded at the density of 8800 cells/1.5 mL alpha-MEM medium with 2.5% FS and 200 U/mL aprotinin per well of a 24-well cell culture. The cells have been cultured on the samples for 6 days. Cell densities on day 1, 3, and 6 were analyzed after staining with LIVE/DEAD cytotoxicity/viability assay kit. The differentiation of MSCs is being analyzed using qPCR. On day 1, the highest density of MSCs was observed on Fb+VEGF and Fb+FGF2. On days 3 and 6, there were similar densities on all samples. On day 1, cell morphology was polygonal and spread on all sample. On day 3 and 6, MSCs growing on Fb assemblies with FGF2 became apparently elongated. The evaluation of expression of genes for von Willebrand factor and CD31 (endothelial cells), for alpha-actin (smooth muscle cells), and for alkaline phosphatase (osteoblasts) is in progress. We prepared fibrin assemblies with bound VEGF and FGF-2 that supported attachment and growth of mesenchymal stem cells. The layers are promising for improving the ingrowth of MSCs into the biological scaffold. Supported by the Technology Agency of the Czech Republic TA04011345, and Ministry of Health NT11270-4/2010, and BIOCEV – Biotechnology and Biomedicine Centre of the Academy of Sciences and Charles University” project (CZ.1.05/1.1.00/02.0109), funded by the European Regional Development Fund for their financial supports.

Keywords: fibrin assemblies, FGF-2, mesenchymal stem cells, VEGF

Procedia PDF Downloads 301

Authors: Ignitia Motjolopane

Abstract:

Small and medium enterprises (SMEs) play an important role in economies by contributing to economic growth and employment. In the fourth industrial revolution, the convergence of technologies and the changing nature of work created pressures on economies globally. Generative artificial intelligence (AI) may support SMEs in exploring, exploiting, and transforming business models to align with their growth aspirations. SMEs' growth aspirations fall into four categories: subsistence, income, growth, and speculative. Subsistence-oriented firms focus on meeting basic financial obligations and show less motivation for business model innovation. SMEs focused on income, growth, and speculation are more likely to pursue business model innovation to support growth strategies. SMEs' strategic goals link to distinct business model innovation paths depending on whether SMEs are starting a new business, pursuing growth, or seeking profitability. Integrating generative artificial intelligence in start-up SME business model innovation enhances value creation, user-oriented innovation, and SMEs' ability to adapt to dynamic changes in the business environment. The existing literature may lack comprehensive frameworks and guidelines for effectively integrating generative AI in start-up reiterative business model innovation paths. This paper examines start-up business model innovation path with generative artificial intelligence. A theoretical approach is used to examine start-up-focused SME reiterative business model innovation path with generative AI. Articulating how generative AI may be used to support SMEs to systematically and cyclically build the business model covering most or all business model components and analyse and test the BM's viability throughout the process. As such, the paper explores generative AI usage in market exploration. Moreover, market exploration poses unique challenges for start-ups compared to established companies due to a lack of extensive customer data, sales history, and market knowledge. Furthermore, the paper examines the use of generative AI in developing and testing viable value propositions and business models. In addition, the paper looks into identifying and selecting partners with generative AI support. Selecting the right partners is crucial for start-ups and may significantly impact success. The paper will examine generative AI usage in choosing the right information technology, funding process, revenue model determination, and stress testing business models. Stress testing business models validate strong and weak points by applying scenarios and evaluating the robustness of individual business model components and the interrelation between components. Thus, the stress testing business model may address these uncertainties, as misalignment between an organisation and its environment has been recognised as the leading cause of company failure. Generative AI may be used to generate business model stress-testing scenarios. The paper is expected to make a theoretical and practical contribution to theory and approaches in crafting a robust business model innovation path with generative artificial intelligence in start-up SMEs.

Keywords: business models, innovation, generative AI, small medium enterprises

Procedia PDF Downloads 44

Authors: Huseyin Apdik, Aysegul Dogan, Selami Demirci, Ezgi Avsar Apdik, Fikrettin Sahin

Abstract:

Mesenchymal stem cells (MSCs) are crucial cell types for bone maintenance and growth along with resident bone progenitor cells providing bone tissue integrity during osteogenesis and skeletal growth. Any deficiency in this regulation would result in vital bone diseases. Of those, osteoporosis, characterized by a reduction in bone mass and mineral density, is a critical skeletal disease for especially elderly people. The commonly used drugs for the osteoporosis treatment are bisphosphonates (BPs). The most prominent role of BPs is to prevent bone resorption arisen from high osteoclast activity. However, administrations of bisphosphonates may also cause bisphosphonate-induced osteonecrosis of the jaw (BIONJ). Up to the present, the researchers have proposed several circumstances for BIONJ. However, effects of long-term and/or high dose usage of BPs on stem cell’s proliferation, survival, differentiation or maintenance capacity have not been evaluated yet. The present study will be held to; figure out BPs’ effects on MSCs in vitro in the aspect of cell proliferation and toxicity, migration, angiogenic activity, lineage specific gene and protein expression levels, mesenchymal stem cell properties and potential signaling pathways affected by BP treatment. Firstly, mesenchymal stem cell characteristics of Dental Pulp Stem Cells (DPSCs) and Periodontal Ligament Stem Cells (PDLSCs) were proved using flow cytometry analysis. Cell viability analysis was completed to determine the cytotoxic effects of BPs (Zoledronate (Zol), Alendronate (Ale) and Risedronate (Ris)) on DPSCs and PDLSCs by the 3-(4,5-di-methyl-thiazol-2-yl)-5-(3-carboxymethoxy-phenyl)-2-(4-sulfo-phenyl)-2H-tetrazolium (MTS) assay. Non-toxic concentrations of BPs were determined at 24 h under growth condition, and at 21 days under osteogenic differentiation condition for both cells. The scratch assay was performed to evaluate their migration capacity under the usage of determined of BPs concentrations at 24 h. The results revealed that while the scratch closure is 70% in the control group for DPSCs, it was 57%, 66% and 66% in Zol, Ale and Ris groups, respectively. For PDLSs, while wound closure is 71% in control group, it was 65%, 66% and 66% in Zol, Ale and Ris groups, respectively. As future experiments, tube formation assay and aortic ring assay will be done to determinate angiogenesis abilities of DPSCs and PDLSCs treated with BPs. Expression levels of osteogenic differentiation marker genes involved in bone development will be determined using real time-polymerase change reaction (RT-PCR) assay and expression profiles of important proteins involved in osteogenesis will be evaluated using western blotting assay for osteogenically differentiated MSCs treated with or without BPs. In addition to these, von Kossa staining will be performed to measure calcium mineralization status of MSCs.

Keywords: bisphosphonates, bisphosphonate-induced osteonecrosis of the jaw, mesenchymal stem cells, osteogenesis

Procedia PDF Downloads 240

Authors: Damian Graham, Ashleigh H. Hall, Damani R. Sulph, Michael A. James, Shawn B. Vassell

Abstract:

This paper assesses the design and feasibility of a Materials Recovery Facility (MRF) in Jamaica as a possible green industry approach to the nation’s economic and solid waste management problems. Jamaica is a developing nation that is vulnerable to climate change that can affect its blue economy and tourism on which it is heavily reliant. Jamaica’s National Solid Waste Management Authority (NSWMA) collects only a fraction of all the solid waste produced annually which is then transported to dumpsites. The remainder is either burnt by the population or disposed of illegally. These practices negatively impact the environment, threaten the sustainability of economic growth from blue economy and tourism and its waste management system is predominantly a cost centre. The implementation of an MRF could boost the manufacturing sector, contribute to economic growth, and be a catalyst in creating a green industry with multiple downstream value chains with supply chain linkages. Globally, there is a trend to reuse and recycle that created an international market for recycled solid waste. MRFs enable the efficient sorting of solid waste into desired recoverable materials thus providing a gateway for entrance to the international trading of recycled waste. Research into the current state and effort to improve waste management in Jamaica in contrast with the similar and more advanced territories are outlined. The study explores the concept of green industrialization and its applicability to vulnerable small state economies like Jamaica. The study highlights the possible contributions and benefits derived from MRFs as a seeding factory that can anchor the reverse and forward logistics of other green industries as part of a logistic-cantered economy. Further, the study showcases an engineering economic analysis that assesses the viability of the implementation of an MRF in Jamaica. This research outlines the potential cost of constructing and operating an MRF and provides a realistic cash flow estimate to establish a baseline for profitability. The approach considers quantitative and qualitative data, assumptions, and modelling using industrial engineering tools and techniques that are outlined. Techniques of facility planning, system analysis and operations research with a focus on linear programming techniques are expressed. Approaches to overcome some implementation challenges including policy, technology and public education are detailed. The results of this study present a reasonable judgment of the prospects of incorporating an MRF to improve Jamaica’s solid waste management and contribute to socioeconomic and environmental benefits and an alternate pathway for economic sustainability.

Keywords: engineering-economic analysis, facility design, green industry, MRF, manufacturing, plant layout, solid-waste management, sustainability, waste disposal

Procedia PDF Downloads 193

Authors: Nonita Sarin, K.J.Singh, Anuj Kumar, Davinder Singh

Abstract:

Polymeric 3D hydrogels have pivotal role in bone tissue regeneration applications. Hydrogels behave similar to the living tissues because they have large water imbibing capacity in swollen state and adjust their shape according to the tissues during tissue formation after implantation. On the other hand, hydrogels are very soft, fragile and lack mechanical strength. Incorporation of bioceramics can improve mechanical strength. Furthermore, bioceramics synthesized by sol gel technique may enhance the apatite formation and degradation rates which can lead to the increase in faster rates for new bone and tissue regeneration. Simulated body fluid (SBF) induces the poly-condensation of silanol groups which leads to formation of silica matrix and provide active sites for the precipitation of Ca2+ and PO43- ions to form apatite layer which is similar to mineral form of bone. Therefore, authors have synthesized bioceramic incorporated Polyacrylamide-carboxymethylcellulose hydrogels by free radical polymerization and bioceramic compositions of xSrO-(36-x)CaO-45SiO2-ySeO3-(12-y)P2O5-7MgO (where x=0,4 and y=0,2 mol%) were synthesized by sol gel technique. Bioceramics incorporated in polymer matrix induces quicker apatite formation during immersion in SBF by raising the pH with the release of alkaline ions during ion exchange process and the apatite formation takes place in alkaline medium. The behavior of samples PABC-0 (without bioceramics) and PABC-20 (with 20 wt% bioceramics) were evaluated by X-Ray Diffraction and FTIR. In term of bioactivity, it was observed that PABC-20 has shown hydroxyapatite (HA) formation on 1st day of immersion whereas, PABC-0 was shown apatite formation on 7th day of immersion in SBF. The rapid rate of HA growth on 1st day of immersion in SBF signifies easy regeneration of damaged bone tissues. Degradation studies have been undertaken in Phosphate Buffer Saline and PABC-20 exhibited slower degradation rate up to 9%as compared to PABC-0 up to 18%. Slower degradation rate is suitable for new tissue regeneration and cell attachment. Also, Zeta potential studies have been employed to check the surface charge and it has been observed that samples carry negative charge when immersed in SBF. In addition, the swelling test of the samples have been performed and relative swelling ratio % observed for PABC-0 is 607% and PABC-20 is 305%. This indicates that the incorporation of bioceramics leads to the filling up of the voids in between the polymer matrix which in result reduces porosity and increase the mechanical strength by filling the voids. The porosity of PABC-0 is 84% and PABC-20 is 72%. PABC-20 sample demonstrates that bioceramics incorporation reduce the porosity and improves mechanical strength. Also, maximum in vitro cell viability up to 98% with MG63 cell line has been observed which indicate that the bioceramic incorporated hydrogel(PABC-20) provide the alkaline medium which is suitable environment for cell growth.

Keywords: hydrogels, hydroxyapatite, MG63 cell line, zeta potential

Procedia PDF Downloads 115

Authors: Magda Mahmoud Amin Sabbour, El-Sayed H. Shaurub

Abstract:

The Indian meal moth Plodia interpunctella (Hübner) (Lepidoptera: Pyralidae), of stored grain pests which destroy the seed completely. Their larval stages feed on the nutrient germinating kernels part found in the seeds grain. This leads to a reduction causing a badness to seed germination and seed viability. It controlled by many insecticides which pollute and cusses a harmful diseases to human being. Three tested oils were evaluated on this target pests. Plant extracts, essential oils and medical oils are materials which used to control many stored pests. Plant oils extracts have a lower effects on parasites and predators and not pollute the medium. By using the apparatus gas chromatography flame ionization detector gas chromatography–analysis of three essential oil tested. This research was point to explore and appreciation the activity of three oils and nano gel Beauvericin against P. interpunctella in the laboratory conditions and in the store conditions. The three essential oil tested proved that, percentage of α-Pinene recoded 7.76, 7.72 and 6.66 for C. cyminum, A. squamosal and G. officinale respectively. The composition of the β-Pinene recoded 4.61, 8.92 and 30.63 for the corresponding oils tested. Results showed that after analytically the oils tested, the effective compound of C. cyminum oil are p-cyinene and Terpinene. Results obtained show that the LC50 recorded 125, 112, 55 and 20 ppm after P. interpunctella treated with medical oils of Guaiacum officinale, Annona squamosa, Cuminum cyminum and Beauvericin 3% respectively. The accumulative mortality of P. interpunctella after treated with A.squamosa oil-loaded nanogels which showed that it is the highest oils from infestations recoded when the seed treated with 3% after 48 days, the accumulations obtained 44% at followed by 24 after24 days of storage. Results, cleared that the seed protection by G. officinale recorded 40% at concentrations of 3% after 48 days of storage seeds. C. cyminum was the highest mortality by 98, at concentrations 3%. The highest seed protection proved after C. cyminum oil-loaded nanogels 14% followed by G. officinale 29% and A.squamosa 44%.when the seeds treated with Beauvericin 3%. Results of this work cleared that the essential medical oils have a useful action effect on target insects. Plant essential and medical oils, their active ingredient have potentially high bioactivity against on P. interpunctella. The medical and essential oils incorporation and usage the nano-formulation release stopped the highly degradation vaporization and the increasing in the constancy, and save the lower effectiveness of the dosage/application. The research results proved that the highest seed protection obtained after C. cyminum oil-loaded nanogels followed by G. officinale and A.squamosa. It could be complemented that P. interpunctella were more susceptible to medical oils loaded nanogel (MOLNs ) than medical oils only (MO). MOLNs had best lower amount of the residual activity than MO only. MOLNs might mend the insecticidal action of the medical oil tested by the slow effective release of the medical oils to control P. interpunctella mostly at the lower doses.

Keywords: Cuminum cyminum, annona squamosa, guaiacum officinale, beauvericin 3 %, plodia interpunctella

Procedia PDF Downloads 87

Authors: Chetna Dhand, Venkatesh Mayandi, Silvia Marrero Diaz, Roger W. Beuerman, Seeram Ramakrishna, Rajamani Lakshminarayanan

Abstract:

Sturdy Insect Cuticle Sclerotization, Incredible Substrate independent Mussel’s bioadhesion, Tanning of Leather are some of catechol(amine)s mediated natural processes. Chemical contemplation spots toward a mechanism instigated with the formation of the quinone moieties from the respective catechol(amine)s, via oxidation, followed by the nucleophilic addition of the amino acids/proteins/peptides to this quinone leads to the development of highly strong, cross-linked and water-resistant proteinacious structures. Inspired with this remarkable catechol(amine)s chemistry towards amino acids/proteins/peptides, we attempted to design highly stable and water-resistant antifungal wound dressing mats with exceptional durability using collagen (protein), dopamine (catecholamine) and antifungal drugs (Amphotericin B and Caspofungin) as the key materials. Electrospinning technique has been used to fabricate desired nanofibrous mat including Collagen (COLL), COLL/Dopamine (COLL/DP) and calcium incorporated COLL/DP (COLL-DP-Ca2+). The prepared protein-based scaffolds have been studied for their microscopic investigations (SEM, TEM, and AFM), structural analysis (FT-IR), mechanical properties, water wettability characteristics and aqueous stability. Biocompatibility of these scaffolds has been analyzed for dermal fibroblast cells using MTS assay, Cell TrackerTM Green CMFDA and confocal imaging. Being the winner sample, COLL-DP-Ca2+ scaffold has been selected for incorporating two antifungal drugs namely Caspofungin (Peptide based) and Amphotericin B (Non-Peptide based). Antifungal efficiency of the designed mats has been evaluated for eight diverse fungal strains employing different microbial assays including disc diffusion, cell-viability assay, time kill kinetics etc. To confirm the durability of these mats, in term of their antifungal activity, drug leaching studies has been performed and monitored using disc diffusion assay each day. Ex-vivo fungal infection model has also been developed and utilized to validate the antifungal efficacy of the designed wound dressings. Results clearly reveal dopamine mediated crosslinking within COLL-antifungal scaffolds that leads to the generation of highly stable, mechanical tough, biocompatible wound dressings having the zone of inhabitation of ≥ 2 cm for almost all the investigated fungal strains. Leaching studies and Ex-vivo model has confirmed the durability of these wound dressing for more than 3 weeks and certified their suitability for commercialization. A model has also been proposed to enlighten the chemical mechanism involved for the development of these antifungal wound dressings with exceptional robustness.

Keywords: catecholamine chemistry, electrospinning technique, antifungals, wound dressings, collagen

Procedia PDF Downloads 347

Authors: Sumeet Rai, Anuj Tyagi, B. T. Naveen Kumar, Shubhkaramjeet Kaur, Niraj K. Singh

Abstract:

Since their discovery, indiscriminate use of antibiotics in human, veterinary and aquaculture systems has resulted in global emergence/spread of multidrug-resistant bacterial pathogens. Thus, the need for alternative approaches to control bacterial infections has become utmost important. High selectivity/specificity of bacteriophages (phages) permits the targeting of specific bacteria without affecting the desirable flora. In this study, a lytic phage (Ahp1) specific to Aeromonas hydrophila subsp. hydrophila was isolated from finfish aquaculture pond. The host range of Ahp1 range was tested against 10 isolates of A. hydrophila, 7 isolates of A. veronii, 25 Vibrio cholerae isolates, 4 V. parahaemolyticus isolates and one isolate each of V. harveyi and Salmonella enterica collected previously. Except the host A. hydrophila subsp. hydrophila strain, no lytic activity against any other bacterial was detected. During the adsorption rate and one-step growth curve analysis, 69.7% of phage particles were able to get adsorbed on host cell followed by the release of 93 ± 6 phage progenies per host cell after a latent period of ~30 min. Phage nucleic acid was extracted by column purification methods. After determining the nature of phage nucleic acid as dsDNA, phage genome was subjected to next-generation sequencing by generating paired-end (PE, 2 x 300bp) reads on Illumina MiSeq system. De novo assembly of sequencing reads generated circular phage genome of 42,439 bp with G+C content of 58.95%. During open read frame (ORF) prediction and annotation, 22 ORFs (out of 49 total predicted ORFs) were functionally annotated and rest encoded for hypothetical proteins. Proteins involved in major functions such as phage structure formation and packaging, DNA replication and repair, DNA transcription and host cell lysis were encoded by the phage genome. The complete genome sequence of Ahp1 along with gene annotation was submitted to NCBI GenBank (accession number MF683623). Stability of Ahp1 preparations at storage temperatures of 4 °C, 30 °C, and 40 °C was studied over a period of 9 months. At 40 °C storage, phage counts declined by 4 log units within one month; with a total loss of viability after 2 months. At 30 °C temperature, phage preparation was stable for < 5 months. On the other hand, phage counts decreased by only 2 log units over a period of 9 during storage at 4 °C. As some of the phages have also been reported as glycerol sensitive, the stability of Ahp1 preparations in (0%, 15%, 30% and 45%) glycerol stocks were also studied during storage at -80 °C over a period of 9 months. The phage counts decreased only by 2 log units during storage, and no significant difference in phage counts was observed at different concentrations of glycerol. The Ahp1 phage discovered in our study had a very narrow host range and it may be useful for phage typing applications. Moreover, the endolysin and holin genes in Ahp1 genome could be ideal candidates for recombinant cloning and expression of antimicrobial proteins.

Keywords: Aeromonas hydrophila, endolysin, phage, narrow host range

Procedia PDF Downloads 146

Authors: S. Kudlacik-Kramarczyk, M. Kedzierska, B. Tyliszczak

Abstract:

Recently, the continuous development of medicine and related sciences has been observed. Particular emphasis is directed on the development of biomaterials, i.e., non-toxic, biocompatible and biodegradable materials that may improve the effectiveness of treatment as well as the comfort of patients. This is particularly important in the case of cancer treatment. Currently, there are many methods of cancer treatment based primarily on chemotherapy and the surgical removal of the tumor, but it is worth noting that these therapies also cause many side effects. Among women, the most common cancer is breast cancer. It may be completely cured, but the consequence of treatment is partial or complete breast mastectomy and radiation therapy, which results in severe skin burns. The skin of the patient after radiation therapy is very burned, and therefore requires intensive care and high frequency of dressing changes. The traditional dressing adheres to the burn wounds and does not absorb adequate amount of exudate from injuries and the patient is forced to change the dressing every 2 hours. Therefore, the main purpose was to develop an innovative combination of dressing material with drug carriers that may be used in anti-cancer therapy. The innovation of this solution is the combination of these two products into one system, i.e., a transdermal system with the possibility of a controlled release of the drug- cytostatic. Besides, the possibility of modifying the hydrogel matrix with aloe vera juice provides this material with new features favorable from the point of view of healing processes of burn wounds resulting from the radiation therapy. In this study, hydrogel materials containing protein spheres with the active substance have been obtained as a result of photopolymerization process. The reaction mixture consisting of the protein (albumin) spheres incorporated with cytostatic, chitosan, adequate crosslinking agent and photoinitiator has been subjected to the UV radiation for 2 minutes. Prepared materials have been subjected to the numerous studies including the analysis of cytotoxicity using murine fibroblasts L929. Analysis was conducted based on the mitochondrial activity test (MTT reduction assay) which involves the determining the number of cells characterized by proper metabolism. Hydrogel materials obtained using different amount of crosslinking agents have been subjected to the cytotoxicity analysis. According to the standards, tested material is defined as cytotoxic when the viability of cells after 24 h incubation with this material is lower than 70%. In the research, hydrogel polymer materials containing protein spheres incorporated with the active substance, i.e. a cytostatic, have been developed. Such a dressing may support the treatment of cancer due to the content of the anti-cancer drug - cytostatic, and may also provide a soothing effect on the healing of the burn wounds resulted from the radiation therapy due to the content of aloe vera juice in the hydrogel matrix. Based on the conducted cytotoxicity studies, it may be concluded that the obtained materials do not adversely affect the tested cell lines, therefore they can be subjected to more advanced analyzes.

Keywords: hydrogel polymers, cytostatics, drug carriers, cytotoxicity

Procedia PDF Downloads 112

Authors: Kiana Taheri

Abstract:

Rural tourism has garnered significant attention as a catalyst for rural development and sustainability, particularly in regions like Tuscany, Italy, where the convergence of cultural heritage, picturesque landscapes, and agricultural traditions provides a fertile ground for tourism activities. This paper investigates the pivotal role of women entrepreneurs in driving sustainable rural tourism development, with a specific focus on Tuscany. Drawing upon a synthesis of literature on rural tourism, entrepreneurship, and gender studies, this research offers insights into how women entrepreneurs contribute to the economic, social, and environmental dimensions of rural tourism in Tuscany. The conceptual framework of this study is rooted in the evolving landscape of rural development, shaped by shifting paradigms in agricultural policies, such as the Common Agricultural Policy (CAP) of the European Union. This framework underscores the transition from traditional agrarian economies to dynamic rural tourism destinations characterized by a consumer-centric approach and a focus on sustainable development. Against this backdrop, the study delves into the multifaceted contributions of women entrepreneurs within the rural tourism sector. Central to the analysis is the recognition of rural tourism as a nexus of social, cultural, economic, and environmental interactions, wherein women entrepreneurs play a pivotal role in leveraging local resources, preserving cultural heritage, and fostering community engagement. By capitalizing on their unique perspectives, skills, and networks, women entrepreneurs drive innovation, diversification, and inclusivity within the tourism sector, thereby enhancing its resilience and long-term viability. Moreover, the study highlights the symbiotic relationship between rural tourism development and women's empowerment, as evidenced by the increasing prominence of women entrepreneurs in Tuscany's rural economy. Through their leadership roles in small and medium enterprises (SMEs) and agritourism ventures, women entrepreneurs not only contribute to economic growth but also challenge traditional gender norms and empower local communities. A key empirical focus of this research is a comprehensive case study of Tuscany, renowned for its successful rural tourism model and vibrant entrepreneurial ecosystem. Through qualitative interviews, surveys, and archival analysis, the study elucidates the strategies, challenges, and impacts of women entrepreneurs on sustainable rural tourism development in Tuscany. By examining the experiences of women entrepreneurs across diverse sectors of rural tourism, including hospitality, gastronomy, and cultural heritage, the study offers nuanced insights into their contributions to regional development and empowerment. In conclusion, this research contributes to the burgeoning scholarship on rural tourism, entrepreneurship, and gender studies by shedding light on the transformative role of women entrepreneurs in driving sustainable development agendas in rural areas. By elucidating the interplay between gender dynamics, entrepreneurial activities, and tourism development, this study seeks to inform policy interventions and strategic initiatives aimed at fostering inclusive and sustainable rural tourism ecosystems.

Keywords: rural tourism, women empowerment, entrepreneurship, sustainable development, small and medium-sized enterprises (SMEs)

Procedia PDF Downloads 18

Authors: Alberto Veses, Olga Sanhauja, María Soledad Callén, Tomás García

Abstract:

The appropriate use of renewable sources emerges as a decisive point to minimize the environmental impact caused by fossil fuels use. Particularly, the use of lignocellulosic biomass becomes one of the best promising alternatives since it is the only carbon-containing renewable source that can produce bioproducts similar to fossil fuels and it does not compete with food market. Among all the processes that can valorize lignocellulosic biomass, pyrolysis is an attractive alternative because it is the only thermochemical process that can produce a liquid biofuel (bio-oil) in a simple way and solid and gas fractions that can be used as energy sources to support the process. However, in order to incorporate bio-oils in current infrastructures and further process in future biorefineries, their quality needs to be improved. Introducing different low-cost catalysts and/or incorporating different polymer residues to the process are some of the new, simple and low-cost strategies that allow the user to directly obtain advanced bio-oils to be used in future biorefineries in an economic way. In this manner, from previous thermogravimetric analyses, local agricultural wastes such as grape seeds (GS) were selected as lignocellulosic biomass while, waste tires (WT) were selected as polymer residue. On the other hand, CaO was selected as low-cost catalyst based on previous experiences by the group. To reach this aim, a specially-designed fixed bed reactor using N₂ as a carrier gas was used. This reactor has the peculiarity to incorporate a vertical mobile liner that allows the user to introduce the feedstock in the oven once the selected temperature (550 ºC) is reached, ensuring higher heating rates needed for the process. Obtaining a well-defined phase distribution in the resulting bio-oil is crucial to ensure the viability to the process. Thus, once experiments were carried out, not only a well-defined two layers was observed introducing several mixtures (reaching values up to 40 wt.% of WT) but also, an upgraded organic phase, which is the one considered to be processed in further biorefineries. Radical interactions between GS and WT released during the pyrolysis process and dehydration reactions enhanced by CaO can promote the formation of better-quality bio-oils. The latter was reflected in a reduction of water and oxygen content of bio-oil and hence, a substantial increase of its heating value and its stability. Moreover, not only sulphur content was reduced from solely WT pyrolysis but also potential and negative issues related to a strong acidic environment of conventional bio-oils were minimized due to its basic pH and lower total acid numbers. Therefore, acidic compounds obtained in the pyrolysis such as CO₂-like substances can react with the CaO and minimize acidic problems related to lignocellulosic bio-oils. Moreover, this CO₂ capture promotes H₂ production from water gas shift reaction favoring hydrogen-transfer reactions, improving the final quality of the bio-oil. These results show the great potential of grapes seeds to carry out the catalytic co-pyrolysis process with different plastic residues in order to produce a liquid bio-oil that can be considered as a high-quality renewable vector.

Keywords: advanced bio-oils, biorefinery, catalytic co-pyrolysis of biomass and waste tires, lignocellulosic biomass

Procedia PDF Downloads 214

Authors: Elena I. Oprita, Oana Craciunescu, Rodica Tatia, Teodora Ciucan, Reka Barabas, Orsolya Raduly, Anca Oancea

Abstract:

Healing of osteochondral defects requires repair of the damaged articular cartilage, the underlying subchondral bone and the interface between these tissues (the functional calcified layer). For this purpose, developing a single monophasic scaffold that can regenerate two specific lineages (cartilage and bone) becomes a challenge. The aim of this work was to develop variants of biodegradable cross-linked composite hydrogel based on natural polypeptides (gelatin), polysaccharides components (chondroitin-4-sulphate and hyaluronic acid), in a ratio of 2:0.08:0.02 (w/w/w) and mixed with Si-hydroxyapatite (Si-Hap), in two ratios of 1:1 and 2:1 (w/w). Si-Hap was synthesized and characterized as a better alternative to conventional Hap. Subsequently, both composite hydrogel variants were cross-linked with (N, N-(3-dimethylaminopropyl)-N-ethyl carbodiimide (EDC) and enriched with a small bioactive molecule (icariin). The small molecule icariin (Ica) (C33H40O15) is the main active constituent (flavonoid) of Herba epimedium used in traditional Chinese medicine to cure bone- and cartilage-related disorders. Ica enhances osteogenic and chondrogenic differentiation of bone marrow mesenchymal stem cells (BMSCs), facilitates matrix calcification and increases the specific extracellular matrix (ECM) components synthesis by chondrocytes. Afterward, the composite hydrogels were characterized for their physicochemical properties in terms of the enzymatic biodegradation in the presence of type I collagenase and trypsin, the swelling capacity and the degree of crosslinking (TNBS assay). The cumulative release of Ica and real-time concentration were quantified at predetermined periods of time, according to the standard curve of standard Ica, after hydrogels incubation in saline buffer at physiological parameters. The obtained cross-linked composite hydrogels enriched with small-molecule Ica were also characterized for morphology by scanning electron microscopy (SEM). Their cytocompatibility was evaluated according to EN ISO 10993-5:2009 standard for medical device testing. Thus, analyses regarding cell viability (Live/Dead assay), cell proliferation (Neutral Red assay) and cell adhesion to composite hydrogels (SEM) were performed using NCTC clone L929 cell line. The final results showed that both cross-linked composite hydrogel variants enriched with Ica presented optimal physicochemical, structural and biological properties to be used as a natural scaffold able to repair osteochondral defects. The data did not reveal any toxicity of composite hydrogels in NCTC stabilized cell lines within the tested range of concentrations. Moreover, cells were capable of spreading and proliferating on both composite hydrogel surfaces. In conclusion, the designed biodegradable cross-linked composites enriched with Si and Ica are recommended for further testing as natural temporary scaffolds, which can allow cell migration and synthesis of new extracellular matrix within osteochondral defects.

Keywords: composites, gelatin, osteochondral defect, small molecule

Procedia PDF Downloads 151

Authors: G. Cunningham, E. Cantor, X. Wu, F. Shen, G. Jiang, S. Philips, C. Bales, Y. Xiao, T. R. Cummins, J. C. Fehrenbacher, B. P. Schneider

Abstract:

Background: Taxane-induced peripheral neuropathy (TIPN) is the most devastating survivorship issue for patients receiving therapy. Dose reductions due to TIPN in the curative setting lead to inferior outcomes for African American patients, as prior research has shown that this group is more susceptible to developing severe neuropathy. The mechanistic underpinnings of TIPN, however, have not been entirely elucidated. While it would be appealing to use primary tissue to study the development of TIPN, procuring nerves from patients is not realistically feasible, as nerve biopsies are painful and may result in permanent damage. Therefore, our laboratory has investigated paclitaxel-induced neuronal morphological and molecular changes using an ex vivo model of human-induced pluripotent stem cell (iPSC)-derived neurons. Methods: iPSCs are undifferentiated and endlessly dividing cells that can be generated from a patient’s somatic cells, such as peripheral blood mononuclear cells (PBMCs). We successfully reprogrammed PBMCs into iPSCs using the Erythroid Progenitor Reprograming Kit (STEMCell Technologiesᵀᴹ); pluripotency was verified by flow cytometry analysis. iPSCs were then induced into neurons using a differentiation protocol that bypasses the neural progenitor stage and uses selected small-molecule modulators of key signaling pathways (SMAD, Notch, FGFR1 inhibition, and Wnt activation). Results: Flow cytometry analysis revealed expression of core pluripotency transcription factors Nanog, Oct3/4 and Sox2 in iPSCs overlaps with commercially purchased pluripotent cell line UCSD064i-20-2. Trilineage differentiation of iPSCs was confirmed with immunofluorescent imaging with germ-layer-specific markers; Sox17 and ExoA2 for ectoderm, Nestin, and Pax6 for mesoderm, and Ncam and Brachyury for endoderm. Sensory neuron markers, β-III tubulin, and Peripherin were applied to stain the cells for the maturity of iPSC-derived neurons. Patch-clamp electrophysiology and calcitonin gene-related peptide (CGRP) release data supported the functionality of the induced neurons and provided insight into the timing for which downstream assays could be performed (week 4 post-induction). We have also performed a cell viability assay and fluorescence-activated cell sorting (FACS) using four cell-surface markers (CD184, CD44, CD15, and CD24) to select a neuronal population. At least 70% of the cells were viable in the isolated neuron population. Conclusion: We have found that these iPSC-derived neurons recapitulate mature neuronal phenotypes and demonstrate functionality. Thus, this represents a patient-derived ex vivo neuronal model to investigate the molecular mechanisms of clinical TIPN.

Keywords: chemotherapy, iPSC-derived neurons, peripheral neuropathy, taxane, paclitaxel

Procedia PDF Downloads 100

Authors: Ernest Moles, Patricia Urbán, María Belén Jiménez-Díaz, Sara Viera-Morilla, Iñigo Angulo-Barturen, Maria Antònia Busquets, Xavier Fernàndez-Busquets

Abstract:

Bearing in mind the absence of an effective vaccine against malaria and its severe clinical manifestations causing nearly half a million deaths every year, this disease represents nowadays a major threat to life. Besides, the basic rationale followed by currently marketed antimalarial approaches is based on the administration of drugs on their own, promoting the emergence of drug-resistant parasites owing to the limitation in delivering drug payloads into the parasitized erythrocyte high enough to kill the intracellular pathogen while minimizing the risk of causing toxic side effects to the patient. Such dichotomy has been successfully addressed through the specific delivery of immunoliposome (iLP)-encapsulated antimalarials to Plasmodium falciparum-infected red blood cells (pRBCs). Unfortunately, this strategy has not progressed towards clinical applications, whereas in vitro assays rarely reach drug efficacy improvements above 10-fold. Here, we show that encapsulation efficiencies reaching >96% can be achieved for the weakly basic drugs chloroquine (CQ) and primaquine using the pH gradient active loading method in liposomes composed of neutrally charged, saturated phospholipids. Targeting antibodies are best conjugated through their primary amino groups, adjusting chemical crosslinker concentration to retain significant antigen recognition. Antigens from non-parasitized RBCs have also been considered as targets for the intracellular delivery of drugs not affecting the erythrocytic metabolism. Using this strategy, we have obtained unprecedented nanocarrier targeting to early intraerythrocytic stages of the malaria parasite for which there is a lack of specific extracellular molecular tags. Polyethylene glycol-coated liposomes conjugated with monoclonal antibodies specific for the erythrocyte surface protein glycophorin A (anti-GPA iLP) were capable of targeting 100% RBCs and pRBCs at the low concentration of 0.5 μM total lipid in the culture, with >95% of added iLPs retained into the cells. When exposed for only 15 min to P. falciparum in vitro cultures synchronized at early stages, free CQ had no significant effect over parasite viability up to 200 nM drug, whereas iLP-encapsulated 50 nM CQ completely arrested its growth. Furthermore, when assayed in vivo in P. falciparum-infected humanized mice, anti-GPA iLPs cleared the pathogen below detectable levels at a CQ dose of 0.5 mg/kg. In comparison, free CQ administered at 1.75 mg/kg was, at most, 40-fold less efficient. Our data suggest that this significant improvement in drug antimalarial efficacy is in part due to a prophylactic effect of CQ found by the pathogen in its host cell right at the very moment of invasion.

Keywords: immunoliposomal nanoparticles, malaria, prophylactic-therapeutic polyvalent activity, targeted drug delivery

Procedia PDF Downloads 347

Authors: Roberta Pecoraro, Elena Maria Scalisi

Abstract:

Engineered Nanoparticles (ENPs) and Nanomaterials (ENMs) concern an active research area and a sector in full expansion. They have physical-chemical characteristics and small size that improve their performance compared to common materials. Due to the increase in their production and their subsequent release into the environment, new strategies are emerging to assess risk of nanomaterials. NPs can be released into the environment through aquatic systems by human activities and exert toxicity on living organisms. We evaluated the potential toxic effect of cerium oxide (CeO2) nanoparticles because it’s used in different fields due to its peculiar properties. In order to assess nanoparticles toxicity, Fish Embryo Toxicity (FET) test was performed. Powders of CeO2 NPs supplied by the CNR-IMM of Catania are indicated as CeO2 type 1 (as-prepared) and CeO2 type 2 (modified), while CeO2 type 3 (commercial) is supplied by Sigma-Aldrich. Starting from a stock solution (0.001g/10 ml dilution water) of each type of CeO2 NPs, the other concentration solutions were obtained adding 1 ml of the stock solution to 9 ml of dilution water, leading to three different solutions of concentration (10-4, 10-5, 10-6 g/ml). All the solutions have been sonicated to avoid natural tendency of NPs to aggregate and sediment. FET test was performed according to the OECD guidelines for testing chemicals using our internal protocol procedure. A number of eight selected fertilized eggs were placed in each becher filled with 5 ml of each concentration of the three types of CeO2 NPs; control samples were incubated only with dilution water. Replication was performed for each concentration. During the exposure period, we observed four endpoints (embryo coagulation, lack of formation of somites, failure to lift the yolk bag, no heartbeat) by a stereomicroscope every 24 hours. Immunohistochemical analysis on treated larvae was performed to evaluate the expression of metallothioneins (MTs), Heat Shock Proteins 70 (HSP70) and 7-ethoxyresorufin-O-diethylase (EROD). Our results have not shown evident alterations on embryonic development because all embryos completed the development and the hatching of the eggs, started around the 48th hour after exposure, took place within the last observation at 72 hours. A good reactivity, both in the embryos and in the newly hatched larvae, was found. The presence of heartbeat has also been observed in embryos with reduced mobility confirming their viability. A higher expression of EROD biomarker was observed in the larvae exposed to the three types of CeO2, showing a clear difference with the control. A weak positivity was found for MTs biomarker in treated larvae as well as in the control. HSP70 are expressed homogeneously in all the type of nanoparticles tested but not too much greater than control. Our results are in agreement with other studies in the literature, in which the exposure of Danio rerio larvae to other metal oxide nanoparticles does not show adverse effects on survival and hatching time. Further studies are necessary to clarify the role of these NPs and also to solve conflicting opinions.

Keywords: Danio rerio, endpoints, fish embryo toxicity test, metallic nanoparticles

Procedia PDF Downloads 102

Authors: Purva Nemavarkar, Badri Narain Pandey, Jitendra Kumar

Abstract:

Introduction: The objective was to understand the effect of various radioprotectors on DNA damage repair enzyme and survival in gamma-irradiated wild and cdc mutants of S. pombe (fission yeast) cultured under permissive and restrictive conditions. DNA repair process, as influenced by radioprotectors, was measured by activity of DNA polymerase in the cells. The use of single cell gel electrophoresis assay (SCGE) or Comet Assay to follow gamma-irradiation induced DNA damage and effect of radioprotectors was employed. In addition, studying the effect of caffeine at different concentrations on S-phase of cell cycle was also delineated. Materials and Methods: S. pombe cells grown at permissive temperature (250C) and/or restrictive temperature (360C) were followed by gamma-radiation. Percentage survival and activity of DNA Polymerase (yPol II) were determined after post-irradiation incubation (5 h) with radioprotectors such as Caffeine, Curcumin, Disulphiram, and Ellagic acid (the dose depending on individual D 37 values). The gamma-irradiated yeast cells (with and without the radioprotectors) were spheroplasted by enzyme glusulase and subjected to electrophoresis. Radio-resistant cells were obtained by arresting cells in S-phase using transient treatment of hydroxyurea (HU) and studying the effect of caffeine at different concentrations on S-phase of cell cycle. Results: The mutants of S. pombe showed insignificant difference in survival when grown under permissive conditions. However, growth of these cells under restrictive temperature leads to arrest in specific phases of cell cycle in different cdc mutants (cdc10: G1 arrest, cdc22: early S arrest, cdc17: late S arrest, cdc25: G2 arrest). All the cdc mutants showed decrease in survival after gamma radiation when grown at permissive and restrictive temperatures. Inclusion of the radioprotectors at respective concentrations during post irradiation incubation showed increase in survival of cells. Activity of DNA polymerase enzyme (yPol II) was increased significantly in cdc mutant cells exposed to gamma-radiation. Following SCGE, a linear relationship was observed between doses of irradiation and the tail moments of comets. The radioprotection of the fission yeast by radioprotectors can be seen by the reduced tail moments of the yeast comets. Caffeine also exhibited its radio-protective ability in radio-resistant S-phase cells obtained after HU treatment. Conclusions: The radioprotectors offered notable radioprotection in cdc mutants when added during irradiation. The present study showed activation of DNA damage repair enzyme (yPol II) and an increase in survival after treatment of radioprotectors in gamma irradiated wild type and cdc mutants of S. pombe cells. Results presented here showed feasibility of applying SCGE in fission yeast to follow DNA damage and radioprotection at high doses, which are not feasible with other eukaryotes. Inclusion of caffeine at 1mM concentration to S phase cells offered protection and did not decrease the cell viability. It can be proved that at minimal concentration, caffeine offered marked radioprotection.

Keywords: radiation protection, cell cycle, fission yeast, comet assay, s-phase, DNA repair, radioprotectors, caffeine, curcumin, SCGE

Procedia PDF Downloads 79

Authors: Dhanuj M. Gandikota

Abstract:

Sensor-derived three-dimensional (3D) point clouds of trees are invaluable in remote sensing analysis for the accurate measurement of key structural metrics, bio-inventory values, spatial planning/visualization, and ecological modeling. Machine learning (ML) holds the potential in addressing the restrictive tradeoffs in cost, spatial coverage, resolution, and information gain that exist in current point cloud sensing methods. Terrestrial laser scanning (TLS) remains the highest fidelity source of both canopy and below-canopy structural features, but usage is limited in both coverage and cost, requiring manual deployment to map out large, forested areas. While aerial laser scanning (ALS) remains a reliable avenue of LIDAR active remote sensing, ALS is also cost-restrictive in deployment methods. Space-borne photogrammetry from high-resolution satellite constellations is an avenue of passive remote sensing with promising viability in research for the accurate construction of vegetation 3-D point clouds. It provides both the lowest comparative cost and the largest spatial coverage across remote sensing methods. However, both space-borne photogrammetry and ALS demonstrate technical limitations in the capture of valuable below-canopy point cloud data. Looking to minimize these tradeoffs, we explored a class of powerful ML algorithms called Deep Learning (DL) that show promise in recent research on 3-D point cloud reconstruction and interpolation. Our research details the efficacy of applying these DL techniques to reconstruct accurate below-canopy point clouds from space-borne and aerial remote sensing through learned patterns of tree species fractal symmetry properties and the supplementation of locally sourced bio-inventory metrics. From our dataset, consisting of tree point clouds obtained from TLS, we deconstructed the point clouds of each tree into those that would be obtained through ALS and satellite photogrammetry of varying resolutions. We fed this ALS/satellite point cloud dataset, along with the simulated local bio-inventory metrics, into the DL point cloud reconstruction architectures to generate the full 3-D tree point clouds (the truth values are denoted by the full TLS tree point clouds containing the below-canopy information). Point cloud reconstruction accuracy was validated both through the measurement of error from the original TLS point clouds as well as the error of extraction of key structural metrics, such as crown base height, diameter above root crown, and leaf/wood volume. The results of this research additionally demonstrate the supplemental performance gain of using minimum locally sourced bio-inventory metric information as an input in ML systems to reach specified accuracy thresholds of tree point cloud reconstruction. This research provides insight into methods for the rapid, cost-effective, and accurate construction of below-canopy tree 3-D point clouds, as well as the supported potential of ML and DL to learn complex, unmodeled patterns of fractal tree growth symmetry.

Keywords: deep learning, machine learning, satellite, photogrammetry, aerial laser scanning, terrestrial laser scanning, point cloud, fractal symmetry

Procedia PDF Downloads 68

Authors: Bissonnette Jean-François, Dossa Fabrice

Abstract:

The project focuses on analyzing the spatial and temporal evolution of mangrove forest ecosystems near the city of Douala, Cameroon, in response to increasing human and environmental pressures. The selected study area, located in the Wouri River estuary, has a unique combination of economic importance, and ecological prominence. The study included valuable insights by conducting semi-structured interviews with resource operators and local officials. The thorough analysis of socio-economic data, farmer surveys, and satellite-derived information was carried out utilizing quantitative approaches in Excel and SPSS. Simultaneously, qualitative data was subjected to rigorous classification and correlation with other sources. The use of ArcGIS and CorelDraw facilitated the visual representation of the gradual changes seen in various land cover classifications. The research reveals complex processes that characterize mangrove ecosystems on Manoka and Cape Cameroon Islands. The lack of regulations in urbanization and the continuous growth of infrastructure have led to a significant increase in land conversion, causing negative impacts on natural landscapes and forests. The repeated instances of flooding and coastal erosion have further shaped landscape alterations, fostering the proliferation of water and mudflat areas. The unregulated use of mangrove resources is a significant factor in the degradation of these ecosystems. Activities including the use of wood for smoking and fishing, together with the coastal pollution resulting from the absence of waste collection, have had a significant influence. In addition, forest operators contribute to the degradation of vegetation, hence exacerbating the harmful impact of invasive species on the ecosystem. Strategic interventions are necessary to guarantee the sustainable management of these ecosystems. The proposals include advocating for sustainable wood exploitation techniques, using appropriate techniques, along with regeneration, and enforcing rules to prevent wood overexploitation. By implementing these measures, the ecological balance can be preserved, safeguarding the long-term viability of these precious ecosystems. On a conceptual level, this paper uses the framework developed by Elinor Ostrom and her colleagues to investigate the consequences of open access resources, where local actors have not been able to enforce measures to prevent overexploitation of mangrove wood resources. Governmental authorities have demonstrated limited capacity to enforce sustainable management of wood resources and have not been able to establish effective relationships with local fishing communities and with communities involved in the purchase of wood. As a result, wood resources in the mangrove areas remain largely accessible, while authorities do not monitor wood volumes extracted nor methods of exploitation. There have only been limited and punctual attempts at forest restoration with no significant consequence on mangrove forests dynamics.

Keywords: Mangroves, forest management, governance, open access resources, Cameroon

Procedia PDF Downloads 30

Authors: Farrah Putri Salmanida, Mei-Li Wu, Rika Wahyuningtyas, Wen-Bin Chung, Hso-Chi Chaung, Ko-Tung Chang

Abstract:

Within the field of immunotherapy, oncolytic virotherapy (OVT) employs dual approaches that directly eliminate tumor cells while preserving healthy ones and indirectly reprogram the tumor microenvironment (TME) to elicit antitumor responses. Within the TME, tumor associated macrophages (TAMs) manifest characteristics akin to those of anti-inflammatory M2 macrophages, thus earning the designation of M2-like TAMs. In prior research, two antigens denoted as A1 (g6Ld10T) and A3 (ORF6L5), derived from a complete sequence of ORF5 with partial sequence of ORF6 in Porcine Reproductive and Respiratory Syndrome Virus Genotype 2 (PRRSV-2), demonstrated the capacity to repolarize M2-type porcine alveolar macrophages (PAMs) into M1 phenotypes. In this study, we sought for utilizing OVT strategies by introducing A1 or A3 on TAMs to endow them with the anti-tumor traits of M1 macrophages while retaining their capacity to target cancer cells. Upon exposing human THP-1-derived M2 macrophages to a cross-species test with 2 µg/ml of either A1 or A3 for 24 hours, real time PCR revealed that A3, but not A1, treated cells exhibited upregulated gene expressions of M1 markers (CCR7, IL-1ß, CCL2, Cox2, CD80). These cells reacted to virus-derived antigen, as evidenced by increased expression of pattern-recognition receptors TLR3, TLR7, and TLR9, subsequently providing feedback in the form of type I interferon responses like IFNAR1, IFN-ß, IRF3, IRF7, OAS1, Mx1, and ISG15. Through an MTT assay, only after 15 µg/ml of A3 treatment could the cell viability decrease, with a predicted IC50 of 16.96 µg/ml. Interestingly, A3 caused dose-dependent toxicity to a rat C6 glial cancer cell line even at doses as low as 2.5 µg/ml and reached its IC50 at 9.419 µg/ml. Using Annexin V/7AAD staining and PCR test, we deduced that a significant proportion of C6 cells were undergoing the early apoptosis phase predominantly through the intrinsic apoptosis cascade involving Bcl-2 family proteins. Following this stage, we conducted a test on A3’s repolarization ability, which revealed a significant rise in M1 gene expression markers, such as TNF, CD80, and IL-1ß, in M2-like TAMs generated in vitro from murine RAW264.7 macrophages grown with conditioned medium of 4T1 breast cancer cells. This was corroborated by the results of transcriptome analysis, which revealed that the primary subset among the top 10 to top 30 significantly upregulated differentially expressed genes (DEGs) dominantly consisted of M1 macrophages profiles, including Ccl3, Ccl4, Csf3, TNF, Bcl6b, Stc1, and Dusp2. Our findings unveiled the remarkable potential of the PRRSV-derived antigen A3 to repolarize macrophages while also being capable of selectively inducing apoptosis in cancerous cells. While further in vivo study is needed for A3, it holds promise as an adjuvant by its dual effects in cancer therapy modalities.

Keywords: cancer cell apoptosis, interferon responses, macrophage repolarization, recombinant protein

Procedia PDF Downloads 32

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 242

Authors: Melanie Redding

Abstract:

Historic widespread nitrate contamination of the Lower Yakima Valley aquifer in Washington State initiated a community-based effort to reduce nitrate concentrations to below-drinking water standards. This group commissioned studies on characterizing local nitrogen sources, deep soil assessments, drinking water, and assessing nitrate concentrations at the water table. Nitrate is the most prevalent groundwater contaminant with common sources from animal and human waste, fertilizers, plants and precipitation. It is challenging to address groundwater contamination when common sources, such as agriculture, on-site sewage systems, and animal production, are widespread. Remediation is not possible, so mitigation is essential. The Lower Yakima Valley is located over 175,000 acres, with a population of 56,000 residents. Approximately 25% of the population do not have access to safe, clean drinking water, and 20% of the population is at or below the poverty level. Agriculture is the primary economic land-use activity. Irrigated agriculture and livestock production make up the largest percentage of acreage and nitrogen load. Commodities include apples, grapes, hops, dairy, silage corn, triticale, alfalfa and cherries. These commodities are important to the economic viability of the residents of the Lower Yakima Valley, as well as Washington State. Mitigation of nitrate in groundwater is challenging. The goal is to ensure everyone has safe drinking water. There are no easy remedies due to the extensive and pervasiveness of the contamination. Monitoring at the water table indicates that 45% of the 30 spatially distributed monitoring wells exceeded the drinking water standard. This indicates that there are multiple sources that are impacting water quality. Washington State has several areas which have extensive groundwater nitrate contamination. The groundwater in these areas continues to degrade over time. However, the Lower Yakima Valley is being successful in addressing this health issue because of the following reasons: the community is engaged and committed; there is one common goal; there has been extensive public education and outreach to citizens; and generating credible data using sound scientific methods. Work in this area is continuing as an ambient groundwater monitoring network is established to assess the condition of the aquifer over time. Nitrate samples are being collected from 170 wells, spatially distributed across the aquifer. This research entails quarterly sampling for two years to characterize seasonal variability and then continue annually afterward. This assessment will provide the data to statistically determine trends in nitrate concentrations across the aquifer, over time. Thirty-three of these wells are monitoring wells that are screened across the aquifer. The water quality from these wells are indicative of activities at the land surface. Additional work is being conducted to identify land use management practices that are effective in limiting nitrate migration through the soil column. Tracking nitrate in the soil column every season is an important component of bridging land-use practices with the fate and transport of nitrate through the subsurface. Patience, tenacity, and the ability to think outside the box are essential for dealing with widespread nitrate contamination of groundwater.

Keywords: community, groundwater, monitoring, nitrate

Procedia PDF Downloads 151

Authors: O. D. Ohijeagbon, Oluseyi O. Ajayi, M. Ogbonnaya, Ahmeh Attabo

Abstract:

This study analyzed the electricity generation potential from wind at seven sites spread across seven states of the North-Central region of Nigeria. Twenty-one years (1987 to 2007) wind speed data at a height of 10m were assessed from the Nigeria Meteorological Department, Oshodi. The data were subjected to different statistical tests and also compared with the two-parameter Weibull probability density function. The outcome shows that the monthly average wind speeds ranged between 2.2 m/s in November for Bida and 10.1 m/s in December for Jos. The yearly average ranged between 2.1m/s in 1987 for Bida and 11.8 m/s in 2002 for Jos. Also, the power density for each site was determined to range between 29.66 W/m2 for Bida and 864.96 W/m2 for Jos, Two parameters (k and c) of the Weibull distribution were found to range between 2.3 in Lokoja and 6.5 in Jos for k, while c ranged between 2.9 in Bida and 9.9m/s in Jos. These outcomes points to the fact that wind speeds at Jos, Minna, Ilorin, Makurdi and Abuja are compatible with the cut-in speeds of modern wind turbines and hence, may be economically feasible for wind-to-electricity at and above the height of 10 m. The study further assessed the potential and economic viability of standalone wind generation systems for off-grid rural communities located in each of the studied sites. A specific electric load profile was developed to suite hypothetic communities, each consisting of 200 homes, a school and a community health center. Assessment of the design that will optimally meet the daily load demand with a loss of load probability (LOLP) of 0.01 was performed, considering 2 stand-alone applications of wind and diesel. The diesel standalone system (DSS) was taken as the basis of comparison since the experimental locations have no connection to a distribution network. The HOMER® software optimizing tool was utilized to determine the optimal combination of system components that will yield the lowest life cycle cost. Sequel to the analysis for rural community utilization, a Distributed Generation (DG) analysis that considered the possibility of generating wind power in the MW range in order to take advantage of Nigeria’s tariff regime for embedded generation was carried out for each site. The DG design incorporated each community of 200 homes, freely catered for and offset from the excess electrical energy generated above the minimum requirement for sales to a nearby distribution grid. Wind DG systems were found suitable and viable in producing environmentally friendly energy in terms of life cycle cost and levelised value of producing energy at Jos ($0.14/kWh), Minna ($0.12/kWh), Ilorin ($0.09/kWh), Makurdi ($0.09/kWh), and Abuja ($0.04/kWh) at a particluar turbine hub height. These outputs reveal the value retrievable from the project after breakeven point as a function of energy consumed Based on the results, the study demonstrated that including renewable energy in the rural development plan will enhance fast upgrade of the rural communities.

Keywords: wind speed, wind power, distributed generation, cost per kilowatt-hour, clean energy, North-Central Nigeria

Procedia PDF Downloads 486