Search results for: chemical graph
Commenced in January 2007
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Paper Count: 4944

Search results for: chemical graph

24 Urban Ecosystem Health and Urban Agriculture

Authors: Mahbuba Kaneez Hasna

Abstract:

Introductory Statement outlining the background: Little has been written about political ecology of urban gardening, such as a network of knowledge generation, technologies of food production and distribution, food consumption practices, and the regulation of ‘agricultural activities. For urban food gardens to sustain as a long-term food security enterprise, we will need to better understand the anthropological, ecological, political, and institutional factors influencing their development, management, and ongoing viability. Significance of the study: Dhaka as one of the fastest growing city. There are currently no studies regards to Bangladesh on how urban slum dwellerscope with the changing urban environment in the city, where they overcome challenges, and how they cope with the urban ecological cycle of food and vegetable production. It is also essential to understand the importance of their access to confined spaces in the slums they apply their indigenous knowledge. These relationships in nature are important factors in community and conservation ecology. Until now, there has been no significant published academic work on relationships between urban and environmental anthropology, urban planning, geography, ecology, and social anthropology with a focus on urban agriculture and how this contributes to the moral economies, indigenous knowledge, and government policies in order to improve the lives and livelihoods of slum dwellers surrounding parks and open spaces in Dhaka, Bangladesh. Methodology: it have applied participant observation, semi-structured questionnaire-based interviews, and focus group discussions to collect social data. Interviews were conducted with the urban agriculture practitioners who are slum dwellers who carry out their urban agriculture activities. Some of the interviews were conducted with non-government organisations (NGOs) and local and state government officials, using semi-structured interviews. Using these methods developed a clearer understanding of how green space cultivation, local economic self-reliance, and urban gardening are producing distinctive urban ecologies in Dhaka and their policy-implications on urban sustainability. Major findings of the study: The research provided an in-depth knowledge on the challenges that slum dwellers encounter in establishing and maintaining urban gardens, such as the economic development of the city, conflicting political agendas, and environmental constraints in areas within which gardening activities take place. The research investigated (i) How do slum dwellers perform gardening practices from rural areas to open spaces in the city? (ii) How do men and women’s ethno-botanical knowledge contribute to urban biodiversity; (iii) And how do slum dwellers navigate complex constellations of land use policy, competing political agendas, and conflicting land and water tenures to meet livelihood functions provided by their gardens. Concluding statement: Lack of infrastructure facilities such as water supply and sanitation, micro-drains and waste disposal areas, and poor access to basic health care services increase the misery of people in the slum areas. Lack of environmental health awareness information for farmers, such as the risks from the use of chemical pesticides in gardens and from grazing animals in contaminated fields or cropping and planting trees or vegetable in contaminated dumping grounds, can all cause high health risk to humans and their environment.

Keywords: gender, urban agriculture, ecosystem health, urban slum systems

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23 Linking the Genetic Signature of Free-Living Soil Diazotrophs with Process Rates under Land Use Conversion in the Amazon Rainforest

Authors: Rachel Danielson, Brendan Bohannan, S.M. Tsai, Kyle Meyer, Jorge L.M. Rodrigues

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The Amazon Rainforest is a global diversity hotspot and crucial carbon sink, but approximately 20% of its total extent has been deforested- primarily for the establishment of cattle pasture. Understanding the impact of this large-scale disturbance on soil microbial community composition and activity is crucial in understanding potentially consequential shifts in nutrient or greenhouse gas cycling, as well as adding to the body of knowledge concerning how these complex communities respond to human disturbance. In this study, surface soils (0-10cm) were collected from three forests and three 45-year-old pastures in Rondonia, Brazil (the Amazon state with the greatest rate of forest destruction) in order to determine the impact of forest conversion on microbial communities involved in nitrogen fixation. Soil chemical and physical parameters were paired with measurements of microbial activity and genetic profiles to determine how community composition and process rates relate to environmental conditions. Measuring both the natural abundance of 15N in total soil N, as well as incorporation of enriched 15N2 under incubation has revealed that conversion of primary forest to cattle pasture results in a significant increase in the rate of nitrogen fixation by free-living diazotrophs. Quantification of nifH gene copy numbers (an essential subunit encoding the nitrogenase enzyme) correspondingly reveals a significant increase of genes in pasture compared to forest soils. Additionally, genetic sequencing of both nifH genes and transcripts shows a significant increase in the diversity of the present and metabolically active diazotrophs within the soil community. Levels of both organic and inorganic nitrogen tend to be lower in pastures compared to forests, with ammonium rather than nitrate as the dominant inorganic form. However, no significant or consistent differences in total, extractable, permanganate-oxidizable, or loss-on-ignition carbon are present between the two land-use types. Forest conversion is associated with a 0.5- 1.0 unit pH increase, but concentrations of many biologically relevant nutrients such as phosphorus do not increase consistently. Increases in free-living diazotrophic community abundance and activity appear to be related to shifts in carbon to nitrogen pool ratios. Furthermore, there may be an important impact of transient, low molecular weight plant-root-derived organic carbon on free-living diazotroph communities not captured in this study. Preliminary analysis of nitrogenase gene variant composition using NovoSeq metagenomic sequencing indicates that conversion of forest to pasture may significantly enrich vanadium-based nitrogenases. This indication is complemented by a significant decrease in available soil molybdenum. Very little is known about the ecology of diazotrophs utilizing vanadium-based nitrogenases, so further analysis may reveal important environmental conditions favoring their abundance and diversity in soil systems. Taken together, the results of this study indicate a significant change in nitrogen cycling and diazotroph community composition with the conversion of the Amazon Rainforest. This may have important implications for the sustainability of cattle pastures once established since nitrogen is a crucial nutrient for forage grass productivity.

Keywords: free-living diazotrophs, land use change, metagenomic sequencing, nitrogen fixation

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22 Amniotic Fluid Mesenchymal Stem Cells Selected for Neural Specificity Ameliorates Chemotherapy Induced Hearing Loss and Pain Perception

Authors: Jan F. Talts, Amit Saxena, Kåre Engkilde

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Chemotherapy-induced peripheral neuropathy (CIPN) is one of the most frequent side effects caused by anti-neoplastic agents, with a prevalence from 19 % to 85 %. Clinically, CIPN is a mostly sensory neuropathy leading to pain and to motor and autonomic changes. Due to its high prevalence among cancer patients, CIPN constitutes a major problem for both cancer patients and survivors, especially because currently, there is no single effective method of preventing CIPN. Hearing loss is the most common form of sensory impairment in humans and can be caused by ototoxic chemical compounds such as chemotherapy (platinum-based antineoplastic agents).In rodents, single or repeated cisplatin injections induce peripheral neuropathy and hearing impairment mimicking human disorder, allowing studying the efficacy of new pharmacological candidates in chemotherapy-induced hearing loss and peripheral neuropathy. RNA sequencing data from full term amniotic fluid (TAF) mesenchymal stemcell (MSC) clones was used to identify neural-specific markers present on TAF-MSC. Several prospective neural markers were tested by flow cytometry on cultured TAF-MSC. One of these markers was used for cell-sorting using Tyto MACSQuant cell sorter, and the neural marker positive cell population was expanded for several passages to the final therapeutic product stage. Peripheral neuropathy and hearing loss was induced in mice by administration of cisplatin in three week-long cycles. The efficacy of neural-specific TAF-MSC in treating hearing loss and pain perception was evaluated by administration of three injections of 3 million cells/kg by intravenous route or three injections of 3 million cells/kg by intra-arterial route after each cisplatin cycle treatment. Auditory brainstem responses (ABR) are electric potentials recorded from scalp electrodes, and the first ABR wave represents the summed activity of the auditory nerve fibers contacting the inner hair cells. For ABR studies, mice were anesthetized, then earphones were placed in the left ear of each mouse, an active electrode was placed in the vertex of the skull, a reference electrode under the skin of the mastoid bone, and a ground electrode in the neck skin. The stimuli consisted of tone pips of five frequencies (2, 4, 6, 12, 16, and 24 kHz) at various sound levels (from 0 to 90 dB) ranging to cover the mouse auditory frequency range. The von Frey test was used to assess the onset and maintenance of mechanical allodynia over time. Mice were placed in clear plexiglass cages on an elevated mesh floor and tested after 30 min of habituation. Mechanical paw withdrawal threshold was examined using an electronic von Frey anesthesiometer. Cisplatin groups treated with three injections of 3 million cells/kg by intravenous route and three injections of 3 million cells/kg by intra-arterial route after each cisplatin cycle treatment presented, a significant increase of hearing acuity characterized by a decrease of ABR threshold and a decrease of neuropathic pain characterized by an increase of von Frey paw withdrawal threshold compared to controls only receiving cisplatin. This study shows that treatment with MSCselected for neural specificity presents significant positive efficacy on the chemotherapy-induced neuropathic pain and the chemotherapy-induced hearing loss.

Keywords: mesenchymal stem cell, peripheral neuropathy, amniotic fluid, regenerative medicine

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21 Successful Public-Private Partnership Through the Impact of Environmental Education: A Case Study on Transforming Community Confrict into Harmony in the Dongpian Community

Authors: Men An Pan, Ho Hsiung Huang, Jui Chuan Lin, Tsui Hsun Wu, Hsing Yuan Yen

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Pingtung County, located in the southernmost region of Taiwan, has the largest number of pig farms in the country. In the past, livestock operators in Dongpian Village discharged their wastewater into the nearby water bodies, causing water pollution in the local rivers and polluting the air with the stench of the pig excrement. These resulted in many complaints from the local residents. In response to a long time fighting back of the community against the livestock farms due to the confrict, the County Government's Environmental Protection Bureau (PTEPB) examined potential wayouts in addition to heavy fines to the perpetrators. Through helping the livestock farms to upgrade their pollution prevention equipment, promoting the reuse of biogas residue and slurry from the pig excrement, and environmental education, the confrict was successfully resolved. The properly treated wastewater from the livestock farms has been freely provided to the neighboring farmlands via pipelines and tankers. Thus, extensive cultivation of bananas, papaya, red dragon fruit, Inca nut, and cocoa has resulted in 34% resource utilization of biogas residue as a fertilizer. This has encouraged farmers to reduce chemical fertilizers and use microbial materials like photosynthetic bacteria after banning herbicides while lowering the cost of wastewater treatment in livestock farms and alleviating environmental pollution simultaneously. That is, the livestock farms fully demonstrate the determination to fulfill their corporate social responsibility (CSR). Due to the success, Eight farms jointly established a social enterprise - "Dongpian Gemstone Village Co., Ltd." to promote organic farming through a "shared farm." The company appropriates 5% of its total revenue back to the community through caregiving services for the elderly and a fund for young local farmers. The community adopted the Satoyama Initiative in accordance with the Conference of the CBD COP10. Through the positive impact of environmental education, the community seeks to realize the coexistence between society and nature while maintaining and developing socio-economic activities (including agriculture) with respect for nature and building a harmonic relationship between humans and nature. By way of sustainable management of resources and ensuring biodiversity, the community is transforming into a socio-ecological production landscape. Apart from nature conservation and watercourse ecology, preserving local culture is also a key focus of the environmental education. To mitigate the impact of global warming and climate change, the community and the government have worked together to develop a disaster prevention and relief system, strive to establish a low-carbon emitting homeland, and become a model for resilient communities. By the power of environmental education, this community has turned its residents’ hearts and minds into concrete action, fulfilled social responsibility, and moved towards realizing the UN SDGs. Even though it is not the only community to integrate government agencies, research institutions, and NGOs for environmental education, it is a prime example of a low-carbon sustainable community that achieves more than 9 SDGs, including responsible consumption and production, climate change action, and diverse partnerships. The community is also leveraging environmental education to become a net-zero carbon community targeted by COP26.

Keywords: environmental education, biogas residue, biogas slurry, CSR, SDGs, climate change, net-zero carbon emissions

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20 Pharmacophore-Based Modeling of a Series of Human Glutaminyl Cyclase Inhibitors to Identify Lead Molecules by Virtual Screening, Molecular Docking and Molecular Dynamics Simulation Study

Authors: Ankur Chaudhuri, Sibani Sen Chakraborty

Abstract:

In human, glutaminyl cyclase activity is highly abundant in neuronal and secretory tissues and is preferentially restricted to hypothalamus and pituitary. The N-terminal modification of β-amyloids (Aβs) peptides by the generation of a pyro-glutamyl (pGlu) modified Aβs (pE-Aβs) is an important process in the initiation of the formation of neurotoxic plaques in Alzheimer’s disease (AD). This process is catalyzed by glutaminyl cyclase (QC). The expression of QC is characteristically up-regulated in the early stage of AD, and the hallmark of the inhibition of QC is the prevention of the formation of pE-Aβs and plaques. A computer-aided drug design (CADD) process was employed to give an idea for the designing of potentially active compounds to understand the inhibitory potency against human glutaminyl cyclase (QC). This work elaborates the ligand-based and structure-based pharmacophore exploration of glutaminyl cyclase (QC) by using the known inhibitors. Three dimensional (3D) quantitative structure-activity relationship (QSAR) methods were applied to 154 compounds with known IC50 values. All the inhibitors were divided into two sets, training-set, and test-sets. Generally, training-set was used to build the quantitative pharmacophore model based on the principle of structural diversity, whereas the test-set was employed to evaluate the predictive ability of the pharmacophore hypotheses. A chemical feature-based pharmacophore model was generated from the known 92 training-set compounds by HypoGen module implemented in Discovery Studio 2017 R2 software package. The best hypothesis was selected (Hypo1) based upon the highest correlation coefficient (0.8906), lowest total cost (463.72), and the lowest root mean square deviation (2.24Å) values. The highest correlation coefficient value indicates greater predictive activity of the hypothesis, whereas the lower root mean square deviation signifies a small deviation of experimental activity from the predicted one. The best pharmacophore model (Hypo1) of the candidate inhibitors predicted comprised four features: two hydrogen bond acceptor, one hydrogen bond donor, and one hydrophobic feature. The Hypo1 was validated by several parameters such as test set activity prediction, cost analysis, Fischer's randomization test, leave-one-out method, and heat map of ligand profiler. The predicted features were then used for virtual screening of potential compounds from NCI, ASINEX, Maybridge and Chembridge databases. More than seven million compounds were used for this purpose. The hit compounds were filtered by drug-likeness and pharmacokinetics properties. The selective hits were docked to the high-resolution three-dimensional structure of the target protein glutaminyl cyclase (PDB ID: 2AFU/2AFW) to filter these hits further. To validate the molecular docking results, the most active compound from the dataset was selected as a reference molecule. From the density functional theory (DFT) study, ten molecules were selected based on their highest HOMO (highest occupied molecular orbitals) energy and the lowest bandgap values. Molecular dynamics simulations with explicit solvation systems of the final ten hit compounds revealed that a large number of non-covalent interactions were formed with the binding site of the human glutaminyl cyclase. It was suggested that the hit compounds reported in this study could help in future designing of potent inhibitors as leads against human glutaminyl cyclase.

Keywords: glutaminyl cyclase, hit lead, pharmacophore model, simulation

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19 Development of Anti-Fouling Surface Features Bioinspired by the Patterned Micro-Textures of the Scophthalmus rhombus (Brill)

Authors: Ivan Maguire, Alan Barrett, Alex Forte, Sandra Kwiatkowska, Rohit Mishra, Jens Ducrèe, Fiona Regan

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Biofouling is defined as the gradual accumulation of Biomimetics refers to the use and imitation of principles copied from nature. Biomimetics has found interest across many commercial disciplines. Among many biological objects and their functions, aquatic animals deserve a special attention due to their antimicrobial capabilities resulting from chemical composition, surface topography or other behavioural defences, which can be used as an inspiration for antifouling technology. Marine biofouling has detrimental effects on seagoing vessels, both commercial and leisure, as well as on oceanographic sensors, offshore drilling rigs, and aquaculture installations. Sensor optics, membranes, housings and platforms can become fouled leading to problems with sensor performance and data integrity. While many anti-fouling solutions are currently being investigated as a cost-cutting measure, biofouling settlement may also be prevented by creating a surface that does not satisfy the settlement conditions. Brill (Scophthalmus rhombus) is a small flatfish occurring in marine waters of Mediterranean as well as Norway and Iceland. It inhabits sandy and muddy coastal waters from 5 to 80 meters. Its skin colour changes depending on environment, but generally is brownish with light and dark freckles, with creamy underside. Brill is oval in shape and its flesh is white. The aim of this study is to translate the unique micro-topography of the brill scale, to design marine inspired biomimetic surface coating and test it against a typical fouling organism. Following extensive study of scale topography of the brill fish (Scophthalmus rhombus) and the settlement behaviour of the diatom species Psammodictyon sp. via SEM, two state-of-the-art antifouling surface solutions were designed and investigated; A brill fish scale bioinspired surface pattern platform (BFD), and generic and uniformly-arrayed, circular micropillar platform (MPD), with offsets based on diatom species settlement behaviour. The BFD approach consists of different ~5 μm by ~90 μm Brill-replica patterns, grown to a 5 μm height, in a linear array pattern. The MPD approach utilises hexagonal-packed cylindrical pillars 10.6 μm in diameter, grown to a height of 5 μm, with vertical offset of 15 μm and horizontal offset of 26.6 μm. Photolithography was employed for microstructure growth, with a polydimethylsiloxane (PDMS) chip-based used as a testbed for diatom adhesion on both platforms. Settlement and adhesion tests were performed using this PDMS microfluidic chip through subjugation to centrifugal force via an in-house developed ‘spin-stand’ which features a motor, in combination with a high-resolution camera, for real-time observing diatom release from PDMS material. Diatom adhesion strength can therefore be determined based on the centrifugal force generated at varying rotational speeds. It is hoped that both the replica and bio-inspired solutions will give comparable anti-fouling results to these synthetic surfaces, whilst also assisting in determining whether anti-fouling solutions should predominantly be investigating either fully bioreplica-based, or a bioinspired, synthetically-based design.

Keywords: anti-fouling applications, bio-inspired microstructures, centrifugal microfluidics, surface modification

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18 Physico-Chemical Characterization of Vegetable Oils from Oleaginous Seeds (Croton megalocarpus, Ricinus communis L., and Gossypium hirsutum L.)

Authors: Patrizia Firmani, Sara Perucchini, Irene Rapone, Raffella Borrelli, Stefano Chiaberge, Manuela Grande, Rosamaria Marrazzo, Alberto Savoini, Andrea Siviero, Silvia Spera, Fabio Vago, Davide Deriu, Sergio Fanutti, Alessandro Oldani

Abstract:

According to the Renewable Energy Directive II, the use of palm oil in diesel will be gradually reduced from 2023 and should reach zero in 2030 due to the deforestation caused by its production. Eni aims at finding alternative feedstocks for its biorefineries to eliminate the use of palm oil by 2023. Therefore, the ideal vegetable oils to be used in bio-refineries are those obtainable from plants that grow in marginal lands and with low impact on food-and-feed chain; hence, Eni research is studying the possibility of using oleaginous seeds, such as castor, croton, and cotton, to extract the oils to be exploited as feedstock in bio-refineries. To verify their suitability for the upgrading processes, an analytical protocol for their characterization has been drawn up and applied. The analytical characterizations include a step of water and ashes content determination, elemental analysis (CHNS analysis, X-Ray Fluorescence, Inductively Coupled Plasma - Optical Emission Spectroscopy, ICP– Mass Spectrometry), and total acid number determination. Gas chromatography coupled to flame ionization detector (GC-FID) is used to quantify the lipid content in terms of free fatty acids, mono-, di- and triacylglycerols, and fatty acids composition. Eventually, Nuclear Magnetic Resonance and Fourier Transform-Infrared spectroscopies are exploited with GC-MS and Fourier Transform-Ion Cyclotron Resonance to study the composition of the oils. This work focuses on the GC-FID analysis of the lipid fraction of these oils, as the main constituent and of greatest interest for bio-refinery processes. Specifically, the lipid component of the extracted oil was quantified after sample silanization and transmethylation: silanization allows the elution of high-boiling compounds and is useful for determining the quantity of free acids and glycerides in oils, while transmethylation leads to a mixture of fatty acid esters and glycerol, thus allowing to evaluate the composition of glycerides in terms of Fatty Acids Methyl Esters (FAME). Cotton oil was extracted from cotton oilcake, croton oil was obtained by seeds pressing and seeds and oilcake ASE extraction, while castor oil comes from seed pressing (not performed in Eni laboratories). GC-FID analyses reported that the cotton oil is 90% constituted of triglycerides and about 6% diglycerides, while free fatty acids are about 2%. In terms of FAME, C18 acids make up 70% of the total and linoleic acid is the major constituent. Palmitic acid is present at 17.5%, while the other acids are in low concentration (<1%). Both analyzes show the presence of non-gas chromatographable compounds. Croton oils from seed pressing and extraction mainly contain triglycerides (98%). Concerning FAME, the main component is linoleic acid (approx. 80%). Oilcake croton oil shows higher abundance of diglycerides (6% vs ca 2%) and a lower content of triglycerides (38% vs 98%) compared to the previous oils. Eventually, castor oil is mostly constituted of triacylglycerols (about 69%), followed by diglycerides (about 10%). About 85.2% of total FAME is ricinoleic acid, as a constituent of triricinolein, the most abundant triglyceride of castor oil. Based on the analytical results, these oils represent feedstocks of interest for possible exploitation as advanced biofuels.

Keywords: analytical protocol, biofuels, biorefinery, gas chromatography, vegetable oil

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17 Oxidation Behavior of Ferritic Stainless Steel Interconnects Modified Using Nanoparticles of Rare-Earth Elements under Operating Conditions Specific to Solid Oxide Electrolyzer Cells

Authors: Łukasz Mazur, Kamil Domaradzki, Bartosz Kamecki, Justyna Ignaczak, Sebastian Molin, Aleksander Gil, Tomasz Brylewski

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The rising global power consumption necessitates the development of new energy storage solutions. Prospective technologies include solid oxide electrolyzer cells (SOECs), which convert surplus electrical energy into hydrogen. An electrolyzer cell consists of a porous anode, and cathode, and a dense electrolyte. Power output is increased by connecting cells into stacks using interconnects. Interconnects are currently made from high-chromium ferritic steels – for example, Crofer 22 APU – which exhibit high oxidation resistance and a thermal expansion coefficient that is similar to that of electrode materials. These materials have one disadvantage – their area-specific resistance (ASR) gradually increases due to the formation of a Cr₂O₃ scale on their surface as a result of oxidation. The chromia in the scale also reacts with the water vapor present in the reaction media, forming volatile chromium oxyhydroxides, which in turn react with electrode materials and cause their deterioration. The electrochemical efficiency of SOECs thus decreases. To mitigate this, the interconnect surface can be modified with protective-conducting coatings of spinel or other materials. The high prices of SOEC components -especially the Crofer 22 APU- have prevented their widespread adoption. More inexpensive counterparts, therefore, need to be found, and their properties need to be enhanced to make them viable. Candidates include the Nirosta 4016/1,4016 low-chromium ferritic steel with a chromium content of just 16.3 wt%. This steel's resistance to high-temperature oxidation was improved by depositing Gd₂O₃ nanoparticles on its surface via either dip coating or electrolysis. Modification with CeO₂ or Ce₀.₉Y₀.₁O₂ nanoparticles deposited by means of spray pyrolysis was also tested. These methods were selected because of their low cost and simplicity of application. The aim of this study was to investigate the oxidation kinetics of Nirosta 4016/1,4016 modified using the afore-mentioned methods and to subsequently measure the obtained samples' ASR. The samples were oxidized for 100 h in the air as well as air/H₂O and Ar/H₂/H₂O mixtures at 1073 K. Such conditions reflect those found in the anode and cathode operating space during real-life use of SOECs. Phase and chemical composition and the microstructure of oxidation products were determined using XRD and SEM-EDS. ASR was measured over the range of 623-1073 K using a four-point, two-probe DC technique. The results indicate that the applied nanoparticles improve the oxidation resistance and electrical properties of the studied layered systems. The properties of individual systems varied significantly depending on the applied reaction medium. Gd₂O₃ nanoparticles improved oxidation resistance to a greater degree than either CeO₂ or Ce₀.₉Y₀.₁O₂ nanoparticles. On the other hand, the cerium-containing nanoparticles improved electrical properties regardless of the reaction medium. The ASR values of all surface-modified steel samples were below the 0.1 Ω.cm² threshold set for interconnect materials, which was exceeded in the case of the unmodified reference sample. It can be concluded that the applied modifications increased the oxidation resistance of Nirosta 4016/1.4016 to a level that allows its use as SOEC interconnect material. Acknowledgments: Funding of Research project supported by program "Excellence initiative – research university" for the AGH University of Krakow" is gratefully acknowledged (TB).

Keywords: cerium oxide, ferritic stainless steel, gadolinium oxide, interconnect, SOEC

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16 Anti-Infective Potential of Selected Philippine Medicinal Plant Extracts against Multidrug-Resistant Bacteria

Authors: Demetrio L. Valle Jr., Juliana Janet M. Puzon, Windell L. Rivera

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From the various medicinal plants available in the Philippines, crude ethanol extracts of twelve (12) Philippine medicinal plants, namely: Senna alata L. Roxb. (akapulko), Psidium guajava L. (bayabas), Piper betle L. (ikmo), Vitex negundo L. (lagundi), Mitrephora lanotan (Blanco) Merr. (Lanotan), Zingiber officinale Roscoe (luya), Curcuma longa L. (Luyang dilaw), Tinospora rumphii Boerl (Makabuhay), Moringga oleifera Lam. (malunggay), Phyllanthus niruri L. (sampa-sampalukan), Centella asiatica (L.) Urban (takip kuhol), and Carmona retusa (Vahl) Masam (tsaang gubat) were studied. In vitro methods of evaluation against selected Gram-positive and Gram-negative multidrug-resistant (MDR), bacteria were performed on the plant extracts. Although five of the plants showed varying antagonistic activities against the test organisms, only Piper betle L. exhibited significant activities against both Gram-negative and Gram-positive multidrug-resistant bacteria, exhibiting wide zones of growth inhibition in the disk diffusion assay, and with the lowest concentrations of the extract required to inhibit the growth of the bacteria, as supported by the minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) assays. Further antibacterial studies of the Piper betle L. leaf, obtained by three extraction methods (ethanol, methanol, supercritical CO2), revealed similar inhibitory activities against a multitude of Gram-positive and Gram-negative MDR bacteria. Thin layer chromatography (TLC) assay of the leaf extract revealed a maximum of eight compounds with Rf values of 0.92, 0.86, 0.76, 0.53, 0.40, 0.25, 0.13, and 0.013, best visualized when inspected under UV-366 nm. TLC- agar overlay bioautography of the isolated compounds showed the compounds with Rf values of 0.86 and 0.13 having inhibitory activities against Gram-positive MDR bacteria (MRSA and VRE). The compound with an Rf value of 0.86 also possesses inhibitory activity against Gram-negative MDR bacteria (CRE Klebsiella pneumoniae and MBL Acinetobacter baumannii). Gas Chromatography-Mass Spectrometry (GC-MS) was able to identify six volatile compounds, four of which are new compounds that have not been mentioned in the medical literature. The chemical compounds isolated include 4-(2-propenyl)phenol and eugenol; and the new four compounds were ethyl diazoacetate, tris(trifluoromethyl)phosphine, heptafluorobutyrate, and 3-fluoro-2-propynenitrite. Phytochemical screening and investigation of its antioxidant, cytotoxic, possible hemolytic activities, and mechanisms of antibacterial activity were also done. The results showed that the local variant of Piper betle leaf extract possesses significant antioxidant, anti-cancer and antimicrobial properties, attributed to the presence of bioactive compounds, particularly of flavonoids (condensed tannin, leucoanthocyanin, gamma benzopyrone), anthraquinones, steroids/triterpenes and 2-deoxysugars. Piper betle L. is also traditionally known to enhance wound healing, which could be primarily due to its antioxidant, anti-inflammatory and antimicrobial activities. In vivo studies on mice using 2.5% and 5% of the ethanol leaf extract cream formulations in the excised wound models significantly increased the process of wound healing in the mice subjects, the results and values of which are at par with the current antibacterial cream (Mupirocin). From the results of the series of studies, we have definitely proven the value of Piper betle L. as a source of bioactive compounds that could be developed into therapeutic agents against MDR bacteria.

Keywords: Philippine herbal medicine, multidrug-resistant bacteria, Piper betle, TLC-bioautography

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15 [Keynote Talk]: Bioactive Cyclic Dipeptides of Microbial Origin in Discovery of Cytokine Inhibitors

Authors: Sajeli A. Begum, Ameer Basha, Kirti Hira, Rukaiyya Khan

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Cyclic dipeptides are simple diketopiperazine derivatives being investigated by several scientists for their biological effects which include anticancer, antimicrobial, haematological, anticonvulsant, immunomodulatory effect, etc. They are potentially active microbial metabolites having been synthesized too, for developing into drug candidates. Cultures of Pseudomonas species have earlier been reported to produce cyclic dipeptides, helping in quorum sensing signals and bacterial–host colonization phenomena during infections, causing cell anti-proliferation and immunosuppression. Fluorescing Pseudomonas species have been identified to secrete lipid derivatives, peptides, pyrroles, phenazines, indoles, aminoacids, pterines, pseudomonic acids and some antibiotics. In the present work, results of investigation on the cyclic dipeptide metabolites secreted by the culture broth of Pseudomonas species as potent pro-inflammatory cytokine inhibitors are discussed. The bacterial strain was isolated from the rhizospheric soil of groundnut crop and identified as Pseudomonas aeruginosa by 16S rDNA sequence (GenBank Accession No. KT625586). Culture broth of this strain was prepared by inoculating into King’s B broth and incubating at 30 ºC for 7 days. The ethyl acetate extract of culture broth was prepared and lyophilized to get a dry residue (EEPA). Lipopolysaccharide (LPS)-induced ELISA assay proved the inhibition of tumor necrosis factor-alpha (TNF-α) secretion in culture supernatant of RAW 264.7 cells by EEPA (IC50 38.8 μg/mL). The effect of oral administration of EEPA on plasma TNF-α level in rats was tested by ELISA kit. The LPS mediated plasma TNF-α level was reduced to 45% with 125 mg/kg dose of EEPA. Isolation of the chemical constituents of EEPA through column chromatography yielded ten cyclic dipeptides, which were characterized using nuclear magnetic resonance and mass spectroscopic techniques. These cyclic dipeptides are biosynthesized in microorganisms by multifunctional assembly of non-ribosomal peptide synthases and cyclic dipeptide synthase. Cyclo (Gly-L-Pro) was found to be more potentially (IC50 value 4.5 μg/mL) inhibiting TNF-α production followed by cyclo (trans-4-hydroxy-L-Pro-L-Phe) (IC50 value 14.2 μg/mL) and the effect was equal to that of standard immunosuppressant drug, prednisolone. Further, the effect was analyzed by determining mRNA expression of TNF-α in LPS-stimulated RAW 264.7 macrophages using quantitative real-time reverse transcription polymerase chain reaction. EEPA and isolated cyclic dipeptides demonstrated diminution of TNF-α mRNA expression levels in a dose-dependent manner under the tested conditions. Also, they were found to control the expression of other pro-inflammatory cytokines like IL-1β and IL-6, when tested through their mRNA expression levels in LPS-stimulated RAW 264.7 macrophages under LPS-stimulated conditions. In addition, significant inhibition effect was found on Nitric oxide production. Further all the compounds exhibited weak toxicity to LPS-induced RAW 264.7 cells. Thus the outcome of the study disclosed the effectiveness of EEPA and the isolated cyclic dipeptides in down-regulating key cytokines involved in pathophysiology of autoimmune diseases.In another study led by the investigators, microbial cyclic dipeptides were found to exhibit excellent antimicrobial effect against Fusarium moniliforme which is an important causative agent of Sorghum grain mold disease. Thus, cyclic dipeptides are emerging small molecular drug candidates for various autoimmune diseases.

Keywords: cyclic dipeptides, cytokines, Fusarium moniliforme, Pseudomonas, TNF-alpha

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14 Sampling and Chemical Characterization of Particulate Matter in a Platinum Mine

Authors: Juergen Orasche, Vesta Kohlmeier, George C. Dragan, Gert Jakobi, Patricia Forbes, Ralf Zimmermann

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Underground mining poses a difficult environment for both man and machines. At more than 1000 meters underneath the surface of the earth, ores and other mineral resources are still gained by conventional and motorised mining. Adding to the hazards caused by blasting and stone-chipping, the working conditions are best described by the high temperatures of 35-40°C and high humidity, at low air exchange rates. Separate ventilation shafts lead fresh air into a mine and others lead expended air back to the surface. This is essential for humans and machines working deep underground. Nevertheless, mines are widely ramified. Thus the air flow rate at the far end of a tunnel is sensed to be close to zero. In recent years, conventional mining was supplemented by mining with heavy diesel machines. These very flat machines called Load Haul Dump (LHD) vehicles accelerate and ease work in areas favourable for heavy machines. On the other hand, they emit non-filtered diesel exhaust, which constitutes an occupational hazard for the miners. Combined with a low air exchange, high humidity and inorganic dust from the mining it leads to 'black smog' underneath the earth. This work focuses on the air quality in mines employing LHDs. Therefore we performed personal sampling (samplers worn by miners during their work), stationary sampling and aethalometer (Microaeth MA200, Aethlabs) measurements in a platinum mine in around 1000 meters under the earth’s surface. We compared areas of high diesel exhaust emission with areas of conventional mining where no diesel machines were operated. For a better assessment of health risks caused by air pollution we applied a separated gas-/particle-sampling tool (or system), with first denuder section collecting intermediate VOCs. These multi-channel silicone rubber denuders are able to trap IVOCs while allowing particles ranged from 10 nm to 1 µm in diameter to be transmitted with an efficiency of nearly 100%. The second section is represented by a quartz fibre filter collecting particles and adsorbed semi-volatile organic compounds (SVOC). The third part is a graphitized carbon black adsorber – collecting the SVOCs that evaporate from the filter. The compounds collected on these three sections were analyzed in our labs with different thermal desorption techniques coupled with gas chromatography and mass spectrometry (GC-MS). VOCs and IVOCs were measured with a Shimadzu Thermal Desorption Unit (TD20, Shimadzu, Japan) coupled to a GCMS-System QP 2010 Ultra with a quadrupole mass spectrometer (Shimadzu). The GC was equipped with a 30m, BP-20 wax column (0.25mm ID, 0.25µm film) from SGE (Australia). Filters were analyzed with In-situ derivatization thermal desorption gas chromatography time-of-flight-mass spectrometry (IDTD-GC-TOF-MS). The IDTD unit is a modified GL sciences Optic 3 system (GL Sciences, Netherlands). The results showed black carbon concentrations measured with the portable aethalometers up to several mg per m³. The organic chemistry was dominated by very high concentrations of alkanes. Typical diesel engine exhaust markers like alkylated polycyclic aromatic hydrocarbons were detected as well as typical lubrication oil markers like hopanes.

Keywords: diesel emission, personal sampling, aethalometer, mining

Procedia PDF Downloads 157
13 Optical Coherence Tomography in Differentiation of Acute and Non-Healing Wounds

Authors: Ananya Barui, Provas Banerjee, Jyotirmoy Chatterjee

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Application of optical technology in medicine and biology has a long track-record. In this endeavor, OCT is able to attract both engineers and biologists to work together in the field of photonics for establishing a striking non-invasive imaging technology. In contrast to other in vivo imaging modalities like Raman imaging, confocal imaging, two-photon microscopy etc. which can perform in vivo imaging upto 100-200 micron depth due to limitation in numerical aperture or scattering, however, OCT can achieve high-resolution imaging upto few millimeters of tissue structures depending on their refractive index in different anatomical location. This tomographic system depends on interference of two light waves in an interferometer to produce a depth profile of specimen. In wound healing, frequent collection of biopsies for follow-up of repair process could be avoided by such imaging technique. Real time skin OCT (the optical biopsy) has efficacy in deeper and faster illumination of cutaneou tissue to acquire high resolution cross sectional images of their internal micro-structure. Swept Source-OCT (SS-OCT), a novel imaging technique, can generate high-speed depth profile (~ 2 mm) of wound at a sweeping rate of laser with micron level resolution and optimum coherent length of 5-6 mm. Normally multi-layered skin tissue depicts different optical properties along with variation in thickness, refractive index and composition (i.e. keratine layer, water, fat etc.) according to their anatomical location. For instance, stratum corneum, the upper-most and relatively dehydrated layer of epidermis reflects more light and produces more lucid and a sharp demarcation line with rest of the hydrated epidermal region. During wound healing or regeneration, optical properties of cutaneous tissue continuously altered with maturation of wound bed. More mature and less hydrated tissue component reflects more light and becomes visible as a brighter area in comparison to immature region which content higher amount water or fat that depicts as a darker area in OCT image. Non-healing wound possess prolonged inflammation and inhibits nascent proliferative stage. Accumulation of necrotic tissues also prevents the repair of non-healing wounds. Due to high resolution and potentiality to reflect the compositional aspects of tissues in terms of their optical properties, this tomographic method may facilitate in differentiating non-healing and acute wounds in addition to clinical observations. Non-invasive OCT offers better insight regarding specific biological status of tissue in health and pathological conditions, OCT images could be associated with histo-pathological ‘gold standard’. This correlated SS-OCT and microscopic evaluation of the wound edges can provide information regarding progressive healing and maturation of the epithelial components. In the context of searching analogy between two different imaging modalities, their relative performances in imaging of healing bed were estimated for probing an alternative approach. Present study validated utility of SS-OCT in revealing micro-anatomic structure in the healing bed with newer information. Exploring precise correspondence of OCT images features with histo-chemical findings related to epithelial integrity of the regenerated tissue could have great implication. It could establish the ‘optical biopsy’ as a potent non-invasive diagnostic tool for cutaneous pathology.

Keywords: histo-pathology, non invasive imaging, OCT, wound healing

Procedia PDF Downloads 279
12 Microbes at Work: An Assessment on the Use of Microbial Inoculants in Reforestation and Rehabilitation of the Forest Ancestral Land of Magbukun Aytas of Morong, Bataan, Philippines

Authors: Harold M. Carag, April Charmaine D. Camacho, Girlie Nora A. Abrigo, Florencia G. Palis, Ma. Larissa Lelu P. Gata

Abstract:

A technology impact assessment on the use of microbial inoculants in the reforestation and rehabilitation of forest ancestral lands of the Magbukün Aytas in Morong, Bataan was conducted. This two-year rainforestation technology aimed to determine the optimum condition for the improvement of seedling survival rate in the nursery and in the field to hasten the process of forest regeneration of Magbukün Ayta’s ancestral land. A combination of qualitative methods (key informant interviews, focus groups and participant observation), participated by the farmers who were directly involved in the project, community men and women, the council of elders and the project staff, was employed to complete this impact assessment. The recorded data were transcribed, and the accounts were broadly categorized on the following aspects: social (gender, institutional, anthropological), economic and environmental. The Australian Center for International Agricultural Research (ACIAR) framework was primarily used for the impact analysis while the Harvard Analytical Framework was specifically used for the gender impact analysis. Through this technology, a wildling nursery with more than one thousand seedlings was successfully established and served as a good area for the healthy growth of seedlings that would be planted in the forest. Results showed that this technology affected positively and negatively the various gender roles present in the community although household work remained to be the women’s responsibility. The technology introduced directly added up to the workload done by the men and women (preparing and applying fertilizer, making pots etc.) but this, in turn, provided ways to increase their sources of livelihood. The gender roles that were already present were further strengthened after the project and men remained to be in control. The technology or project in turn also benefited from the already present roles since they no longer have to assign things to them, the execution of the various roles was smoothly executed. In the anthropological aspect, their assigned task to manage the nursery was an easy responsibility because of their deep connection to the environment and their fear and beliefs on ‘engkato’ and ‘anito’ was helpful in guarding the forest. As the cultural value of these trees increases, their mindset of safeguarding the forest also heightens. Meanwhile, the welfare of the whole tribe is the ultimate determinant of the swift entry of projects. The past institutions brought ephemeral reliefs on the subsistence of the Magbukün Aytas. These were good ‘conditioning’ factors for the adoption of the technology of the project. As an attempt to turn away from the dependent of harmful chemical, the project’s way of introducing organic inputs was slowly gaining popularity in the community. Economically, the project was able to provide additional income to the farmers. However, the slow mode of payment dismayed other farmers and abandoned their roles. Lastly, major environmental effects weren’t that much observed after the application of the technology. The minor effects concentrated more on the improved conditions of the soil and water in the community. Because of the introduced technology, soil conditions became more favorable specifically for the species that were planted. The organic fertilizers used were in turn not harmful for the residents living in Sitio Kanawan. There were no human diseases caused by the technology. The conservation of the biodiversity of the forest is clearly the most evident long-term result of the project.

Keywords: ancestral lands, impact assessment, microbial inculants, reforestation

Procedia PDF Downloads 142
11 Interference of Polymers Addition in Wastewaters Microbial Survey: Case Study of Viral Retention in Sludges

Authors: Doriane Delafosse, Dominique Fontvieille

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Background: Wastewater treatment plants (WWTPs) generally display significant efficacy in virus retention yet, are sometimes highly variable, partly in relation to large fluctuating loads at the head of the plant and partly because of episodic dysfunctions in some treatment processes. The problem is especially sensitive when human enteric viruses, such as human Noroviruses Genogroup I or Adenoviruses, are in concern: their release downstream WWTP, in environments often interconnected to recreational areas, may be very harmful to human communities even at low concentrations. It points out the importance of WWTP permanent monitoring from which their internal treatment processes could be adjusted. One way to adjust primary treatments is to add coagulants and flocculants to sewage ahead settling tanks to improve decantation. In this work, sludge produced by three coagulants (two organics, one mineral), four flocculants (three cationic, one anionic), and their combinations were studied for their efficacy in human enteric virus retention. Sewage samples were coming from a WWTP in the vicinity of the laboratory. All experiments were performed three times and in triplicates in laboratory pilots, using Murine Norovirus (MNV-1), a surrogate of human Norovirus, as an internal control (spiking). Viruses were quantified by (RT-)qPCR after nucleic acid extraction from both treated water and sediment. Results: Low values of sludge virus retention (from 4 to 8% of the initial sewage concentration) were observed with each cationic organic flocculant added to wastewater and no coagulant. The largest part of the virus load was detected in the treated water (48 to 90%). However, it was not counterbalancing the amount of the introduced virus (MNV-1). The results pertained to two types of cationic flocculants, branched and linear, and in the last case, to two percentages of cations. Results were quite similar to the association of a linear cationic organic coagulant and an anionic flocculant, though suggesting that differences between water and sludges would sometimes be related to virus size or virus origins (autochthonous/allochthonous). FeCl₃, as a mineral coagulant associated with an anionic flocculant, significantly increased both auto- and allochthonous virus retention in the sediments (15 to 34%). Accordingly, virus load in treated water was lower (14 to 48%) but with a total that still does not reach the amount of the introduced virus (MNV-1). It also appeared that the virus retrieval in a bare 0.1M NaCl suspension varied rather strongly according to the FeCl₃ concentration, suggesting an inhibiting effect on the molecular analysis used to detect the virus. Finally, no viruses were detected in both phases (sediment and water) with the combination branched cationic coagulant-linear anionic flocculant, which was later demonstrated as an effect, here also, of polymers on the virus detection-molecular analysis. Conclusions: The combination of FeCl₃-anionic flocculant gave its highest performance to the decantation-based virus removal process. However, large unbalanced values in spiking experiments were observed, suggesting that polymers cast additional obstacles to both elution buffer and lysis buffer on their way to reach the virus. The situation was probably even worse with autochthonous viruses already embedded into sewage's particulate matter. Polymers and FeCl₃ also appeared to interfere in some steps of molecular analyses. More attention should be paid to such impediments wherever chemical additives are considered to be used to enhance WWTP processes. Acknowledgments: This research was supported by the ABIOLAB laboratory (Montbonnot Saint-Martin, France) and by the ASPOSAN association. Field experiments were possible thanks to the Grand Chambéry WWTP authorities (Chambéry, France).

Keywords: flocculants-coagulants, polymers, enteric viruses, wastewater sedimentation treatment plant

Procedia PDF Downloads 124
10 From Linear to Circular Model: An Artificial Intelligence-Powered Approach in Fosso Imperatore

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

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— 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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9 Characterization of Aluminosilicates and Verification of Their Impact on Quality of Ceramic Proppants Intended for Shale Gas Output

Authors: Joanna Szymanska, Paulina Wawulska-Marek, Jaroslaw Mizera

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Nowadays, the rapid growth of global energy consumption and uncontrolled depletion of natural resources become a serious problem. Shale rocks are the largest and potential global basins containing hydrocarbons, trapped in closed pores of the shale matrix. Regardless of the shales origin, mining conditions are extremely unfavourable due to high reservoir pressure, great depths, increased clay minerals content and limited permeability (nanoDarcy) of the rocks. Taking into consideration such geomechanical barriers, effective extraction of natural gas from shales with plastic zones demands effective operations. Actually, hydraulic fracturing is the most developed technique based on the injection of pressurized fluid into a wellbore, to initiate fractures propagation. However, a rapid drop of pressure after fluid suction to the ground induces a fracture closure and conductivity reduction. In order to minimize this risk, proppants should be applied. They are solid granules transported with hydraulic fluids to locate inside the rock. Proppants act as a prop for the closing fracture, thus gas migration to a borehole is effective. Quartz sands are commonly applied proppants only at shallow deposits (USA). Whereas, ceramic proppants are designed to meet rigorous downhole conditions to intensify output. Ceramic granules predominate with higher mechanical strength, stability in strong acidic environment, spherical shape and homogeneity as well. Quality of ceramic proppants is conditioned by raw materials selection. Aim of this study was to obtain the proppants from aluminosilicates (the kaolinite subgroup) and mix of minerals with a high alumina content. These loamy minerals contain a tubular and platy morphology that improves mechanical properties and reduces their specific weight. Moreover, they are distinguished by well-developed surface area, high porosity, fine particle size, superb dispersion and nontoxic properties - very crucial for particles consolidation into spherical and crush-resistant granules in mechanical granulation process. The aluminosilicates were mixed with water and natural organic binder to improve liquid-bridges and pores formation between particles. Afterward, the green proppants were subjected to sintering at high temperatures. Evaluation of the minerals utility was based on their particle size distribution (laser diffraction study) and thermal stability (thermogravimetry). Scanning Electron Microscopy was useful for morphology and shape identification combined with specific surface area measurement (BET). Chemical composition was verified by Energy Dispersive Spectroscopy and X-ray Fluorescence. Moreover, bulk density and specific weight were measured. Such comprehensive characterization of loamy materials confirmed their favourable impact on the proppants granulation. The sintered granules were analyzed by SEM to verify the surface topography and phase transitions after sintering. Pores distribution was identified by X-Ray Tomography. This method enabled also the simulation of proppants settlement in a fracture, while measurement of bulk density was essential to predict their amount to fill a well. Roundness coefficient was also evaluated, whereas impact on mining environment was identified by turbidity and solubility in acid - to indicate risk of the material decay in a well. The obtained outcomes confirmed a positive influence of the loamy minerals on ceramic proppants properties with respect to the strict norms. This research is perspective for higher quality proppants production with costs reduction.

Keywords: aluminosilicates, ceramic proppants, mechanical granulation, shale gas

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8 SockGEL/PLUG: Injectable Nano-Scaled Hydrogel Platforms for Oral and Maxillofacial Interventional Application

Authors: Z. S. Haidar

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Millions of teeth are removed annually, and dental extraction is one of the most commonly performed surgical procedures globally. Whether due to caries, periodontal disease, or trauma, exodontia and the ensuing wound healing and bone remodeling processes of the resultant socket (hole in the jaw bone) usually result in serious deformities of the residual alveolar osseous ridge and surrounding soft tissues (reduced height/width). Such voluminous changes render the placement of a proper conventional bridge, denture, or even an implant-supported prosthesis extremely challenging. Further, most extractions continue to be performed with no regard for preventing the onset of alveolar osteitis (also known as dry socket, a painful and difficult-to-treat/-manage condition post-exodontia). Hence, such serious resorptive morphological changes often result in significant facial deformities and a negative impact on the overall Quality of Life (QoL) of patients (and oral health-related QoL); alarming, particularly for the geriatric with compromised healing and in light of the thriving longevity statistics. Despite advances in tissue/wound grafting, serious limitations continue to exist, including efficacy and clinical outcome predictability, cost, treatment time, expertise, and risk of immune reactions. For cases of dry socket, specifically, the commercially available and often-prescribed home remedies are highly-lacking. Indeed, most are not recommended for use anymore. Alveogyl is a fine example. Hence, there is a great market demand and need for alternative solutions. Herein, SockGEL/PLUG (patent pending), an innovative, all-natural, drug-free, and injectable thermo-responsive hydrogel, was designed, formulated, characterized, and evaluated as an osteogenic, angiogenic, anti-microbial, and pain-soothing suture-free intra-alveolar dressing, safe and efficacious for use in fresh extraction sockets, immediately post-exodontia. It is composed of FDA-approved, biocompatible and biodegradable polymers, self-assembled electro-statically to formulate a scaffolding matrix to (1) prevent the on-set of alveolar osteitis via securing the fibrin-clot in situ and protecting/sealing the socket from contamination/infection; and (2) endogenously promote/accelerate wound healing and bone remodeling to preserve the volume of the alveolus. The intrinsic properties of the SockGEL/PLUG hydrogel were evaluated physical-chemical-mechanically for safety (cell viability), viscosity, rheology, bio-distribution, and essentially, capacity to induce wound healing and osteogenesis (small defect, in vivo) without any signaling cues from exogenous cells, growth factors or drugs. The proposed animal model of cranial critical-sized and non-vascularized bone defects shall provide new and critical insights into the role and mechanism of the employed natural bio-polymer blend and gel product in endogenous reparative regeneration of soft tissues and bone morphogenesis. Alongside, the fine-tuning of our modified formulation method will further tackle appropriateness, reproducibility, scalability, ease, and speed in producing stable, biodegradable, and sterilizable thermo-sensitive matrices (3-dimensional interpenetrating yet porous polymeric network) suitable for the intra-socket application. Findings are anticipated to provide sufficient evidence to translate into pilot clinical trials and validate the innovation before engaging the market for feasibility, acceptance, and cost-effectiveness studies.

Keywords: hydrogel, nanotechnology, bioengineering, bone regeneration, nanogel, drug delivery

Procedia PDF Downloads 111
7 Light Sensitive Plasmonic Nanostructures for Photonic Applications

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

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6 Surface Acoustic Wave (SAW)-Induced Mixing Enhances Biomolecules Kinetics in a Novel Phase-Interrogation Surface Plasmon Resonance (SPR) Microfluidic Biosensor

Authors: M. Agostini, A. Sonato, G. Greco, M. Travagliati, G. Ruffato, E. Gazzola, D. Liuni, F. Romanato, M. Cecchini

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Since their first demonstration in the early 1980s, surface plasmon resonance (SPR) sensors have been widely recognized as useful tools for detecting chemical and biological species, and the interest of the scientific community toward this technology has known a rapid growth in the past two decades owing to their high sensitivity, label-free operation and possibility of real-time detection. Recent works have suggested that a turning point in SPR sensor research would be the combination of SPR strategies with other technologies in order to reduce human handling of samples, improve integration and plasmonic sensitivity. In this light, microfluidics has been attracting growing interest. By properly designing microfluidic biochips it is possible to miniaturize the analyte-sensitive areas with an overall reduction of the chip dimension, reduce the liquid reagents and sample volume, improve automation, and increase the number of experiments in a single biochip by multiplexing approaches. However, as the fluidic channel dimensions approach the micron scale, laminar flows become dominant owing to the low Reynolds numbers that typically characterize microfluidics. In these environments mixing times are usually dominated by diffusion, which can be prohibitively long and lead to long-lasting biochemistry experiments. An elegant method to overcome these issues is to actively perturb the liquid laminar flow by exploiting surface acoustic waves (SAWs). With this work, we demonstrate a new approach for SPR biosensing based on the combination of microfluidics, SAW-induced mixing and the real-time phase-interrogation grating-coupling SPR technology. On a single lithium niobate (LN) substrate the nanostructured SPR sensing areas, interdigital transducer (IDT) for SAW generation and polydimethylsiloxane (PDMS) microfluidic chambers were fabricated. SAWs, impinging on the microfluidic chamber, generate acoustic streaming inside the fluid, leading to chaotic advection and thus improved fluid mixing, whilst analytes binding detection is made via SPR method based on SPP excitation via gold metallic grating upon azimuthal orientation and phase interrogation. Our device has been fully characterized in order to separate for the very first time the unwanted SAW heating effect with respect to the fluid stirring inside the microchamber that affect the molecules binding dynamics. Avidin/biotin assay and thiol-polyethylene glycol (bPEG-SH) were exploited as model biological interaction and non-fouling layer respectively. Biosensing kinetics time reduction with SAW-enhanced mixing resulted in a ≈ 82% improvement for bPEG-SH adsorption onto gold and ≈ 24% for avidin/biotin binding—≈ 50% and 18% respectively compared to the heating only condition. These results demonstrate that our biochip can significantly reduce the duration of bioreactions that usually require long times (e.g., PEG-based sensing layer, low concentration analyte detection). The sensing architecture here proposed represents a new promising technology satisfying the major biosensing requirements: scalability and high throughput capabilities. The detection system size and biochip dimension could be further reduced and integrated; in addition, the possibility of reducing biological experiment duration via SAW-driven active mixing and developing multiplexing platforms for parallel real-time sensing could be easily combined. In general, the technology reported in this study can be straightforwardly adapted to a great number of biological system and sensing geometry.

Keywords: biosensor, microfluidics, surface acoustic wave, surface plasmon resonance

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5 Improvement in the Photocatalytic Activity of Nanostructured Manganese Ferrite – Type of Materials by Mechanochemical Activation

Authors: Katerina Zaharieva, Katya Milenova, Zara Cherkezova-Zheleva, Alexander Eliyas, Boris Kunev, Ivan Mitov

Abstract:

The synthesized nanosized manganese ferrite-type of samples have been tested as photocatalysts in the reaction of oxidative degradation of model contaminant Reactive Black 5 (RB5) dye in aqueous solutions under UV irradiation. As it is known this azo dye is applied in the textile-coloring industry and it is discharged into the waterways causing pollution. The co-precipitation procedure has been used for the synthesis of manganese ferrite-type of materials: Sample 1 - Mn0.25Fe2.75O4, Sample 2 - Mn0.5Fe2.5O4 and Sample 3 - MnFe2O4 from 0.03M aqueous solutions of MnCl2•4H2O, FeCl2•4H2O and/or FeCl3•6H2O and 0.3M NaOH in appropriate amounts. The mechanochemical activation of co-precipitated ferrite-type of samples has been performed in argon (Samples 1 and 2) or in air atmosphere (Sample 3) for 2 hours at a milling speed of 500 rpm. The mechano-chemical treatment has been carried out in a high energy planetary ball mill type PM 100, Retsch, Germany. The mass ratio between balls and powder was 30:1. As a result mechanochemically activated Sample 4 - Mn0.25Fe2.75O4, Sample 5 - Mn0.5Fe2.5O4 and Sample 6 - MnFe2O4 have been obtained. The synthesized manganese ferrite-type photocatalysts have been characterized by X-ray diffraction method and Moessbauer spectroscopy. The registered X-ray diffraction patterns and Moessbauer spectra of co-precipitated ferrite-type of materials show the presence of manganese ferrite and additional akaganeite phase. The presence of manganese ferrite and small amounts of iron phases is established in the mechanochemically treated samples. The calculated average crystallite size of manganese ferrites varies within the range 7 – 13 nm. This result is confirmed by Moessbauer study. The registered spectra show superparamagnetic behavior of the prepared materials at room temperature. The photocatalytic investigations have been made using polychromatic UV-A light lamp (Sylvania BLB, 18 W) illumination with wavelength maximum at 365 nm. The intensity of light irradiation upon the manganese ferrite-type photocatalysts was 0.66 mW.cm-2. The photocatalytic reaction of oxidative degradation of RB5 dye was carried out in a semi-batch slurry photocatalytic reactor with 0.15 g of ferrite-type powder, 150 ml of 20 ppm dye aqueous solution under magnetic stirring at rate 400 rpm and continuously feeding air flow. The samples achieved adsorption-desorption equilibrium in the dark period for 30 min and then the UV-light was turned on. After regular time intervals aliquot parts from the suspension were taken out and centrifuged to separate the powder from solution. The residual concentrations of dye were established by a UV-Vis absorbance single beam spectrophotometer CamSpec M501 (UK) measuring in the wavelength region from 190 to 800 nm. The photocatalytic measurements determined that the apparent pseudo-first-order rate constants calculated by linear slopes approximating to first order kinetic equation, increase in following order: Sample 3 (1.1х10-3 min-1) < Sample 1 (2.2х10-3 min-1) < Sample 2 (3.3 х10-3 min-1) < Sample 4 (3.8х10-3 min-1) < Sample 6 (11х10-3 min-1) < Sample 5 (15.2х10-3 min-1). The mechanochemically activated manganese ferrite-type of photocatalyst samples show significantly higher degree of oxidative degradation of RB5 dye after 120 minutes of UV light illumination in comparison with co-precipitated ferrite-type samples: Sample 5 (92%) > Sample 6 (91%) > Sample 4 (63%) > Sample 2 (53%) > Sample 1 (42%) > Sample 3 (15%). Summarizing the obtained results we conclude that the mechanochemical activation leads to a significant enhancement of the degree of oxidative degradation of the RB5 dye and photocatalytic activity of tested manganese ferrite-type of catalyst samples under our experimental conditions. The mechanochemically activated Mn0.5Fe2.5O4 ferrite-type of material displays the highest photocatalytic activity (15.2х10-3 min-1) and degree of oxidative degradation of the RB5 dye (92%) compared to the other synthesized samples. Especially a significant improvement in the degree of oxidative degradation of RB5 dye (91%) has been determined for mechanochemically treated MnFe2O4 ferrite-type of sample with the highest extent of substitution of iron ions by manganese ions than in the case of the co-precipitated MnFe2O4 sample (15%). The mechanochemically activated manganese ferrite-type of samples show good photocatalytic properties in the reaction of oxidative degradation of RB5 azo dye in aqueous solutions and it could find potential application for dye removal from wastewaters originating from textile industry.

Keywords: nanostructured manganese ferrite-type materials, photocatalytic activity, Reactive Black 5, water treatment

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4 Identification of the Antimicrobial Property of Double Metal Oxide/Bioactive Glass Nanocomposite Against Multi Drug Resistant Staphylococcus aureus Causing Implant Infections

Authors: M. H. Pazandeh, M. Doudi, S. Barahimi, L. Rahimzadeh Torabi

Abstract:

The use of antibiotics is essential in reducing the occurrence of adverse effects and inhibiting the emergence of antibiotic resistance in microbial populations. The necessity for a novel methodology concerning local administration of antibiotics has arisen, with particular focus on dealing with localized infections prompted by bacterial colonization of medical devices or implant materials. Bioactive glasses (BG) are extensively employed in the field of regenerative medicine, encompassing a diverse range of materials utilized for drug delivery systems. In the present investigation, various drug carriers for imipenem and tetracycline, namely single systems BG/SnO2, BG/NiO with varying proportions of metal oxide, and nanocomposite BG/SnO2/NiO, were synthesized through the sol-gel technique. The antibacterial efficacy of the synthesized samples was assessed through the utilization of the disk diffusion method with the aim of neutralizing Staphylococcus aureus as the bacterial model. The current study involved the examination of the bioactivity of two samples, namely BG10SnO2/10NiO and BG20SnO2, which were chosen based on their heightened bacterial inactivation properties. This evaluation entailed the employment of two techniques: the measurement of the pH of simulated body fluid (SBF) solution and the analysis of the sample tablets through X-ray diffraction (XRD), scanning electron microscopy (SEM), and Fourier transform infrared (FTIR) spectroscopy. The sample tablets were submerged in SBF for varying durations of 7, 14, and 28 days. The bioactivity of the composite bioactive glass sample was assessed through characterization of alterations in its surface morphology, structure, and chemical composition. This evaluation was performed using scanning electron microscopy (SEM), Fourier-transform infrared (FTIR) spectroscopy, and X-ray diffraction spectroscopy. Subsequently, the sample was immersed in simulated liquids to simulate its behavior in biological environments. The specific body fat percentage (SBF) was assessed over a 28-day period. The confirmation of the formation of a hydroxyapatite surface layer serves as a distinct indicator of bioactivity. The infusion of antibiotics into the composite bioactive glass specimen was done separately, and then the release kinetics of tetracycline and imipenem were tested in simulated body fluid (SBF). Antimicrobial effectiveness against various bacterial strains have been proven in numerous instances using both melt and sol-gel techniques to create multiple bioactive glass compositions. An elevated concentration of calcium ions within a solution has been observed to cause an increase in the pH level. In aqueous suspensions, bioactive glass particles manifest a significant antimicrobial impact. The composite bioactive glass specimen exhibits a gradual and uninterrupted release, which is highly desirable for a drug delivery system over a span of 72 hours. The reduction in absorption, which signals the loss of a portion of the antibiotic during the loading process from the initial phosphate-buffered saline solution, indicates the successful bonding of the two antibiotics to the surfaces of the bioactive glass samples. The sample denoted as BG/10SnO2/10NiO exhibits a higher loading of particles compared to the sample designated as BG/20SnO2 in the context of bioactive glass. The enriched sample demonstrates a heightened bactericidal impact on the bacteria under investigation while concurrently preserving its antibacterial characteristics. Tailored bioactive glass that incorporates hydroxyapatite, with a regulated and efficient release of drugs targeting bacterial infections, holds promise as a potential framework for bone implant scaffolds following rigorous clinical evaluation, thereby establishing potential future biomedical uses. During the modification process, the introduction of metal oxides into bioactive glass resulted in improved antibacterial characteristics, particularly in the composite bioactive glass sample that displayed the highest level of efficiency.

Keywords: antibacterial, bioactive glasses, implant infections, multi drug resistant

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3 Municipal Solid Waste Management in Ethiopia: Systematic Review of Physical and Chemical Compositions and Generation Rate

Authors: Tsegay Kahsay Gebrekidan, Gebremariam Gebrezgabher Gebremedhin, Abraha Kahsay Weldemariam, Meaza Kidane Teferi

Abstract:

Municipal solid waste management (MSWM) in Ethiopia is a complex issue with institutional, social, political, environmental, and economic dimensions, impacting sustainable development. Effective MSWM planning necessitates understanding the generation rate and composition of waste. This systematic review synthesizes qualitative and quantitative data from various sources to aggregate current knowledge, identify gaps, and provide a comprehensive understanding of municipal solid waste management in Ethiopia. The findings reveal that the generation rate of municipal solid waste in Ethiopia is 0.38 kg/ca/day, with the waste composition being predominantly food waste, followed by ash, dust, and sand, and yard waste. Over 85% of this MSW is either reusable or recyclable, with a significant portion being organic matter (73.13% biodegradable) and 11.78% recyclable materials. Physicochemical analyses reveal that Ethiopian MSW is suitable for composting and biogas production, offering opportunities to reduce environmental pollution, and GHGs, support urban agriculture, and create job opportunities. However; challenges persist, including a lack of political will, weak municipal planning, limited community awareness, and inadequate waste management infrastructure, and only 31.8% of MSW is collected legally, leading to inefficient and harmful disposal practices. To improve MSWM, Ethiopia should focus on public awareness; increased funding, infrastructure investment, private sector partnerships, and implementing the 4 R principles (reduce, reuse, and recycle). An integrated approach involving government, industry, and civil society is essential. Further research on the physicochemical properties and strategic uses of MSW is needed to enhance management practices. Implications: The comprehensive study of municipal solid waste management (MSWM) in Ethiopia reveals the intricate interplay of institutional, social, political, environmental, and economic factors that influence the nation’s sustainable development. The findings underscore the urgent need for tailored, integrated waste management strategies that are informed by a thorough understanding of MSW generation rates, composition, and current management practices. Ethiopia’s lower per capita MSW generation compared to developed countries and the predominantly organic composition of its waste present significant opportunities for sustainable waste management practices such as composting and recycling. These practices can not only minimize the environmental impact but also support urban greening, agriculture, and renewable energy production. The high organic content, suitable physicochemical properties of MSW for composting, and potential for biogas and briquette production highlight pathways for creating employment, reducing waste, and enhancing soil fertility. Despite these opportunities, Ethiopia faces substantial challenges due to inadequate political will, weak municipal planning, limited community awareness, insufficient waste management infrastructure, and poor policy implementation. The high rate of illegal waste disposal further exacerbates environmental and health issues, emphasizing the need for a more effective and integrated MSWM approach. To address these challenges and harness the potential of MSW, Ethiopia must prioritize increasing public awareness; investing in infrastructure, fostering private sector partnerships, and implementing the principles of reduce, reuse, and recycle (3 R). Developing strategies that involve all stakeholders and turning waste into valuable resources is crucial. Government, industry, and civil society must collaborate to implement integrated MSWM systems that focus on waste reduction at the source, alternative material use, and advanced recycling technologies. Further research at both federal and regional levels is essential to optimize the physicochemical analysis and strategic use of MSW. Prompt action is required to transform waste management into a pillar of sustainable urban development, ultimately improving environmental quality and human health in Ethiopia.

Keywords: biodegradable, healthy environment, integrated solid waste management, municipal

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2 “MaxSALIVA-II” Advancing a Nano-Sized Dual-Drug Delivery System for Salivary Gland Radioprotection, Regeneration and Repair in a Head and Neck Cancer Pre-Clinical Murine Model

Authors: Ziyad S. Haidar

Abstract:

Background: Saliva plays a major role in maintaining oral, dental, and general health and well-being; where it normally bathes the oral cavity acting as a clearing agent. This becomes more apparent when the amount and quality of saliva are 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 5th most common malignancy worldwide, during which the salivary glands are included within the radiation field/zone. Clinically, patients affected by salivary gland dysfunction often opt to terminate their radiotherapy course prematurely as they become malnourished and experience a significant decrease in their QoL. Accordingly, the formulation of a radio-protection/-prevention modality and development of an alternative Rx to restore damaged salivary gland tissue is eagerly awaited and highly desirable. Objectives: Assess the pre-clinical radio-protective effect and reparative/regenerative potential of layer-by-layer self-assembled lipid-polymer-based core-shell nanocapsules designed and fine-tuned 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, 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 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: cancer, head and neck, oncology, drug development, drug delivery systems, nanotechnology, nanoncology

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1 “MaxSALIVA”: A Nano-Sized Dual-Drug Delivery System for Salivary Gland Radioprotection and Repair in Head and Neck Cancer

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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