Search results for: digital tools and urban development

Authors: Pallab Datta, Jyotirmoy Chatterjee, Santanu Dhara

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Over the past few years, phosphorous containing polymers have received widespread attention for applications such as high performance optical fibers, flame retardant materials, drug delivery and tissue engineering. Being pentavalent, phosphorous can exist in different chemical environments in these polymers which increase their versatility. In human biochemistry, phosphorous based compounds exert their functions both in soluble and insoluble form occurring as inorganic or as organophosphorous compounds. Specifically in case of biomacromolecules, phosphates are critical for functions of DNA, ATP, phosphoproteins, phospholipids, phosphoglycans and several coenzymes. Inspired by the role of phosphorous in functional biomacromolecules, design and synthesis of biomimetic materials are thus carried out by several authors to study macromolecular function or as substitutes in clinical tissue regeneration conditions. In addition, many regulatory signals of the body are controlled by phoshphorylation of key proteins present either in form of growth factors or matrix-bound scaffold proteins. This inspires works on synthesis of phospho-peptidomimetic amino acids for understanding key signaling pathways and this is extended to obtain molecules with potentially useful biological properties. Apart from above applications, phosphate groups bound to polymer backbones have also been demonstrated to improve function of osteoblast cells and augment performance of bone grafts. Despite the advantages of phosphate grafting, however, there is limited understanding on effect of degree of phosphorylation on macromolecular physicochemical and/or biological properties. Such investigations are necessary to effectively translate knowledge of macromolecular biochemistry into relevant clinical products since they directly influence processability of these polymers into suitable scaffold structures and control subsequent biological response. Amongst various techniques for fabrication of biomimetic scaffolds, nanofibrous scaffolds fabricated by electrospinning technique offer some special advantages in resembling the attributes of natural extracellular matrix. Understanding changes in physico-chemical properties of polymers as function of phosphorylation is therefore going to be crucial in development of nanofiber scaffolds based on phosphorylated polymers. The aim of the present work is to investigate the effect of phosphorous grafting on the electrospinning behavior of polymers with aim to obtain biomaterials for bone regeneration applications. For this purpose, phosphorylated derivatives of two polymers of widely different electrospinning behaviors were selected as starting materials. Poly(vinyl alcohol) is a conveniently electrospinnable polymer at different conditions and concentrations. On the other hand, electrospinning of chitosan backbone based polymers have been viewed as a critical challenge. The phosphorylated derivatives of these polymers were synthesized, characterized and electrospinning behavior of various solutions containing these derivatives was compared with electrospinning of pure poly (vinyl alcohol). In PVA, phosphorylation adversely impacted electrospinnability while in NMPC, higher phosphate content widened concentration range for nanofiber formation. Culture of MG-63 cells on electrospun nanofibers, revealed that degree of phosphate modification of a polymer significantly improves cell adhesion or osteoblast function of cultured cells. It is concluded that improvement of cell response parameters of nanofiber scaffolds can be attained as a function of controlled degree of phosphate grafting in polymeric biomaterials with implications for bone tissue engineering applications.

Keywords: bone regeneration, chitosan, electrospinning, phosphorylation

Procedia PDF Downloads 203

Authors: Keshari Shrestha, Philip Vatterott

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Introduction: Drug reaction with eosinophilia and systemic symptoms (DRESS) syndrome is a rare and potentially fatal drug-related syndrome. DRESS classically presents with a diffuse maculopapular rash, fevers, and eosinophilia more than three weeks after drug exposure. DRESS can present with multi-organ involvement, with liver damage being the most common and severe. Pulmonary involvement is a less common manifestation and is associated with poor clinical outcomes. Chest imaging is often nonspecific, and symptoms can range from mild cough to acute respiratory distress syndrome (ARDS) . This is a case of a 49-year-old female with a history of recent clostridium difficile colitis status post treatment with oral vancomycin who presented with rash, acute liver and kidney failure, as well as diffuse nodular alveolar lung opacities concerning for DRESS syndrome with multi-organ involvement. Clinical Course: This patient initially presented to an outside hospital with clostridium difficile colitis, acute liver injury, and acute kidney injury. She developed a desquamating maculopapular rash in the setting of recent oral vancomycin, meloxicam, and furosemide initiation. She was hospitalized on two additional occasions with worsening altered mental status, liver injury, and acute kidney injury and was initiated on intermittent hemodialysis. Notably, she was found to have systemic eosinophilia (4100 cells/microliter) several weeks prior. She was transferred to this institution for further management where she was found to have encephalopathy, jaundice, lower extremity edema, and diffuse bilateral rhonchorous breath sounds on pulmonary examination. The patient was started on methylprednisolone for suspected DRESS syndrome. She underwent an evaluation for alternative causes of her organ failure. Her workup included a negative infectious, autoimmune, metabolic, toxic, and malignant work-up. Abdominal computed tomography (CT) and ultrasound were remarkable for evidence of hepatic steatosis and possible cirrhotic morphology. Additionally, a chest CT demonstrated diffuse and symmetric nodular alveolar lung opacities with peripheral sparing not consistent with acute respiratory distress syndrome or edema. Ultimately, her condition continued to decline, and she required intubation on several occasions. On hospital day 25 she succumbed to distributive shock in the setting of probable sepsis and multi-organ failure. Discussion: DRESS syndrome occurs in 1 in 1,000 to 10,000 patients with a mortality rate of around 10%. Anti-convulsant, anti-bacterial, anti-viral, and sulfonamide drugs are the most common drugs implicated in the development of DRESS syndrome; however, the list of offending agents is extensive . The diagnosis of DRESS syndrome is made after excluding other causes of disease such as infectious and autoimmune etiologies. The RegiSCAR scoring system is used to diagnose DRESS syndrome with 2-3 points indicating possible disease, 4-5 probable disease, and >5 definite disease. This patient scored a 7 on the RegiSCAR scale for eosinophilia, rash, organ involvement, and exclusion of other causes (infectious and autoimmune). While the pharmacologic trigger in this case is unknown, it is speculated to be caused by vancomycin, meloxicam, or furosemide due to the favorable timeline of initiation. Despite aggressive treatment, DRESS syndrome can often be fatal. Because of this, early diagnosis and treatment of patients with suspected DRESS syndrome is imperative.

Keywords: drug reaction with eosinophilia and systemic symptoms, multi-organ failure, pulmonary involvement, renal failure

Procedia PDF Downloads 153

Authors: Michael R. Shurin, Galina Shurin, Vladimir A. Kirichenko

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Background. Visibility of hepatic malignancies is poor on non-contrast imaging for daily verification of liver malignancies prior to radiation therapy on MRI-guided Linear Accelerators (MR-Linac). Ferumoxytol® (Feraheme, AMAG Pharmaceuticals, Waltham, MA) is a SPION agent that is increasingly utilized off-label as hepatic MRI contrast. This agent has the advantage of providing a functional assessment of the liver based upon its uptake by hepatic Kupffer cells proportionate to vascular perfusion, resulting in strong T1, T2 and T2* relaxation effects and enhanced contrast of malignant tumors, which lack Kupffer cells. The latter characteristic has been recently utilized for MRI-guided radiotherapy planning with precision targeting of liver malignancies. However potential radiotoxicity of SPION has never been addressed for its safe use as an MRI-contrast agent during liver radiotherapy on MRI-Linac. This study defines the radiomodulating properties of SPIONs in vitro on human monocyte and macrophage cell lines exposed to 60Go gamma-rays within clinical radiotherapy dose range. Methods. Human monocyte and macrophages cell line in cultures were loaded with a clinically relevant concentration of Ferumoxytol (30µg/ml) for 2 and 24 h and irradiated to 3Gy, 5Gy and 10Gy. Cells were washed and cultured for additional 24 and 48 h prior to assessing their phenotypic activation by flow cytometry and function, including viability (Annexin V/PI assay), proliferation (MTT assay) and cytokine expression (Luminex assay). Results. Our results reveled that SPION affected both human monocytes and macrophages in vitro. Specifically, iron oxide nanoparticles decreased radiation-induced apoptosis and prevented radiation-induced inhibition of human monocyte proliferative activity. Furthermore, Ferumoxytol protected monocytes from radiation-induced modulation of phenotype. For instance, while irradiation decreased polarization of monocytes to CD11b+CD14+ and CD11bnegCD14neg phenotype, Ferumoxytol prevented these effects. In macrophages, Ferumoxytol counteracted the ability of radiation to up-regulate cell polarization to CD11b+CD14+ phenotype and prevented radiation-induced down-regulation of expression of HLA-DR and CD86 molecules. Finally, Ferumoxytol uptake by human monocytes down-regulated expression of pro-inflammatory chemokines MIP-1α (Macrophage inflammatory protein 1α), MIP-1β (CCL4) and RANTES (CCL5). In macrophages, Ferumoxytol reversed the expression of IL-1RA, IL-8, IP-10 (CXCL10) and TNF-α, and up-regulates expression of MCP-1 (CCL2) and MIP-1α in irradiated macrophages. Conclusion. SPION agent Ferumoxytol increases resistance of human monocytes to radiation-induced cell death in vitro and supports anti-inflammatory phenotype of human macrophages under radiation. The effect is radiation dose-dependent and depends on the duration of Feraheme uptake. This study also finds strong evidence that SPIONs reversed the effect of radiation on the expression of pro-inflammatory cytokines involved in initiation and development of radiation-induced liver damage. Correlative translational work at our institution will directly assess the cyto-protective effects of Ferumoxytol on human Kupfer cells in vitro and ex vivo analysis of explanted liver specimens in a subset of patients receiving Feraheme-enhanced MRI-guided radiotherapy to the primary liver tumors as a bridge to liver transplant.

Keywords: superparamagnetic iron oxide nanoparticles, radioprotection, magnetic resonance imaging, liver

Procedia PDF Downloads 56

Authors: Michelle C. S. Azevedo, Priscila M. Colavite, Carolina F. Francisconi, Ana P. Trombone, Gustavo P. Garlet

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VIP (vasoactive intestinal peptide) know as a potential protective factor in the view of its marked immunosuppressive properties. In this work, we investigated a possible association of VIP with the clinical status of experimental periapical granulomas and the association with expression markers in the lesions potentially associated with periapical lesions pathogenesis. C57BL/6WT mice were treated or not with recombinant VIP. Animals with active/progressive (N=40), inactive/stable (N=70) periapical granulomas and controls (N=50) were anesthetized and the right mandibular first molar was surgically opened, allowing exposure of dental pulp. Endodontic pathogenic bacterial strains were inoculated: Porphyromonas gingivalis, Prevotella nigrescens, Actinomyces viscosus, and Fusobacterium nucleatum subsp. polymorphum. The cavity was not sealed after bacterial inoculation. During lesion development, animals were treated or not with recombinant VIP 3 days post infection. Animals were killed after 3, 7, 14, and 21 days of infection and the jaws were dissected. The extraction of total RNA from periodontal tissues was performed and the integrity of samples was checked. qPCR reaction using TaqMan chemistry with inventoried primers were performed in ViiA7 equipment. The results, depicted as the relative levels of gene expression, were calculated in reference to GAPDH and β-actin expression. Periodontal tissues from upper molars were vested and incubated supplemented RPMI, followed by processing with 0.05% DNase. Cell viability and couting were determined by Neubauer chamber analysis. For flow cytometry analysis, after cell counting the cells were stained with the optimal dilution of each antibody; (PE)-conjugated and (FITC)-conjugated antibodies against CD4, CD25, FOXP3, IL-4, IL-17 and IFN-γ antibodies, as well their respective isotype controls. Cells were analyzed by FACScan and CellQuest software. Results are presented as the number of cells in the periodontal tissues or the number of positive cells for each marker in the CD4+FOXp3+, CD4+IL-4+, CD4+IFNg+ and CD4+IL-17+ subpopulations. The levels mRNA were measured by qPCR. The VIP expression was predominated in inactive lesions, as well part of the clusters of cytokine/Th markers identified as protective factors and a negative correlation between VIP expression and lesion evolution was observed. A quantitative analysis of IL1β, IL17, TNF, IFN, MMP2, RANKL, OPG, IL10, TGFβ, CTLA4, COL5A1, CTGF, CXCL11, FGF7, ITGA4, ITGA5, SERP1 and VTN expression was measured in experimental periapical lesions treated with VIP 7 and 14 days after lesion induction and healthy animals. After 7 days, all targets presented a significate increase in comparison to untreated animals. About migration kinetics, profile of chemokine receptors expression of TCD4+ subsets and phenotypic analysis of Tregs, Th1, Th2 and Th17 cells during the course of experimental periodontal disease evaluated by flow cytometry and depicted as the number of positive cells for each marker. CD4+IFNg+ and CD4+FOXp3+ cells migration were significate increased 7 days post VIP treatment. CD4+IL17+ cells migration were significate increased 7 and 14 days post VIP treatment, CD4+IL4+ cells migration were significate increased 14 and 21 days post VIP treatment compared to the control group. In conclusion, our experimental data support VIP involvement in determining the inactivity of periapical lesions. Financial support: FAPESP #2015/25618-2.

Keywords: chronic inflammation, cytokines, osteolytic lesions, VIP (Vasoactive Intestinal Peptide)

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Authors: Daniel Stabler, Anne-Laure Mention, Henri Hakala, Ahmad Alaassar

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In Europe, 2.2 billion tons of waste annually generate severe environmental damage and economic burdens, and negatively impact human health. A stark illustration of the problem is found within the consumer electronics industry, which reflects one of the most complex global waste streams. Of the 5.3 billion globally discarded mobile phones in 2022, only 17% were properly recycled. To address these pressing issues, Europe has made significant strides in developing waste management strategies, Circular Economy initiatives, and Right to Repair policies. These endeavors aim to make product repair and maintenance more accessible, extend product lifespans, reduce waste, and promote sustainable resource use. European countries have introduced Right to Repair policies, often in conjunction with extended producer responsibility legislation, repair subsidies, and consumer repair indices, to varying degrees of regulatory rigor. Changing societal trends emphasizing sustainability and environmental responsibility have driven consumer demand for more sustainable and repairable products, benefiting repair-focused consumer electronics businesses. In academic research, much of the literature in Management studies has examined the European Circular Economy and the Right to Repair from firm-level perspectives. These studies frequently employ a business-model lens, emphasizing innovation and strategy frameworks. However, this study takes an institutional perspective, aiming to understand the adoption of Circular Economy and repair-focused business models within the European consumer electronics market. The concepts of the Circular Economy and the Right to Repair align with institutionalism as they reflect evolving societal norms favoring sustainability and consumer empowerment. Regulatory institutions play a pivotal role in shaping and enforcing these concepts through legislation, influencing the behavior of businesses and individuals. Compliance and enforcement mechanisms are essential for their success, compelling actors to adopt sustainable practices and consider product life extension. Over time, these mechanisms create a path for more sustainable choices, underscoring the influence of institutions and societal values on behavior and decision-making. Institutionalism, particularly 'neo-institutionalism,' provides valuable insights into the factors driving the adoption of Circular and repair-focused business models. Neo-institutional pressures can manifest through coercive regulatory initiatives or normative standards shaped by socio-cultural trends. The Right to Repair movement has emerged as a prominent and influential idea within academic discourse and sustainable development initiatives. Therefore, understanding how macro-level societal shifts toward the Circular Economy and the Right to Repair trigger firm-level responses is imperative. This study aims to answer a crucial question about the impact of European Right to Repair initiatives had on the financial and environmental performance of European consumer electronics companies at the firm level. A quantitative and statistical research design will be employed. The study will encompass an extensive sample of consumer electronics firms in Northern and Western Europe, analyzing their financial and environmental performance in relation to the implementation of Right to Repair mechanisms. The study's findings are expected to provide valuable insights into the broader implications of the Right to Repair and Circular Economy initiatives on the European consumer electronics industry.

Keywords: circular economy, right to repair, institutionalism, environmental management, european union

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Authors: Eunjung Lee

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This research investigates the intricate connection between cultural differences and online consumer behaviors by integrating Hofstede's Cultural Dimensions theory with analysis methodologies such as text mining, data mining, and topic analysis. Our aim is to provide a comprehensive understanding of how national cultural differences influence individuals' behaviors when engaging with online reviews. To ensure the relevance of our investigation, we systematically analyze and interpret the cultural nuances influencing online consumer behaviors, especially in the context of online reviews. By anchoring our research in Hofstede's Cultural Dimensions theory, we seek to offer valuable insights for marketers to tailor their strategies based on the cultural preferences of diverse global consumer bases. In our methodology, we employ advanced text mining techniques to extract insights from a diverse range of online reviews gathered globally for a specific product or service like Netflix. This approach allows us to reveal hidden cultural cues in the language used by consumers from various backgrounds. Complementing text mining, data mining techniques are applied to extract meaningful patterns from online review datasets collected from different countries, aiming to unveil underlying structures and gain a deeper understanding of the impact of cultural differences on online consumer behaviors. The study also integrates topic analysis to identify recurring subjects, sentiments, and opinions within online reviews. Marketers can leverage these insights to inform the development of culturally sensitive strategies, enhance target audience segmentation, and refine messaging approaches aligned with cultural preferences. Anchored in Hofstede's Cultural Dimensions theory, our research employs sophisticated methodologies to delve into the intricate relationship between cultural differences and online consumer behaviors. Applied to specific cultural dimensions, such as individualism vs. collectivism, masculinity vs. femininity, uncertainty avoidance, and long-term vs. short-term orientation, the study uncovers nuanced insights. For example, in exploring individualism vs. collectivism, we examine how reviewers from individualistic cultures prioritize personal experiences while those from collectivistic cultures emphasize communal opinions. Similarly, within masculinity vs. femininity, we investigate whether distinct topics align with cultural notions, such as robust features in masculine cultures and user-friendliness in feminine cultures. Examining information-seeking behaviors under uncertainty avoidance reveals how cultures differ in seeking detailed information or providing succinct reviews based on their comfort with ambiguity. Additionally, in assessing long-term vs. short-term orientation, the research explores how cultural focus on enduring benefits or immediate gratification influences reviews. These concrete examples contribute to the theoretical enhancement of Hofstede's Cultural Dimensions theory, providing a detailed understanding of cultural impacts on online consumer behaviors. As online reviews become increasingly crucial in decision-making, this research not only contributes to the academic understanding of cultural influences but also proposes practical recommendations for enhancing online review systems. Marketers can leverage these findings to design targeted and culturally relevant strategies, ultimately enhancing their global marketing effectiveness and optimizing online review systems for maximum impact.

Keywords: comparative analysis, cultural dimensions, marketing intelligence, national culture, online consumer behavior, text mining

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Authors: Inna Kornienko, Svetlana Guryeva, Natalia Danilova, Elena Petersen

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Drug toxicity often goes undetected until clinical trials, the most expensive and dangerous phase of drug development. Both human cell culture and animal studies have limitations that cannot be overcome by improvements in drug testing protocols. Tissue engineering is an emerging alternative approach to creating models of human malignant tumors for experimental oncology, personalized medicine, and drug discovery studies. This new generation of bioengineered tumors provides an opportunity to control and explore the role of every component of the model system including cell populations, supportive scaffolds, and signaling molecules. An area that could greatly benefit from these models is cancer research. Recent advances in tissue engineering demonstrated that decellularized tissue is an excellent scaffold for tissue engineering. Decellularization of donor organs such as heart, liver, and lung can provide an acellular, naturally occurring three-dimensional biologic scaffold material that can then be seeded with selected cell populations. Preliminary studies in animal models have provided encouraging results for the proof of concept. Decellularized Organs preserve organ microenvironment, which is critical for cancer metastasis. Utilizing 3D tumor models results greater proximity of cell culture morphological characteristics in a model to its in vivo counterpart, allows more accurate simulation of the processes within a functioning tumor and its pathogenesis. 3D models allow study of migration processes and cell proliferation with higher reliability as well. Moreover, cancer cells in a 3D model bear closer resemblance to living conditions in terms of gene expression, cell surface receptor expression, and signaling. 2D cell monolayers do not provide the geometrical and mechanical cues of tissues in vivo and are, therefore, not suitable to accurately predict the responses of living organisms. 3D models can provide several levels of complexity from simple monocultures of cancer cell lines in liquid environment comprised of oxygen and nutrient gradients and cell-cell interaction to more advanced models, which include co-culturing with other cell types, such as endothelial and immune cells. Following this reasoning, spheroids cultivated from one or multiple patient-derived cell lines can be utilized to seed the matrix rather than monolayer cells. This approach furthers the progress towards personalized medicine. As an initial step to create a new ex vivo tissue engineered model of a cancer tumor, optimized protocols have been designed to obtain organ-specific acellular matrices and evaluate their potential as tissue engineered scaffolds for cultures of normal and tumor cells. Decellularized biomatrix was prepared from animals’ kidneys, urethra, lungs, heart, and liver by two decellularization methods: perfusion in a bioreactor system and immersion-agitation on an orbital shaker with the use of various detergents (SDS, Triton X-100) in different concentrations and freezing. Acellular scaffolds and tissue engineered constructs have been characterized and compared using morphological methods. Models using decellularized matrix have certain advantages, such as maintaining native extracellular matrix properties and biomimetic microenvironment for cancer cells; compatibility with multiple cell types for cell culture and drug screening; utilization to culture patient-derived cells in vitro to evaluate different anticancer therapeutics for developing personalized medicines.

Keywords: 3D models, decellularization, drug discovery, drug toxicity, scaffolds, spheroids, tissue engineering

Procedia PDF Downloads 281

Authors: Adela Diepoltova, Klara Konecna, Ondrej Jandourek, Petr Nachtigal

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A loss of control over antibiotic-resistant pathogens has become a global issue due to severe and often untreatable infections. This state is reflected in complicated treatment, health costs, and higher mortality. All these factors emphasize the urgent need for the discovery and development of new anti-infectives. One of the most common pathogens mentioned in the phenomenon of antibiotic resistance are bacteria of the genus Staphylococcus. These bacterial agents have developed several mechanisms against the effect of antibiotics. One of them is biofilm formation. In staphylococci, biofilms are associated with infections such as endocarditis, osteomyelitis, catheter-related bloodstream infections, etc. To author's best knowledge, no validated and standardized methodology evaluating candidate compound activity against staphylococcal biofilms exists. However, a variety of protocols for in vitro drug activity testing has been suggested, yet there are often fundamental differences. Based on our experience, a key methodological step that leads to credible results is to form a robust biofilm with appropriate attributes such as firm adherence to the substrate, a complex arrangement in layers, and the presence of extracellular polysaccharide matrix. At first, for the purpose of drug antibiofilm activity evaluation, the focus was put on various conditions (supplementation of cultivation media by human plasma/fetal bovine serum, shaking mode, the density of initial inoculum) that should lead to reproducible and robust in vitro staphylococcal biofilm formation in microtiter plate model. Three model staphylococcal reference strains were included in the study: Staphylococcus aureus (ATCC 29213), methicillin-resistant Staphylococcus aureus (ATCC 43300), and Staphylococcus epidermidis (ATCC 35983). The total biofilm biomass was quantified using the Christensen method with crystal violet, and results obtained from at least three independent experiments were statistically processed. Attention was also paid to the viability of the biofilm-forming staphylococcal cells and the presence of extracellular polysaccharide matrix. The conditions that led to robust biofilm biomass formation with attributes for biofilms mentioned above were then applied by introducing an alternative method analogous to the commercially available test system, the Calgary Biofilm Device. In this test system, biofilms are formed on pegs that are incorporated into the lid of the microtiter plate. This system provides several advantages (in situ detection and quantification of biofilm microbial cells that have retained their viability after drug exposure). Based on our preliminary studies, it was found that the attention to the peg surface and substrate on which the bacterial biofilms are formed should also be paid to. Therefore, further steps leading to the optimization were introduced. The surface of pegs was coated by human plasma, fetal bovine serum, and L-polylysine. Subsequently, the willingness of bacteria to adhere and form biofilm was monitored. In conclusion, suitable conditions were revealed, leading to the formation of reproducible, robust staphylococcal biofilms in vitro for the microtiter model and the system analogous to the Calgary biofilm device, as well. The robustness and typical slime texture could be detected visually. Likewise, an analysis by confocal laser scanning microscopy revealed a complex three-dimensional arrangement of biofilm forming organisms surrounded by an extracellular polysaccharide matrix.

Keywords: anti-biofilm drug activity screening, in vitro biofilm formation, microtiter plate model, the Calgary biofilm device, staphylococcal infections, substrate modification, surface coating

Procedia PDF Downloads 138

Authors: Ipsita Pujari, Abitha Thomas, Vidhu S. Babu, K. Satyamoorthy

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Orchids are esteemed as celebrities in cut flower industry globally, due to their long-lasting fragrance and freshness. Apart from splendor, the unique metabolites endowed with pharmaceutical potency have made them one of the most hunted in plant kingdom. This had led to their trafficking, resulting in habitat loss, subsequently making them occupiers of IUCN red list as RET species. Many of the orchids especially wild varieties still remain undiscovered. In view to protect and conserve the wild germplasm, researchers have been inventing novel micropropagation protocols; thereby conserving Orchids. India is overflowing with exclusive wild cultivars of Orchids, whose pharmaceutical properties remain untapped and are not marketed owing to relatively small flowers. However, their germplasm is quite pertinent to be preserved for making unusual hybrids. Dendrobium genus is the second largest among Orchids exists in India and has highest demand attributable to enduring cut flowers and significant therapeutic uses in traditional medicinal system. Though the genus is quite endemic in Western Ghat regions of the country, many species are still anonymous with their unknown curative properties. A standard breeding cycle in Orchids usually takes five to seven years (Dendrobium hybrids taking a long juvenile phase of two to five years reaching maturity and flowering stage) and this extensive life cycle has always hindered the development of Dendrobium breeding. Dendrobium is reported with essential therapeutic plant bio-chemicals and ‘Moscatilin’ is one, found exclusive to this famous Dendrobium genus. Moscatilin is reported to have anti-mutagenic and anti-cancer properties, whose positive action has very recently been demonstrated against a range of cancers. Our preliminary study here established a simple and economic small-scale propagation protocol of Dendrobium ovatum describing in vitro production of Moscatilin. Subsequently for enhancing the content of Moscatilin, an efficient experimental related to the organization of transgenic (hairy) D. ovatum root cultures through infection of Agrobacterium rhizogenes 2364 strain on MS basal medium is being reported in the present study. Hairy roots generated on almost half of the explants used (spherules, in vitro plantlets and calli) maintained through suspension cultures, after 8 weeks of co-cultivation with Agrobacterium rhizogenes. GFP assay performed with isolated hairy roots has confirmed the integrative transformation which was further positively confirmed by PCR using rolB gene specific primers. Reverse phase-high performance liquid chromatography and mass spectrometry techniques were used for quantification and accurate identification of Moscatilin respectively from transgenic systems. A noticeable ~3 fold increase in contents were observed in transformed D. ovatum root cultures as compared to the simple in vitro culture, callus culture and callus regeneration plantlets. Role of elicitors e.g., Methyl jasmonate, Salicylic acid, Yeast extract and Chitosan were tested for elevating the Moscatilin content to obtain a comprehensive optimized protocol facilitating the in vitro production of valuable Moscatilin with larger yield. This study would provide evidence towards the in vitro assembly of Moscatilin within a short time-period through not a so-expensive technology for the first time. It also serves as an appropriate basis for bioreactor scale-up resulting in commercial bioproduction of Moscatilin.

Keywords: bioproduction, Dendrobium ovatum, hairy root culture, moscatilin

Procedia PDF Downloads 218

Authors: Pei Yi Lin

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Objective: The objective of this study is to use machine learning methods to build an early prediction classifier model for acute delirium to improve the quality of medical care for intensive care patients. Background: Delirium is a common acute and sudden disturbance of consciousness in critically ill patients. After the occurrence, it is easy to prolong the length of hospital stay and increase medical costs and mortality. In 2021, the incidence of delirium in the intensive care unit of internal medicine was as high as 59.78%, which indirectly prolonged the average length of hospital stay by 8.28 days, and the mortality rate is about 2.22% in the past three years. Therefore, it is expected to build a delirium prediction classifier through big data analysis and machine learning methods to detect delirium early. Method: This study is a retrospective study, using the artificial intelligence big data database to extract the characteristic factors related to delirium in intensive care unit patients and let the machine learn. The study included patients aged over 20 years old who were admitted to the intensive care unit between May 1, 2022, and December 31, 2022, excluding GCS assessment <4 points, admission to ICU for less than 24 hours, and CAM-ICU evaluation. The CAMICU delirium assessment results every 8 hours within 30 days of hospitalization are regarded as an event, and the cumulative data from ICU admission to the prediction time point are extracted to predict the possibility of delirium occurring in the next 8 hours, and collect a total of 63,754 research case data, extract 12 feature selections to train the model, including age, sex, average ICU stay hours, visual and auditory abnormalities, RASS assessment score, APACHE-II Score score, number of invasive catheters indwelling, restraint and sedative and hypnotic drugs. Through feature data cleaning, processing and KNN interpolation method supplementation, a total of 54595 research case events were extracted to provide machine learning model analysis, using the research events from May 01 to November 30, 2022, as the model training data, 80% of which is the training set for model training, and 20% for the internal verification of the verification set, and then from December 01 to December 2022 The CU research event on the 31st is an external verification set data, and finally the model inference and performance evaluation are performed, and then the model has trained again by adjusting the model parameters. Results: In this study, XG Boost, Random Forest, Logistic Regression, and Decision Tree were used to analyze and compare four machine learning models. The average accuracy rate of internal verification was highest in Random Forest (AUC=0.86), and the average accuracy rate of external verification was in Random Forest and XG Boost was the highest, AUC was 0.86, and the average accuracy of cross-validation was the highest in Random Forest (ACC=0.77). Conclusion: Clinically, medical staff usually conduct CAM-ICU assessments at the bedside of critically ill patients in clinical practice, but there is a lack of machine learning classification methods to assist ICU patients in real-time assessment, resulting in the inability to provide more objective and continuous monitoring data to assist Clinical staff can more accurately identify and predict the occurrence of delirium in patients. It is hoped that the development and construction of predictive models through machine learning can predict delirium early and immediately, make clinical decisions at the best time, and cooperate with PADIS delirium care measures to provide individualized non-drug interventional care measures to maintain patient safety, and then Improve the quality of care.

Keywords: critically ill patients, machine learning methods, delirium prediction, classifier model

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Authors: Patricia Shirley Almeida Prado, Selma Paixão Argollo, Maria De Fátima Teixeira Guimarães, Leticia Matos Sobrinho

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Skeletal differential diagnosis is essential in forensic anthropology in order to differentiate skeletal trauma from normal osseous variation and pathological processes. Thus, part of forensic anthropological field is differentiate skeletal criminal injuries from the normal skeletal variation (bone fusion or nonunion, transitional vertebrae and other non-metric traits), non-traumatic skeletal pathology (myositis ossificans, arthritis, bone metastasis, osteomyelitis) from traumatic skeletal pathology (myositis ossificans traumatic) avoiding misdiagnosis. This case shows the importance of effective pathological diagnosis in order to accelerate the identification process of skeletonized human remains. THE CASE: An unidentified skeletal remains at the medico legal institute Nina Rodrigues-Salvador, of a male young adult (29 to 40 years estimated) showing a massive heterotopic ossification on its right tibia at upper epiphysis and adjacent articular femur surface; an extensive ossification on the right clavicle (at the sternal extremity) also presenting an heterotopic ossification at right scapulae (upper third of scapulae lateral margin and infraglenoid tubercule) and at the head of right humerus at the shoulder joint area. Curiously, this case also shows an unusual porosity in certain vertebrae´s body and in some tarsal and carpal bones. Likewise, his left fifth metacarpal bones (right and left) showed a healed fracture which led both bones distorted. Based on identification, of pathological conditions in human skeletal remains literature and protocols these alterations can be misdiagnosed and this skeleton may present more than one pathological process. The anthropological forensic lab at Medico-legal Institute Nina Rodrigues in Salvador (Brazil) adopts international protocols to ancestry, sex, age and stature estimations, also implemented well-established conventions to identify pathological disease and skeletal alterations. The most compatible diagnosis for this case is hematogenous osteomyelitis due to following findings: 1: the healed fracture pattern at the clavicle showing a cloaca which is a pathognomonic for osteomyelitis; 2: the metacarpals healed fracture does not present cloaca although they developed a periosteal formation. 3: the superior articular surface of the right tibia shows an extensive inflammatory healing process that extends to adjacent femur articular surface showing some cloaca at tibia bone disease. 4: the uncommon porosities may result from hematogenous infectious process. The fractures probably have occurred in a different moments based on the healing process; the tibia injury is more extensive and has not been reorganized, while metacarpals and clavicle fracture is properly healed. We suggest that the clavicle and tibia´s fractures were infected by an existing infectious disease (syphilis, tuberculosis, brucellosis) or an existing syndrome (Gorham’s disease), which led to the development of osteomyelitis. This hypothesis is supported by the fact that different bones are affected in diverse levels. Like the metacarpals that do not show the cloaca, but then a periosteal new bone formation; then the unusual porosities do not show a classical osteoarthritic processes findings as the marginal osteophyte, pitting and new bone formation, they just show an erosive process without bone formation or osteophyte. To confirm and prove our hypothesis we are working on different clinical approaches like DNA, histopathology and other image exams to find the correct diagnostic.

Keywords: bone disease, forensic anthropology, hematogenous osteomyelitis, human identification, human remains

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Authors: Zbigniew Czyz, Ksenia Siadkowska, Krzysztof Skiba, Karol Scislowski

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Today’s progress in the rotorcraft is mostly associated with an optimization of aircraft performance achieved by active and passive modifications of main rotor assemblies and a tail propeller. The key task is to improve their performance, improve the hover quality factor for rotors but not change in specific fuel consumption. One of the tasks to improve the helicopter is an active optimization of the main rotor providing for flight stages, i.e., an ascend, flight, a descend. An active interference with the airflow around the rotor blade section can significantly change characteristics of the aerodynamic airfoil. The efficiency of actuator systems modifying aerodynamic coefficients in the current solutions is relatively high and significantly affects the increase in strength. The solution to actively change aerodynamic characteristics assumes a periodic change of geometric features of blades depending on flight stages. Changing geometric parameters of blade warping enables an optimization of main rotor performance depending on helicopter flight stages. Structurally, an adaptation of shape memory alloys does not significantly affect rotor blade fatigue strength, which contributes to reduce costs associated with an adaptation of the system to the existing blades, and gains from a better performance can easily amortize such a modification and improve profitability of such a structure. In order to obtain quantitative and qualitative data to solve this research problem, a number of numerical analyses have been necessary. The main problem is a selection of design parameters of the main rotor and a preliminary optimization of its performance to improve the hover quality factor for rotors. This design concept assumes a three-bladed main rotor with a chord of 0.07 m and radius R = 1 m. The value of rotor speed is a calculated parameter of an optimization function. To specify the initial distribution of geometric warping, a special software has been created that uses a numerical method of a blade element which respects dynamic design features such as fluctuations of a blade in its joints. A number of performance analyses as a function of rotor speed, forward speed, and altitude have been performed. The calculations were carried out for the full model assembly. This approach makes it possible to observe the behavior of components and their mutual interaction resulting from the forces. The key element of each rotor is the shaft, hub and pins holding the joints and blade yokes. These components are exposed to the highest loads. As a result of the analysis, the safety factor was determined at the level of k > 1.5, which gives grounds to obtain certification for the strength of the structure. The construction of the joint rotor has numerous moving elements in its structure. Despite the high safety factor, the places with the highest stresses, where the signs of wear and tear may appear, have been indicated. The numerical analysis carried out showed that the most loaded element is the pin connecting the modular bearing of the blade yoke with the element of the horizontal oscillation joint. The stresses in this element result in a safety factor of k=1.7. The other analysed rotor components have a safety factor of more than 2 and in the case of the shaft, this factor is more than 3. However, it must be remembered that the structure is as strong as the weakest cell is. Designed rotor for unmanned aerial vehicles adapted to work with blades with intelligent materials in its structure meets the requirements for certification testing. Acknowledgement: This work has been financed by the Polish National Centre for Research and Development under the LIDER program, Grant Agreement No. LIDER/45/0177/L-9/17/NCBR/2018.

Keywords: main rotor, rotorcraft aerodynamics, shape memory alloy, materials, unmanned helicopter

Procedia PDF Downloads 132

Authors: Nur A. Özdemir, Sude Erkin, Hatice K. Güney, Cemre S. Atılgan, Enes Huylu, Hüseyin Y. Altıntaş, Aysemin Top, Özak Durmuş

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Carbon emissions produced during a product’s life cycle, from extraction of raw materials up to waste disposal and market consumption activities are the major contributors to global warming. In the light of the science-based targets (SBT) leading the way to a zero-carbon economy for sustainable growth of the companies, carbon footprint reporting of the purchased goods has become critical for identifying hotspots and best practices for emission reduction opportunities. In line with Ford Otosan's corporate sustainability strategy, research was conducted to evaluate the carbon footprint of purchased products in accordance with Scope 3 of the Greenhouse Gas Protocol (GHG). The purpose of this paper is to develop a systematic and transparent methodology to calculate carbon footprint of the products produced by automotive OEMs (Original Equipment Manufacturers) within the context of automobile supply chain management. To begin with, primary material data were collected through IMDS (International Material Database System) corresponds to company’s three distinct types of vehicles including Light Commercial Vehicle (Courier), Medium Commercial Vehicle (Transit and Transit Custom), Heavy Commercial Vehicle (F-MAX). Obtained material data was classified as metals, plastics, liquids, electronics, and others to get insights about the overall material distribution of produced vehicles and matched to the SimaPro Ecoinvent 3 database which is one of the most extent versions for modelling material data related to the product life cycle. Product life cycle analysis was calculated within the framework of ISO 14040 – 14044 standards by addressing the requirements and procedures. A comprehensive literature review and cooperation with suppliers were undertaken to identify the production methods of parts used in vehicles and to find out the amount of scrap generated during part production. Cumulative weight and material information with related production process belonging the components were listed by multiplying with current sales figures. The results of the study show a key modelling on carbon footprint of products and processes based on a scientific approach to drive sustainable growth by setting straightforward, science-based emission reduction targets. Hence, this study targets to identify the hotspots and correspondingly provide broad ideas about our understanding of how to integrate carbon footprint estimates into our company's supply chain management by defining convenient actions in line with climate science. According to emission values arising from the production phase including raw material extraction and material processing for Ford OTOSAN vehicles subjected in this study, GHG emissions from the production of metals used for HCV, MCV and LCV account for more than half of the carbon footprint of the vehicle's production. Correspondingly, aluminum and steel have the largest share among all material types and achieving carbon neutrality in the steel and aluminum industry is of great significance to the world, which will also present an immense impact on the automobile industry. Strategic product sustainability plan which includes the use of secondary materials, conversion to green energy and low-energy process design is required to reduce emissions of steel, aluminum, and plastics due to the projected increase in total volume by 2030.

Keywords: automotive, carbon footprint, IMDS, scope 3, SimaPro, sustainability

Procedia PDF Downloads 88

Authors: Roven Tumaneng, Angelica Kristina Monzon, Ralph Sedricke Lapuz, Jose Don De Alban, Jennica Paula Masigan, Joanne Rae Pales, Laila Monera Pornel, Dennis Tablazon, Rizza Karen Veridiano, Jackie Lou Wenceslao, Edmund Leo Rico, Neil Aldrin Mallari

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Most protected area management plans in the Philippines, particularly the smaller and more remote islands suffer from insufficient baseline data, which should provide the bases for formulating measureable conservation targets and appropriate management interventions for these protected areas. Attempts to synthesize available data particularly on cultural and socio-economic characteristic of local peoples within and outside protected areas also suffer from the lack of comprehensive and detailed inventories, which should be considered in designing adaptive management interventions to be used for those protected areas. Mt Guiting-guiting Natural Park (MGGNP) located in Sibuyan Island is one of the poorly studied protected areas in the Philippines. In this study, we determined the highly biologically important areas of the protected area using Maximum Entropy approach (MaxEnt) from environmental predictors (i.e., topographic, bioclimatic,land cover, and soil image layers) derived from global remotely sensed data and point occurrence data of species of birds and trees recorded during field surveys on the island. A total of 23 trigger species of birds and trees was modeled and stacked to generate species richness maps for biological high conservation value areas (HCVAs). Forest habitat change was delineated using dual-polarised L-band ALOS-PALSAR mosaic data at 25 meter spatial resolution, taken at two acquisition years 2007 and 2009 to provide information on forest cover ad habitat change in the island between year 2007 and 2009. Determining the livelihood guilds were also conducted using the data gathered from171 household interviews, from which demographic and livelihood variables were extracted (i.e., age, gender, number of household members, educational attainment, years of residency, distance from forest edge, main occupation, alternative sources of food and resources during scarcity months, and sources of these alternative resources).Using Principal Component Analysis (PCA) and Kruskal-Wallis test, the diversity and patterns of forest resource use by people in the island were determined with particular focus on the economic activities that directly and indirectly affect the population of key species as well as to identify levels of forest resource use by people in different areas of the park.Results showed that there are gaps in the area occupied by the natural park, as evidenced by the mismatch of the proposed HCVAs and the existing perimeters of the park. We found out that subsistence forest gathering was the possible main driver for forest degradation out of the eight livelihood guilds that were identified in the park. Determining the high conservation areas and identifyingthe anthropogenic factors that influence the species richness and abundance of key species in the different management zone of MGGNP would provide guidance for the design of a protected area management plan and future monitoring programs. However, through intensive communication and consultation with government stakeholders and local communities our results led to setting conservation targets in local development plans and serve as a basis for the reposition of the boundaries and reconfiguration of the management zones of MGGNP.

Keywords: conservation gaps, livelihood guilds, MaxEnt, protected area

Procedia PDF Downloads 388

Authors: M. M. Hassani, S. Ammann, F. K. Wittel, P. Niemz, H. J. Herrmann

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Application of engineered wood, especially in the form of glued-laminated timbers has increased significantly. Recent progress in plywood made of high strength and high stiffness hardwoods, like European beech, gives designers in general more freedom by increased dimensional stability and load-bearing capacity. However, the strong hygric dependence of basically all mechanical properties renders many innovative ideas futile. The tendency of hardwood for higher moisture sorption and swelling coefficients lead to significant residual stresses in glued-laminated configurations, cross-laminated patterns in particular. These stress fields cause initiation and evolution of cracks in the bond-lines resulting in: interfacial de-bonding, loss of structural integrity, and reduction of load-carrying capacity. Subsequently, delamination of glued-laminated timbers made of hardwood elements can be considered as the dominant failure mechanism in such composite elements. In addition, long-term creep and mechano-sorption under changing environmental conditions lead to loss of stiffness and can amplify delamination growth over the lifetime of a structure even after decades. In this study we investigate the delamination process of adhesively bonded hardwood (European beech) elements subjected to changing climatic conditions. To gain further insight into the long-term performance of adhesively bonded elements during the design phase of new products, the development and verification of an authentic moisture-dependent constitutive model for various species is of great significance. Since up to now, a comprehensive moisture-dependent rheological model comprising all possibly emerging deformation mechanisms was missing, a 3D orthotropic elasto-plastic, visco-elastic, mechano-sorptive material model for wood, with all material constants being defined as a function of moisture content, was developed. Apart from the solid wood adherends, adhesive layer also plays a crucial role in the generation and distribution of the interfacial stresses. Adhesive substance can be treated as a continuum layer constructed from finite elements, represented as a homogeneous and isotropic material. To obtain a realistic assessment on the mechanical performance of the adhesive layer and a detailed look at the interfacial stress distributions, a generic constitutive model including all potentially activated deformation modes, namely elastic, plastic, and visco-elastic creep was developed. We focused our studies on the three most common adhesive systems for structural timber engineering: one-component polyurethane adhesive (PUR), melamine-urea-formaldehyde (MUF), and phenol-resorcinol-formaldehyde (PRF). The corresponding numerical integration approaches, with additive decomposition of the total strain are implemented within the ABAQUS FEM environment by means of user subroutine UMAT. To predict the true stress state, we perform a history dependent sequential moisture-stress analysis using the developed material models for both wood substrate and adhesive layer. Prediction of the delamination process is founded on the fracture mechanical properties of the adhesive bond-line, measured under different levels of moisture content and application of the cohesive interface elements. Finally, we compare the numerical predictions with the experimental observations of de-bonding in glued-laminated samples under changing environmental conditions.

Keywords: engineered wood, adhesive, material model, FEM analysis, fracture mechanics, delamination

Procedia PDF Downloads 411

Authors: Gulce Kanturer Yasar, Hayriye Esbah Tuncay

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Cultivated food production systems have coexisted harmoniously with nature for thousands of years through ancient techniques. Based on this experience, experimentation, and discovery, these culturally embedded methods have evolved to sustain food production, restore ecosystems, and harmoniously adapt to nature. In this era, as we seek solutions to food security challenges, enhancing and repairing our food production systems is crucial, making them more resilient to future disasters without harming the ecosystem. Instead of unsustainable conventional systems with ongoing destructive effects, we must investigate innovative and restorative production systems that integrate ancient wisdom and technology. Whether we consider agricultural fields, pastures, forests, coastal wetland ecosystems, or lagoons, it is crucial to harness the potential of these natural resources in addressing future global challenges, fostering both socio-economic resilience and ecological sustainability through strategic organization for food production. When thoughtfully designed and managed, marine-based food production has the potential to function as a living infrastructure system that addresses social and environmental challenges despite its known adverse impacts on the environment and local economies. These areas are also stages of daily life, vibrant hubs where local culture is produced and shared, contributing to the distinctive rural character of coastal settlements and exhibiting numerous spatial expressions of public nature. When we consider the history of humanity, indigenous communities have engaged in these sustainable production practices that provide goods for food, trade, culture, and the environment for many ages. Ecosystem restoration and socio-economic resilience can be achieved by combining production techniques based on ecological knowledge developed by indigenous societies with modern technologies. Coastal lagoons are highly productive coastal features that provide various natural services and societal values. They are especially vulnerable to severe physical, ecological, and social impacts of changing, challenging global conditions because of their placement within the coastal landscape. Coastal lagoons are crucial in sustaining fisheries productivity, providing storm protection, supporting tourism, and offering other natural services that hold significant value for society. Although there is considerable literature on the physical and ecological dimensions of lagoons, much less literature focuses on their economic and social values. This study will discuss the possibilities of coastal lagoons to achieve both ecologically sustainable and socio-economically resilient while maintaining their productivity by combining local techniques and modern technologies. The case study will present Turkey’s traditional aquaculture method, "Dalyans," predominantly operated by small-scale farmers in coastal lagoons. Due to human, ecological, and economic factors, dalyans are losing their landscape characteristics and efficiency. These 1000-year-old ancient techniques, rooted in centuries of traditional and agroecological knowledge, are under threat of tourism, urbanization, and unsustainable agricultural practices. Thus, Dalyans have diminished from 29 to approximately 4-5 active Dalyans. To deal with the adverse socio-economic and ecological consequences on Turkey's coastal areas, conserving Dalyans by protecting their indigenous practices while incorporating contemporary methods is essential. This study seeks to generate scenarios that envision the potential ways protection and development can manifest within case study areas.

Keywords: coastal foodscape, lagoon aquaculture, regenerative food systems, watershed food networks

Procedia PDF Downloads 45

Authors: Kyriaki Hatziagapiou, Eleni Kakouri, Konstantinos Bethanis, Alexandra Nikola, Eleni Koniari, Charalabos Kanakis, Elias Christoforides, George Lambrou, Petros Tarantilis

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Medulloblastoma is a highly invasive tumour, as it tends to disseminate throughout the central nervous system early in its course. Despite the high 5-year-survival rate, a significant number of patients demonstrate serious long- or short-term sequelae (e.g., myelosuppression, endocrine dysfunction, cardiotoxicity, neurological deficits and cognitive impairment) and higher mortality rates, unrelated to the initial malignancy itself but rather to the aggressive treatment. A strong rationale exists for the use of Crocus sativus L (saffron) and its bioactive constituents (crocin, crocetin, safranal) as pharmaceutical agents, as they exert significant health-promoting properties. Crocins are water soluble carotenoids. Unlike other carotenoids, crocins are highly water-soluble compounds, with relatively low toxicity as they are not stored in adipose and liver tissues. Crocins have attracted wide attention as promising anti-cancer agents, due to their antioxidant, anti-inflammatory, and immunomodulatory effects, interference with transduction pathways implicated in tumorigenesis, angiogenesis, and metastasis (disruption of mitotic spindle assembly, inhibition of DNA topoisomerases, cell-cycle arrest, apoptosis or cell differentiation) and sensitization of cancer cells to radiotherapy and chemotherapy. The current research aimed to study the potential cytotoxic effect of crocins on TE671 medulloblastoma cell line, which may be useful in the optimization of existing and development of new therapeutic strategies. Crocins were extracted from stigmas of saffron in ultrasonic bath, using petroleum-ether, diethylether and methanol 70%v/v as solvents and the final extract was lyophilized. Identification of crocins according to high-performance liquid chromatography (HPLC) analysis was determined comparing the UV-vis spectra and the retention time (tR) of the peaks with literature data. For the biological assays crocin was diluted to nuclease and protease free water. TE671 cells were incubated with a range of concentrations of crocins (16, 8, 4, 2, 1, 0.5 and 0.25 mg/ml) for 24, 48, 72 and 96 hours. Analysis of cell viability after incubation with crocins was performed with Alamar Blue viability assay. The active ingredient of Alamar Blue, resazurin, is a blue, nontoxic, cell permeable compound virtually nonfluorescent. Upon entering cells, resazurin is reduced to a pink and fluorescent molecule, resorufin. Viable cells continuously convert resazurin to resorufin, generating a quantitative measure of viability. The colour of resorufin was quantified by measuring the absorbance of the solution at 600 nm with a spectrophotometer. HPLC analysis indicated that the most abundant crocins in our extract were trans-crocin-4 and trans-crocin-3. Crocins exerted significant cytotoxicity in a dose and time-dependent manner (p < 0.005 for exposed cells to any concentration at 48, 72 and 96 hours versus cells not exposed); as their concentration and time of exposure increased, the reduction of resazurin to resofurin decreased, indicating reduction in cell viability. IC50 values for each time point were calculated ~3.738, 1.725, 0.878 and 0.7566 mg/ml at 24, 48, 72 and 96 hours, respectively. The results of our study could afford the basis of research regarding the use of natural carotenoids as anticancer agents and the shift to targeted therapy with higher efficacy and limited toxicity. Acknowledgements: The research was funded by Fellowships of Excellence for Postgraduate Studies IKY-Siemens Programme.

Keywords: crocetin, crocin, medulloblastoma, saffron

Procedia PDF Downloads 195

Authors: L. Ereku, R. E. Mackay, A. Naveenathayalan, K. Ajayi, W. Balachandran

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Over the past decade the increase of sexually transmitted infections (STIs) especially in the developing world due to high cost and lack of sufficient medical testing have given rise to the need for a rapid, low cost point of care medical diagnostic that is disposable and most significantly reproduces equivocal results achieved within centralised laboratories. This paper present the development of a disposable PDMS microfluidic cartridge incorporating blisters filled with reagents required for isothermal DNA amplification in clinical diagnostics and point-of-care testing. In view of circumventing the necessity for external complex microfluidic pumps, designing on-chip pressurised fluid reservoirs is embraced using finger actuation and blister storage. The fabrication of the blisters takes into consideration three proponents that include: material characteristics, fluid volume and structural design. Silicone rubber is the chosen material due to its good chemical stability, considerable tear resistance and moderate tension/compression strength. The case of fluid capacity and structural form go hand in hand as the reagent need for the experimental analysis determines the volume size of the blisters, whereas the structural form has to be designed to provide low compression stress when deformed for fluid expulsion. Furthermore, the top and bottom section of the blisters are embedded with miniature polar opposite magnets at a defined parallel distance. These magnets are needed to lock or restrain the blisters when fully compressed so as to prevent unneeded backflow as a result of elasticity. The integrated chip is bonded onto a large microscope glass slide (50mm x 75mm). Each part is manufactured using a 3D printed mould designed using Solidworks software. Die-casting is employed, using 3D printed moulds, to form the deformable blisters by forcing a proprietary liquid silicone rubber through the positive mould cavity. The set silicone rubber is removed from the cast and prefilled with liquid reagent and then sealed with a thin (0.3mm) burstable layer of recast silicone rubber. The main microfluidic cartridge is fabricated using classical soft lithographic techniques. The cartridge incorporates microchannel circuitry, mixing chamber, inlet port, outlet port, reaction chamber and waste chamber. Polydimethylsiloxane (PDMS, QSil 216) is mixed and degassed using a centrifuge (ratio 10:1) is then poured after the prefilled blisters are correctly positioned on the negative mould. Heat treatment of about 50C to 60C in the oven for about 3hours is needed to achieve curing. The latter chip production stage involves bonding the cured PDMS to the glass slide. A plasma coroner treater device BD20-AC (Electro-Technic Products Inc., US) is used to activate the PDMS and glass slide before they are both joined and adequately compressed together, then left in the oven over the night to ensure bonding. There are two blisters in total needed for experimentation; the first will be used as a wash buffer to remove any remaining cell debris and unbound DNA while the second will contain 100uL amplification reagents. This paper will present results of chemical cell lysis, extraction using a biopolymer paper membrane and isothermal amplification on a low-cost platform using the finger actuated blisters for reagent storage. The platform has been shown to detect 1x105 copies of Chlamydia trachomatis using Recombinase Polymerase Amplification (RPA).

Keywords: finger actuation, point of care, reagent storage, silicone blisters

Procedia PDF Downloads 353

Authors: Xu Fei (Philip) WU

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

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

Procedia PDF Downloads 257

Authors: Volker Wannack

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Regional, national, and international strategies focusing on hydrogen (H₂) and blockchain are driving significant advancements in hydrogen and blockchain technology worldwide. These strategies lay the foundation for the groundbreaking "Blockchain Based Hydrogen Market (BBH₂)" project. The primary goal of this project is to develop a functional Blockchain Minimum Viable Product (B-MVP) for the hydrogen market. The B-MVP will leverage blockchain as an enabling technology with a common database and platform, facilitating secure and automated transactions through smart contracts. This innovation will revolutionize logistics, trading, and transactions within the hydrogen market. The B-MVP has transformative potential across various sectors. It benefits renewable energy producers, surplus energy-based hydrogen producers, hydrogen transport and distribution grid operators, and hydrogen consumers. By implementing standardized, automated, and tamper-proof processes, the B-MVP enhances cost efficiency and enables transparent and traceable transactions. Its key objective is to establish the verifiable integrity of climate-friendly "green" hydrogen by tracing its supply chain from renewable energy producers to end users. This emphasis on transparency and accountability promotes economic, ecological, and social sustainability while fostering a secure and transparent market environment. A notable feature of the B-MVP is its cross-border operability, eliminating the need for country-specific data storage and expanding its global applicability. This flexibility not only broadens its reach but also creates opportunities for long-term job creation through the establishment of a dedicated blockchain operating company. By attracting skilled workers and supporting their training, the B-MVP strengthens the workforce in the growing hydrogen sector. Moreover, it drives the emergence of innovative business models that attract additional company establishments and startups and contributes to long-term job creation. For instance, data evaluation can be utilized to develop customized tariffs and provide demand-oriented network capacities to producers and network operators, benefitting redistributors and end customers with tamper-proof pricing options. The B-MVP not only brings technological and economic advancements but also enhances the visibility of national and international standard-setting efforts. Regions implementing the B-MVP become pioneers in climate-friendly, sustainable, and forward-thinking practices, generating interest beyond their geographic boundaries. Additionally, the B-MVP serves as a catalyst for research and development, facilitating knowledge transfer between universities and companies. This collaborative environment fosters scientific progress, aligns with strategic innovation management, and cultivates an innovation culture within the hydrogen market. Through the integration of blockchain and hydrogen technologies, the B-MVP promotes holistic innovation and contributes to a sustainable future in the hydrogen industry. The implementation process involves evaluating and mapping suitable blockchain technology and architecture, developing and implementing the blockchain, smart contracts, and depositing certificates of origin. It also includes creating interfaces to existing systems such as nomination, portfolio management, trading, and billing systems, testing the scalability of the B-MVP to other markets and user groups, developing data formats for process-relevant data exchange, and conducting field studies to validate the B-MVP. BBH₂ is part of the "Technology Offensive Hydrogen" funding call within the research funding of the Federal Ministry of Economics and Climate Protection in the 7th Energy Research Programme of the Federal Government.

Keywords: hydrogen, blockchain, sustainability, innovation, structural change

Procedia PDF Downloads 146

Authors: Rowan Moore, Kai Scheffler, Eugen Damoc, Jennifer Sutton, Aaron Bailey, Stephane Houel, Simon Cubbon, Jonathan Josephs

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Purpose: MS analysis of monoclonal antibodies (mAbs) at the protein and peptide levels is critical during development and production of biopharmaceuticals. The compositions of current generation therapeutic proteins are often complex due to various modifications which may affect efficacy. Intact proteins analyzed by MS are detected in higher charge states that also provide more complexity in mass spectra. Protein analysis in native or native-like conditions with zero or minimal organic solvent and neutral or weakly acidic pH decreases charge state value resulting in mAb detection at higher m/z ranges with more spatial resolution. Methods: Three commercially available mAbs were used for all experiments. Intact proteins were desalted online using size exclusion chromatography (SEC) or reversed phase chromatography coupled on-line with a mass spectrometer. For streamlined use of the LC- MS platform we used a single SEC column and alternately selected specific mobile phases to perform separations in either denaturing or native-like conditions: buffer A (20 % ACN, 0.1 % FA) with Buffer B (100 mM ammonium acetate). For peptide analysis mAbs were proteolytically digested with and without prior reduction and alkylation. The mass spectrometer used for all experiments was a commercially available Thermo Scientific™ hybrid Quadrupole-Orbitrap™ mass spectrometer, equipped with the new BioPharma option which includes a new High Mass Range (HMR) mode that allows for improved high mass transmission and mass detection up to 8000 m/z. Results: We have analyzed the profiles of three mAbs under reducing and native conditions by direct infusion with offline desalting and with on-line desalting via size exclusion and reversed phase type columns. The presence of high salt under denaturing conditions was found to influence the observed charge state envelope and impact mass accuracy after spectral deconvolution. The significantly lower charge states observed under native conditions improves the spatial resolution of protein signals and has significant benefits for the analysis of antibody mixtures, e.g. lysine variants, degradants or sequence variants. This type of analysis requires the detection of masses beyond the standard mass range ranging up to 6000 m/z requiring the extended capabilities available in the new HMR mode. We have compared each antibody sample that was analyzed individually with mixtures in various relative concentrations. For this type of analysis, we observed that apparent native structures persist and ESI is benefited by the addition of low amounts of acetonitrile and formic acid in combination with the ammonium acetate-buffered mobile phase. For analyses on the peptide level we analyzed reduced/alkylated, and non-reduced proteolytic digests of the individual antibodies separated via reversed phase chromatography aiming to retrieve as much information as possible regarding sequence coverage, disulfide bridges, post-translational modifications such as various glycans, sequence variants, and their relative quantification. All data acquired were submitted to a single software package for analysis aiming to obtain a complete picture of the molecules analyzed. Here we demonstrate the capabilities of the mass spectrometer to fully characterize homogeneous and heterogeneous therapeutic proteins on one single platform. Conclusion: Full characterization of heterogeneous intact protein mixtures by improved mass separation on a quadrupole-Orbitrap™ mass spectrometer with extended capabilities has been demonstrated.

Keywords: disulfide bond analysis, intact analysis, native analysis, mass spectrometry, monoclonal antibodies, peptide mapping, post-translational modifications, sequence variants, size exclusion chromatography, therapeutic protein analysis, UHPLC

Procedia PDF Downloads 348

Authors: H. M. El-Askary, S. A. Abd El-Mawla, M. Allali, M. M. El-Hattab, M. El-Raey, A. M. Farahat, M. Kafatos, S. Nickovic, S. K. Park, A. K. Prasad, C. Rakovski, W. Sprigg, D. Struppa, A. Vukovic

Abstract:

A clear distinction between weather and climate is a necessity because while they are closely related, there are still important differences. Climate change is identified when we compute the statistics of the observed changes in weather over space and time. In this work we will show how the changing climate contribute to the frequency, magnitude and extent of different extreme events using a multi sensor approach with some synergistic modeling activities. We are exploring satellite observations of dust over North Africa, Gulf Region and the Indo Gangetic basin as well as dust versus anthropogenic pollution events over the Delta region in Egypt and Seoul through remote sensing and utilize the behavior of the dust and haze on the aerosol optical properties. Dust impact on the retreat of the glaciers in the Himalayas is also presented. In this study we also focus on the identification and monitoring of a massive dust plume that blew off the western coast of Africa towards the Atlantic on October 8th, 2012 right before the development of Hurricane Sandy. There is evidence that dust aerosols played a non-trivial role in the cyclogenesis process of Sandy. Moreover, a special dust event "An American Haboob" in Arizona is discussed as it was predicted hours in advance because of the great improvement we have in numerical, land–atmosphere modeling, computing power and remote sensing of dust events. Therefore we performed a full numerical simulation to that event using the coupled atmospheric-dust model NMME–DREAM after generating a mask of the potentially dust productive regions using land cover and vegetation data obtained from satellites. Climate change also contributes to the deterioration of different marine habitats. In that regard we are also presenting some work dealing with change detection analysis of Marine Habitats over the city of Hurghada, Red Sea, Egypt. The motivation for this work came from the fact that coral reefs at Hurghada have undergone significant decline. They are damaged, displaced, polluted, stepped on, and blasted off, in addition to the effects of climate change on the reefs. One of the most pressing issues affecting reef health is mass coral bleaching that result from an interaction between human activities and climatic changes. Over another location, namely California, we have observed that it exhibits highly-variable amounts of precipitation across many timescales, from the hourly to the climate timescale. Frequently, heavy precipitation occurs, causing damage to property and life (floods, landslides, etc.). These extreme events, variability, and the lack of good, medium to long-range predictability of precipitation are already a challenge to those who manage wetlands, coastal infrastructure, agriculture and fresh water supply. Adding on to the current challenges for long-range planning is climate change issue. It is known that La Niña and El Niño affect precipitation patterns, which in turn are entwined with global climate patterns. We have studied ENSO impact on precipitation variability over different climate divisions in California. On the other hand the Nile Delta has experienced lately an increase in the underground water table as well as water logging, bogging and soil salinization. Those impacts would pose a major threat to the Delta region inheritance and existing communities. There has been an undergoing effort to address those vulnerabilities by looking into many adaptation strategies.

Keywords: remote sensing, modeling, long range transport, dust storms, North Africa, Gulf Region, India, California, climate extremes, sea level rise, coral reefs

Procedia PDF Downloads 464

Authors: Elhadi Nasr, Ibrahim Ramadan

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Biostratigraphical analyses of well sections from the Maragh Low in the Eastern Sirt Basin has allowed high resolution correlations to be undertaken. Full integration of this data with available palaeoenvironmental, lithological, gravity, seismic, aeromagnetic, igneous, radiometric and wireline log information and a geochemical analysis of source rock quality and distribution has led to a more detailed understanding of the geological and the structural history of this area. Pre Sirt Unconformity two superimposed rifting cycles have been identified. The oldest is represented by the Amal Group of sediments and is of Late Carboniferous, Kasimovian / Gzelian to Middle Triassic, Anisian age. Unconformably overlying is a younger rift cycle which is represented the Sarir Group of sediments and is of Early Cretaceous, late Neocomian to Aptian in age. Overlying the Sirt Unconformity is the marine Late Cretaceous section. An assessment of pyrolysis results and a palynofacies analysis has allowed hydrocarbon source facies and quality to be determined. There are a number of hydrocarbon source rock horizons in the Maragh Low, these are sometimes vertically stacked and they are of fair to excellent quality. The oldest identified source rock is the Triassic Shale, this unit is unconformably overlain by sandstones belonging to the Sarir Group and conformably overlies a Triassic Siltstone unit. Palynological dating of the Triassic Shale unit indicates a Middle Triassic, Anisian age. The Triassic Shale is interpreted to have been deposited in a lacustrine palaeoenvironment. This particularly is evidenced by the dark, fine grained, organic rich nature of the sediment and is supported by palynofacies analysis and by the recovery of fish fossils. Geochemical analysis of the Triassic Shale indicates total organic carbon varying between 1.37 and 3.53. S2 pyrolysate yields vary between 2.15 mg/g and 6.61 mg/g and hydrogen indices vary between 156.91 and 278.91. The source quality of the Triassic Shale varies from being of fair to very good / rich. Linked to thermal maturity it is now a very good source for light oil and gas. It was once a very good to rich oil source. The Early Barremian Shale was also deposited in a lacustrine palaeoenvironment. Recovered palynomorphs indicate an Early Cretaceous, late Neocomian to early Barremian age. The Early Barremian Shale is conformably underlain and overlain by sandstone units belonging to the Sarir Group of sediments which are also of Early Cretaceous age. Geochemical analysis of the Early Barremian Shale indicates that it is a good oil source and was originally very good. Total organic carbon varies between 3.59% and 7%. S2 varies between 6.30 mg/g and 10.39 mg/g and the hydrogen indices vary between 148.4 and 175.5. A Late Barremian Shale unit of this age has also been identified in the central Maragh Low. Geochemical analyses indicate that total organic carbon varies between 1.05 and 2.38%, S2 pyrolysate between 1.6 and 5.34 mg/g and the hydrogen index between 152.4 and 224.4. It is a good oil source rock which is now mature. In addition to the non marine hydrocarbon source rocks pre Sirt Unconformity, three formations in the overlying Late Cretaceous section also provide hydrocarbon quality source rocks. Interbedded shales within the Rachmat Formation of Late Cretaceous, early Campanian age have total organic carbon ranging between, 0.7 and 1.47%, S2 pyrolysate varying between 1.37 and 4.00 mg/g and hydrogen indices varying between 195.7 and 272.1. The indication is that this unit would provide a fair gas source to a good oil source. Geochemical analyses of the overlying Tagrifet Limestone indicate that total organic carbon varies between 0.26% and 1.01%. S2 pyrolysate varies between 1.21 and 2.16 mg/g and hydrogen indices vary between 195.7 and 465.4. For the overlying Sirt Shale Formation of Late Cretaceous, late Campanian age, total organic carbon varies between 1.04% and 1.51%, S2 pyrolysate varies between 4.65 mg/g and 6.99 mg/g and the hydrogen indices vary between 151 and 462.9. The study has proven that both the Sirt Shale Formation and the Tagrifet Limestone are good to very good and rich sources for oil in the Maragh Low. High resolution biostratigraphical interpretations have been integrated and calibrated with thermal maturity determinations (Vitrinite Reflectance (%Ro), Spore Colour Index (SCI) and Tmax (ºC) and the determined present day geothermal gradient of 25ºC / Km for the Maragh Low. Interpretation of generated basin modelling profiles allows a detailed prediction of timing of maturation development of these source horizons and leads to a determination of amounts of missing section at major unconformities. From the results the top of the oil window (0.72% Ro) is picked as high as 10,700’ and the base of the oil window (1.35% Ro) assuming a linear trend and by projection is picked as low as 18,000’ in the Maragh Low. For the Triassic Shale the early phase of oil generation was in the Late Palaeocene / Early to Middle Eocene and the main phase of oil generation was in the Middle to Late Eocene. The Early Barremian Shale reached the main phase of oil generation in the Early Oligocene with late generation being reached in the Middle Miocene. For the Rakb Group section (Rachmat Formation, Tagrifet Limestone and Sirt Shale Formation) the early phase of oil generation started in the Late Eocene with the main phase of generation being between the Early Oligocene and the Early Miocene. From studying maturity profiles and from regional considerations it can be predicted that up to 500’ of sediment may have been deposited and eroded by the Sirt Unconformity in the central Maragh Low while up to 2000’ of sediment may have been deposited and then eroded to the south of the trough.

Keywords: Geochemical analysis of the source rocks from wells in Eastern Sirt Basin.

Procedia PDF Downloads 391

Authors: Charaia Vakhtang

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Global oil prices are seeing new bottoms every day. The prices have already collapsed beneath the psychological verge of 30 USD. This tendency would be fully acceptable for the Georgian consumers, but there is one detail: two our neighboring countries (one friendly and one hostile) largely depend on resources of these hydrocarbons. Namely, the ratio of Azerbaijan in Georgia’s total FDI inflows in 2014 marked 20%. The ratio reached 40% in the January to September 2015. Azerbaijan is Georgia’s leading exports market. Namely, in 2014 Georgia’s exports to Azerbaijan constituted 544 million USD, i.e. 19% in Georgia’s total experts. In the January to November period of 2015, the ratio exceeded 11%. Moreover, Azerbaijan is Georgia’s strategic partner country as part of many regional projects that are designated for long-term perspectives. For example, the Baku-Tbilisi-Karsi railroad, the Black Sea terminal, preferential gas tariffs for Georgia and so on. The Russian economic contribution to the Georgian economy is also considerable, despite the losses the Russian hostile policy has inflicted to our country. Namely, Georgian emigrants are mainly employed in the Russian Federation and this category of Georgian citizens transfers considerable funds to Georgia every year. These transfers account for about 1 billion USD and consequently, these funds previously equalized to total FDI inflows. Moreover, despite the difficulties in the Russian market, Russia still remains a leader in terms of money transfers to Georgia. According to the last reports, money transfers from Russia to Georgia slipped by 276 million USD in 2015 compared to 2014 (-39%). At the same time, the total money transfers to Georgia in 2015 marked 1.08 billion USD, down 25% from 1.44 billion USD in 2014. This signifies the contraction in money transfers is by ¾ dependent on the Russian factor (in this case, contraction in oil prices and the Russian Ruble devaluation directly make negative impact on money transfers to Georgia). As to other countries, it is interesting that money transfers have also slipped from Italy (to 109 million USD from 121 million USD). Nevertheless, the country’s ratio in total money transfers to Georgia has increased to 10% from 8%. Money transfers to Georgia have increased by 22% (+18 million USD) from the USA. Money transfers have halved from Greece to 117 million USD from 205 million USD. As to Turkey, money transfers to Georgia from Turkey have increased by 1% to 69 million USD. Moreover, the problems with the national currencies of Russia and Azerbaijan, along with the above-mentioned developments, outline unfavorable perspectives for the Georgian economy. The depreciation of the national currencies of Azerbaijan and Russia is expected to bring unfavorable results for the Georgian economy. Even more so, the statement released by the Russian Finance Ministry on expected default is in direct relation to the welfare of the whole region and these tendencies will make direct and indirect negative impacts on Georgia’s economic indicators. Amid the economic slowdown in Armenia, Turkey and Ukraine, Georgia should try to enhance economic ties with comparatively stronger and flexible economies such as EU and USA. In other case, the Georgian economy will enter serious turbulent zone. We should make maximum benefit from the EU association agreement. It should be noted that the Russian economy slowdown that causes both regretful and happy moods in Georgia, will make negative impact on the Georgian economy. The same forecasts are made in relation to Azerbaijan. However, Georgia has many partner countries. Enhancement and development of the economic relations with these countries may maximally alleviate negative impacts from the declining economies. First of all, the EU association agreement should be mentioned as a main source for Georgia’s economic stabilization. It is the Georgian government‘s responsibility to successfully fulfill the EU association agreement requirements. In any case the imports must be replaced by domestic products and the exports should be stimulated through government support programs. The Authorities should ensure drawing more foreign investments and money resources, accumulating more tourism revenues and reducing external debts, budget expenditures should be balanced and the National Bank should carry out strict monetary policy. Moreover, the Government should develop a long-term state economic policy and carry out this policy at various Ministries. It is also of crucial importance to carry out constitutive policy and promote perspective directions on the domestic level.

Keywords: oil prices, economic growth, foreign direct investments, international trade

Procedia PDF Downloads 252

Authors: Istvan Csarnovics, Attila Bonyar, Miklos Veres, Laszlo Himics, Attila Csik, Judit Kaman, Julia Burunkova, Geza Szanto, Laszlo Balazs, Sandor Kokenyesi

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In this work, the performance of gold nanoparticles were investigated for stimulation of photosensitive materials for photonic applications. It was widely used for surface plasmon resonance experiments, not in the last place because of the manifestation of optical resonances in the visible spectral region. The localized surface plasmon resonance is rather easily observed in nanometer-sized metallic structures and widely used for measurements, sensing, in semiconductor devices and even in optical data storage. Firstly, gold nanoparticles on silica glass substrate satisfy the conditions for surface plasmon resonance in the green-red spectral range, where the chalcogenide glasses have the highest sensitivity. The gold nanostructures influence and enhance the optical, structural and volume changes and promote the exciton generation in gold nanoparticles/chalcogenide layer structure. The experimental results support the importance of localized electric fields in the photo-induced transformation of chalcogenide glasses as well as suggest new approaches to improve the performance of these optical recording media. Results may be utilized for direct, micrometre- or submicron size geometrical and optical pattern formation and used also for further development of the explanations of these effects in chalcogenide glasses. Besides of that, gold nanoparticles could be added to the organic light-sensitive material. The acrylate-based materials are frequently used for optical, holographic recording of optoelectronic elements due to photo-stimulated structural transformations. The holographic recording process and photo-polymerization effect could be enhanced by the localized plasmon field of the created gold nanostructures. Finally, gold nanoparticles widely used for electrochemical and optical sensor applications. Although these NPs can be synthesized in several ways, perhaps one of the simplest methods is the thermal annealing of pre-deposited thin films on glass or silicon surfaces. With this method, the parameters of the annealing process (time, temperature) and the pre-deposited thin film thickness influence and define the resulting size and distribution of the NPs on the surface. Localized surface plasmon resonance (LSPR) is a very sensitive optical phenomenon and can be utilized for a large variety of sensing purposes (chemical sensors, gas sensors, biosensors, etc.). Surface-enhanced Raman spectroscopy (SERS) is an analytical method which can significantly increase the yield of Raman scattering of target molecules adsorbed on the surface of metallic nanoparticles. The sensitivity of LSPR and SERS based devices is strongly depending on the used material and also on the size and geometry of the metallic nanoparticles. By controlling these parameters the plasmon absorption band can be tuned and the sensitivity can be optimized. The technological parameters of the generated gold nanoparticles were investigated and influence on the SERS and on the LSPR sensitivity was established. The LSPR sensitivity were simulated for gold nanocubes and nanospheres with MNPBEM Matlab toolbox. It was found that the enhancement factor (which characterize the increase in the peak shift for multi-particle arrangements compared to single-particle models) depends on the size of the nanoparticles and on the distance between the particles. This work was supported by GINOP- 2.3.2-15-2016-00041 project, which is co-financed by the European Union and European Social Fund. Istvan Csarnovics is grateful for the support through the New National Excellence Program of the Ministry of Human Capacities, supported by the ÚNKP-17-4 Attila Bonyár and Miklós Veres are grateful for the support of the János Bolyai Research Scholarship of the Hungarian Academy of Sciences.

Keywords: light sensitive nanocomposites, metallic nanoparticles, photonic application, plasmonic nanostructures

Procedia PDF Downloads 280

Authors: Stephen Verderber

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The World Health Organization (WHO) calls for research and development on ecologically sustainable, resilient structures capable of effectively responding to disaster events globally, in response to climate change, politically based diasporas, earthquakes, and other adverse events upending the rhythms of everyday life globally. By 2050, nearly 80% of the world’s population will reside in coastal zones, and this, coupled with the increasingly dire impacts of climate change, constitute a recipe for further chaos and disruption, and in light of these events, architects have yet to rise up to meet the challenge. In the arena of healthcare, rapidly deployable clinics and field hospitals can provide immediate assistance in medically underserved disaster strike zones. Transportable facilities offer multiple advantages over conventional, fixed-site hospitals, as lightweight, comparatively unencumbered alternatives. These attributes have been proven repeatedly in 20th century vehicular and tent-based structures deployed in frontline combat theaters and in prior natural disasters. Prefab transportable clinics and trauma centers recently responded adroitly to medical emergencies in the aftermath of the Haitian (2010) and Ecuadorian (2016) earthquakes, and in North American post-hurricane relief efforts (2017) while architects continue to be castigated by their engineer colleagues as chronically poor first responders. Architecturally based portable structures for healthcare currently include Redeployable Health Centers (RHCs), Redeployable Trauma Centers (RTCs), and Permanent Modular Installations (PMIs). Five tectonic variants within this typology have recently been operationalized in the field: 1. Vehicular-based Nomadics: Prefab modules installed on a truck chassis with interior compartments dropped in prior to final assembly. Alternately, a two-component apparatus is preferred, with a truck cab pulling a modular medical unit, with independent transiting component; 2. Tent and Pneumatic Systems: Tent/yurt precursors and inflatable systems lightweight and responsive to topographically challenging terrain and diverse climates; 3. Containerized Systems: The standard modular intermodal-shipping container affords structural strength, resiliency in difficult transiting conditions, and can be densely close-packed and these can be custom-built or hold flat-pack systems; 4. Flat-Packs and Pop-Up Systems: These kit-of-part assemblies are shipped in standardized or specially-designed ISO containers; and 5. Hybrid Systems: These consist of composite facilities representing a synthesis of mobile vehicular components and/or tent or shipping containers, fused with conventional or pneumatically activated tent systems. Hybrids are advantageous in many installation contexts from an aesthetic, fabrication, and transiting perspective. Advantages/disadvantages of various modular systems are comparatively examined, followed by presentation of a compendium of 80 evidence (research)-based planning and design considerations addressing site/context, transiting and commissioning, triage, decontamination/intake, diagnostic and treatment, facility tectonics, and administration/total environment. The benefits of offsite pre-manufactured fabrication are examined, as is anticipated growth in international demand for transportable healthcare facilities to meet the challenges posed by accelerating global climate change and global conflicts. This investigation into rapid response facilities for pre and post-disaster zones is drawn from a recent book by the author, the first on architecture on this topic (Innovations in Transportable Healthcare Architecture).

Keywords: disaster mitigation, rapid response healthcare architecture, offsite prefabrication

Procedia PDF Downloads 102

Authors: Maria João Ferreira, Natalia Sierra-Garcia, Javier Cremades, Carla António, Ana M. Rodrigues, Helena Silva, Ângela Cunha

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Salicornia ramosissima, a halophyte that grows naturally in coastal areas of the northern hemisphere, is often considered the most promising halophyte candidate for extensive crop cultivation and saline agriculture practices. The expanding interest in this plant surpasses its use as gourmet food and includes their potential application as a source of bioactive compounds for the pharmaceutical industry. Despite growing well in saline soils, sustainable and ecologically friendly techniques to enhance crop production and the nutritional value of this plant are still needed. The root microbiome of S. ramosissima proved to be a source of taxonomically diverse plant growth-promoting bacteria (PGPB). Halotolerant strains of Bacillus, Salinicola, Pseudomonas, and Brevibacterium, among other genera, exhibit a broad spectrum of plant-growth promotion traits [e.g., 3-indole acetic acid (IAA), 1-aminocyclopropane-1-carboxylic acid (ACC) deaminase, siderophores, phosphate solubilization, Nitrogen fixation] and express a wide range of extracellular enzyme activities. In this work, three plant growth-promoting bacteria strains (Brevibacterium casei EB3, Pseudomonas oryzihabitans RL18, and Bacillus aryabhattai SP20) isolated from the rhizosphere and the endosphere of S. ramosissima roots from different saltmarshes along the Portuguese coast were inoculated in S. ramosissima seeds. Plants germinated from inoculated seeds were grown for three months in pots filled with a mixture of perlite and estuarine sediment (1:1) in greenhouse conditions and later transferred to a growth chamber, where they were maintained two months with controlled photoperiod, temperature, and humidity. Pots were placed on trays containing the irrigation solution (Hoagland’s solution 20% added with 10‰ marine salt). Before reaching the flowering stage, plants were collected, and the fresh and dry weight of aerial parts was determined. Non-inoculated seeds were used as a negative control. Selected dried stems from the most promising treatments were later analyzed by GC-TOF-MS for primary metabolite composition. The efficiency of inoculation and persistence of the inoculum was assessed by Next Generation Sequencing. Inoculations with single strain EB3 and co-inoculations with EB3+RL18 and EB3+RL18+SP20 (All treatment) resulted in significantly higher biomass production (fresh and dry weight) compared to non-inoculated plants. Considering fresh weight alone, inoculation with isolates SP20 and RL18 also caused a significant positive effect. Combined inoculation with the consortia SP20+EB3 or SP20+RL18 did not significantly improve biomass production. The analysis of the profile of primary metabolites will provide clues on the mechanisms by which the growth-enhancement effect of the inoculants operates in the plants. These results sustain promising prospects for the use of rhizospheric and endophytic PGPB as biofertilizers, reducing environmental impacts and operational costs of agrochemicals and contributing to the sustainability and cost-effectiveness of saline agriculture. Acknowledgments: This work was supported by project Rhizomis PTDC/BIA-MIC/29736/2017 financed by Fundação para a Ciência e Tecnologia (FCT) through the Regional Operational Program of the Center (02/SAICT/2017) with FEDER funds (European Regional Development Fund, FNR, and OE) and by FCT through CESAM (UIDP/50017/2020 + UIDB/50017/2020), LAQV-REQUIMTE (UIDB/50006/2020). We also acknowledge FCT/FSE for the financial support to Maria João Ferreira through a PhD grant (PD/BD/150363/2019). We are grateful to Horta dos Peixinhos for their help and support during sampling and seed collection. We also thank Glória Pinto for her collaboration providing us the use of the growth chambers during the final months of the experiment and Enrique Mateos-Naranjo and Jennifer Mesa-Marín of the Departamento de Biología Vegetal y Ecología, the University of Sevilla for their advice regarding the growth of salicornia plants in greenhouse conditions.

Keywords: halophytes, PGPB, rhizosphere engineering, biofertilizers, primary metabolite profiling, plant inoculation, Salicornia ramosissima

Procedia PDF Downloads 139

Authors: Hosein Maghsoudi

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

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

Procedia PDF Downloads 367

Authors: Guilherme Giacomini, Ana Luiza Menegatti Pavan, Allan Felipe Fattori Alves, Marcela de Oliveira, Fernando Antonio Bacchim Neto, José Ricardo de Arruda Miranda, Seizo Yamashita, Diana Rodrigues de Pina

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The maxillary sinus (MS), part of the paranasal sinus complex, is one of the most enigmatic structures in modern humans. The literature has suggested that MSs function as olfaction accessories, to heat or humidify inspired air, for thermoregulation, to impart resonance to the voice and others. Thus, the real function of the MS is still uncertain. Furthermore, the MS anatomy is complex and varies from person to person. Many diseases may affect the development process of sinuses. The incidence of rhinosinusitis and other pathoses in the MS is comparatively high, so, volume analysis has clinical value. Providing volume values for MS could be helpful in evaluating the presence of any abnormality and could be used for treatment planning and evaluation of the outcome. The computed tomography (CT) has allowed a more exact assessment of this structure, which enables a quantitative analysis. However, this is not always possible in the clinical routine, and if possible, it involves much effort and/or time. Therefore, it is necessary to have a convenient, robust, and practical tool correlated with the MS volume, allowing clinical applicability. Nowadays, the available methods for MS segmentation are manual or semi-automatic. Additionally, manual methods present inter and intraindividual variability. Thus, the aim of this study was to develop an automatic tool to quantity the MS volume in CT scans of paranasal sinuses. This study was developed with ethical approval from the authors’ institutions and national review panels. The research involved 30 retrospective exams of University Hospital, Botucatu Medical School, São Paulo State University, Brazil. The tool for automatic MS quantification, developed in Matlab®, uses a hybrid method, combining different image processing techniques. For MS detection, the algorithm uses a Support Vector Machine (SVM), by features such as pixel value, spatial distribution, shape and others. The detected pixels are used as seed point for a region growing (RG) segmentation. Then, morphological operators are applied to reduce false-positive pixels, improving the segmentation accuracy. These steps are applied in all slices of CT exam, obtaining the MS volume. To evaluate the accuracy of the developed tool, the automatic method was compared with manual segmentation realized by an experienced radiologist. For comparison, we used Bland-Altman statistics, linear regression, and Jaccard similarity coefficient. From the statistical analyses for the comparison between both methods, the linear regression showed a strong association and low dispersion between variables. The Bland–Altman analyses showed no significant differences between the analyzed methods. The Jaccard similarity coefficient was > 0.90 in all exams. In conclusion, the developed tool to quantify MS volume proved to be robust, fast, and efficient, when compared with manual segmentation. Furthermore, it avoids the intra and inter-observer variations caused by manual and semi-automatic methods. As future work, the tool will be applied in clinical practice. Thus, it may be useful in the diagnosis and treatment determination of MS diseases. Providing volume values for MS could be helpful in evaluating the presence of any abnormality and could be used for treatment planning and evaluation of the outcome. The computed tomography (CT) has allowed a more exact assessment of this structure which enables a quantitative analysis. However, this is not always possible in the clinical routine, and if possible, it involves much effort and/or time. Therefore, it is necessary to have a convenient, robust and practical tool correlated with the MS volume, allowing clinical applicability. Nowadays, the available methods for MS segmentation are manual or semi-automatic. Additionally, manual methods present inter and intraindividual variability. Thus, the aim of this study was to develop an automatic tool to quantity the MS volume in CT scans of paranasal sinuses. This study was developed with ethical approval from the authors’ institutions and national review panels. The research involved 30 retrospective exams of University Hospital, Botucatu Medical School, São Paulo State University, Brazil. The tool for automatic MS quantification, developed in Matlab®, uses a hybrid method, combining different image processing techniques. For MS detection, the algorithm uses a Support Vector Machine (SVM), by features such as pixel value, spatial distribution, shape and others. The detected pixels are used as seed point for a region growing (RG) segmentation. Then, morphological operators are applied to reduce false-positive pixels, improving the segmentation accuracy. These steps are applied in all slices of CT exam, obtaining the MS volume. To evaluate the accuracy of the developed tool, the automatic method was compared with manual segmentation realized by an experienced radiologist. For comparison, we used Bland-Altman statistics, linear regression and Jaccard similarity coefficient. From the statistical analyses for the comparison between both methods, the linear regression showed a strong association and low dispersion between variables. The Bland–Altman analyses showed no significant differences between the analyzed methods. The Jaccard similarity coefficient was > 0.90 in all exams. In conclusion, the developed tool to automatically quantify MS volume proved to be robust, fast and efficient, when compared with manual segmentation. Furthermore, it avoids the intra and inter-observer variations caused by manual and semi-automatic methods. As future work, the tool will be applied in clinical practice. Thus, it may be useful in the diagnosis and treatment determination of MS diseases.

Keywords: maxillary sinus, support vector machine, region growing, volume quantification

Procedia PDF Downloads 491

Authors: Ziyad S. Haidar

Abstract:

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

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

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