Search results for: comparative modeling

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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Authors: Mehmet Salih Bayraktutan

Abstract:

Geomechanical properties of Rock Salt Deposits in Tuzluca Salt Mine Area (Eastern Turkey) are studied for modeling the operation- excavation strategy. The purpose of this research focused on calculating the critical value of span height- which will meet the safety requirements. The Mine Site Tuzluca Hills consist of alternating parallel bedding of Salt ( NaCl ) and Gypsum ( CaS04 + 2 H20) rocks. Rock Salt beds are more resistant than narrow Gypsum interlayers. Rock Salt beds formed almost 97 percent of the total height of the Hill. Therefore, the geotechnical safety of Galleries depends on the mechanical criteria of Rock Salt Cores. General deposition of Tuzluca Basin was finally completed by Tuzluca Evaporites, as for the uppermost stratigraphic unit. They are currently running mining operations performed by classic mechanical excavation, room and pillar method. Rooms and Pillars are currently experiencing an initial stage of fracturing in places. Geotechnical safety of the whole mining area evaluated by Rock Mass Rating (RMR), Rock Quality Designation (RQD) spacing of joints, and the interaction of groundwater and fracture system. In general, bedded rock salt Show large lateral deformation capacity (while deformation modulus stays in relative small values, here E= 9.86 GPa). In such litho-stratigraphic environments, creep is a critical mechanism in failure. Rock Salt creep rate in steady-state is greater than interbedding layers. Under long-lasted compressive stresses, creep may cause shear displacements, partly using bedding planes. Eventually, steady-state creep in time returns to accelerated stages. Uniaxial compression creep tests on specimens were performed to have an idea of rock salt strength. To give an idea, on Rock Salt cores, average axial strength and strain are found as 18 - 24 MPa and 0.43-0.45 %, respectively. Uniaxial Compressive strength of 26- 32 MPa, from bedded rock salt cores. Elastic modulus is comparatively low, but lateral deformation of the rock salt is high under the uniaxial compression stress state. Poisson ratio = 0.44, break load = 156 kN, cohesion c= 12.8 kg/cm2, specific gravity SG=2.17 gr/cm3. Fracture System; spacing of fractures, joints, faults, offsets are evaluated under acting geodynamic mechanism. Two sand beds, each 4-6 m thick, exist near to upper level and at the top of the evaporating sequence. They act as aquifers and keep infiltrated water on top for a long duration, which may result in the failure of roofs or pillars. Two major active seismic ( N30W and N70E ) striking Fault Planes and parallel fracture strands have seismically triggered moderate risk of structural deformation of rock salt bedding sequence. Earthquakes and Floods are two prevailing sources of geohazards in this region—the seismotectonic activity of the Mine Site based on the crossing framework of Kagizman Faults and Igdir Faults. Dominant Hazard Risk sources include; a) Weak mechanical properties of rock salt, gypsum, anhydrite beds-creep. b) Physical discontinuities cutting across the thick parallel layers of Evaporite Mass, c) Intercalated beds of weak cemented or loose sand, clayey sandy sediments. On the other hand, absorbing the effects of salt-gyps parallel bedded deposits on seismic wave amplitudes has a reducing effect on the Rock Mass.

Keywords: bedded rock salt, creep, failure mechanism, geotechnical safety

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Authors: Carlotta D’Alessandro, Giuseppe Ioppolo, Katarzyna Szopik-Depczyńska

Abstract:

— The growing scarcity of resources and the mounting pressures of climate change, water pollution, and chemical contamination have prompted societies, governments, and businesses to seek ways to minimize their environmental impact. To combat climate change, and foster sustainability, Industrial Symbiosis (IS) offers a powerful approach, facilitating the shift toward a circular economic model. IS has gained prominence in the European Union's policy framework as crucial enabler of resource efficiency and circular economy practices. The essence of IS lies in the collaborative sharing of resources such as energy, material by-products, waste, and water, thanks to geographic proximity. It can be exemplified by eco-industrial parks (EIPs), which are natural environments for boosting cooperation and resource sharing between businesses. EIPs are characterized by group of businesses situated in proximity, connected by a network of both cooperative and competitive interactions. They represent a sustainable industrial model aimed at reducing resource use, waste, and environmental impact while fostering economic and social wellbeing. IS, combined with Artificial Intelligence (AI)-driven technologies, can further optimize resource sharing and efficiency within EIPs. This research, supported by the “CE_IPs” project, aims to analyze the potential for IS and AI, in advancing circularity and sustainability at Fosso Imperatore. The Fosso Imperatore Industrial Park in Nocera Inferiore, Italy, specializes in agriculture and the industrial transformation of agricultural products, particularly tomatoes, tobacco, and textile fibers. This unique industrial cluster, centered around tomato cultivation and processing, also includes mechanical engineering enterprises and agricultural packaging firms. To stimulate the shift from a traditional to a circular economic model, an AI-powered Local Development Plan (LDP) is developed for Fosso Imperatore. It can leverage data analytics, predictive modeling, and stakeholder engagement to optimize resource utilization, reduce waste, and promote sustainable industrial practices. A comprehensive SWOT analysis of the AI-powered LDP revealed several key factors influencing its potential success and challenges. Among the notable strengths and opportunities arising from AI implementation are reduced processing times, fewer human errors, and increased revenue generation. Furthermore, predictive analytics minimize downtime, bolster productivity, and elevate quality while mitigating workplace hazards. However, the integration of AI also presents potential weaknesses and threats, including significant financial investment, since implementing and maintaining AI systems can be costly. The widespread adoption of AI could lead to job losses in certain sectors. Lastly, AI systems are susceptible to cyberattacks, posing risks to data security and operational continuity. Moreover, an Analytic Hierarchy Process (AHP) analysis was employed to yield a prioritized ranking of the outlined AI-driven LDP practices based on the stakeholder input, ensuring a more comprehensive and representative understanding of their relative significance for achieving sustainability in Fosso Imperatore Industrial Park. While this study provides valuable insights into the potential of AIpowered LDP at the Fosso Imperatore, it is important to note that the findings may not be directly applicable to all industrial parks, particularly those with different sizes, geographic locations, or industry compositions. Additional study is necessary to scrutinize the generalizability of these results and to identify best practices for implementing AI-driven LDP in diverse contexts.

Keywords: artificial intelligence, climate change, Fosso Imperatore, industrial park, industrial symbiosis

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