Search results for: tissue damage

Authors: Yujie Yuan, Yiyang Fan, Hong Fan

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Objective: The RNA methylation recognition protein Aly/REF export factor (ALYREF) is considered one type of “reader” protein acting as a recognition protein of m5C, has been reported involved in several biological progresses including cancer initiation and progression. 5-methylcytosine (m5C) is a conserved and prevalent RNA modification in all species, as accumulating evidence suggests its role in the promotion of tumorigenesis. It has been claimed that ALYREF mediates nuclear export of mRNA with m5C modification and regulates biological effects of cancer cells. However, the systematical regulatory pathways of ALYREF in cancer tissues have not been clarified, yet. Methods: The expression level of ALYREF in pan-cancer and their normal tissues was compared through the data acquired from The Cancer Genome Atlas (TCGA). The University of Alabama at Birmingham Cancer data analysis Portal UALCAN was used to analyze the relationship between ALYREF and clinical pathological features. The relationship between the expression level of ALYREF and prognosis of pan-cancer, and the correlation genes of ALYREF were figured out by using Gene Expression Correlation Analysis database GEPIA. Immune related genes were obtained from TISIDB (an integrated repository portal for tumor-immune system interactions). Immune-related research was conducted by using Estimation of STromal and Immune cells in MAlignant Tumor tissues using Expression data (ESTIMATE) and TIMER. Results: Based on the data acquired from TCGA, ALYREF has an obviously higher-level expression in various types of cancers compared with relevant normal tissues excluding thyroid carcinoma and kidney chromophobe. The immunohistochemical images on The Human Protein Atlas showed that ALYREF can be detected in cytoplasm, membrane, but mainly located in nuclear. In addition, a higher expression level of ALYREF in tumor tissue generates a poor prognosis in majority of cancers. According to the above results, cancers with a higher expression level of ALYREF compared with normal tissues and a significant correlation between ALYREF and prognosis were selected for further analysis. By using TISIDB, we found that portion of ALYREF co-expression genes (such as BIRC5, H2AFZ, CCDC137, TK1, and PPM1G) with high Pearson correlation coefficient (PCC) were involved in anti-tumor immunity or affect resistance or sensitivity to T cell-mediated killing. Furthermore, based on the results acquired from GEPIA, there was significant correlation between ALYREF and PD-L1. It was exposed that there is a negative correlation between the expression level of ALYREF and ESTIMATE score. Conclusion: The present study indicated that ALYREF plays a vital and universal role in cancer initiation and progression of pan-cancer through regulating mitotic progression, DNA synthesis and metabolic process, and RNA processing. The correlation between ALYREF and PD-L1 implied ALYREF may affect the therapeutic effect of immunotherapy of tumor. More evidence revealed that ALYREF may play an important role in tumor immunomodulation. The correlation between ALYREF and immune cell infiltration level indicated that ALYREF can be a potential therapeutic target. Exploring the regulatory mechanism of ALYREF in tumor tissues may expose the reason for poor efficacy of immunotherapy and offer more directions of tumor treatment.

Keywords: ALYREF, pan-cancer, immunotherapy, PD-L1

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Authors: Louise Bernier

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Under some jurisdictions (including Canada), eligible patients can request and receive medical assistance in dying (MAiD) through lethal injections, inducing their cardiocirculatory death. Those same patients can also wish to donate their organs in the process. If they qualify as organ donors, a clinical and ethical rule called the 'dead donor rule' (DDR) requires the transplant teams to wait after cardiocirculatory death is confirmed, followed by a 'no touch' period (5 minutes in Canada) before they can proceed with organ removal. The medical procedures (lethal injections) as well as the delays associated with the DDR can damage organs (mostly thoracic organs) due to prolonged anoxia. Yet, strong scientific evidences demonstrate that operating differently and reconsidering the DDR would result in more organs of better quality available for transplant. This idea generates discomfort and resistance, but it is also worth considering, especially in a context of chronic shortage of available organs. One option that could be examined for MAiD’ patients who wish and can be organ donors would be to remove vital organs while patients are still alive (and under sedation). This would imply accepting that patient’s death would occur through organ donation instead of lethal injections required under MAiD’ legal rules. It would also mean that patients requesting MAiD and wishing to be organ donors could aspire to donate better quality organs, including their heart, an altruistic gesture that carries important symbolic value for many donors and their families. Following a patient centered approach, our hypothesis is that preventing vital organ donation from a living donor in all circumstance is neither perfectly coherent with how legal mentalities have evolved lately in the field of fundamental rights nor compatible with the clinical and ethical frameworks that shape the landscape in which those complex medical decisions unfold. Through a study of the legal, ethical, and clinical rules in place, both at the national and international levels, this analysis raises questions on the numerous inconsistencies associated with respecting the DDR with patients who have chosen to die through MAiD. We will begin with an assessment of the erosion of certain national legal frameworks that pertain to the sacred nature of the right to life which now also includes the right to choose how one wishes to die. We will then study recent innovative clinical protocols tested in different countries to help address acute organ shortage problems in creative ways. We will conclude this analysis with an ethical assessment of the situation, referring to principles such as justice, autonomy, altruism, beneficence, and non-malfeasance. This study will build a strong argument in favor of starting to allow vital organ donations from living donors in countries where MAiD is already permitted.

Keywords: altruism, autonomy, dead donor rule, medical assistance in dying, non-malfeasance, organ donation

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Authors: Bishnupriya Sahoo, Prasad K. Bhaskaran

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Tropical cyclone is one among the worst natural hazards that results in a trail of destruction causing enormous damage to life, property, and coastal infrastructures. In a global perspective, the Indian Ocean is considered as one of the cyclone prone basins in the world. Specifically, the frequency of cyclogenesis in the Bay of Bengal is higher compared to the Arabian Sea. Out of the four maritime states in the East coast of India, Odisha is highly susceptible to tropical cyclone landfall. Historical records clearly decipher the fact that the frequency of cyclones have reduced in this basin. However, in the recent decades, the intensity and size of tropical cyclones have increased. This is a matter of concern as the risk and vulnerability level of Odisha coast exposed to high wind speed and gusts during cyclone landfall have increased. In this context, there is a need to assess and evaluate the severity of coastal risk, area of exposure under risk, and associated vulnerability with a higher dimension in a multi-risk perspective. Changing climate can result in the emergence of a new hazard and vulnerability over a region with differential spatial and socio-economic impact. Hence there is a need to have coastal vulnerability projections in a changing climate scenario. With this motivation, the present study attempts to estimate the destructiveness of tropical cyclones based on Power Dissipation Index (PDI) for those cyclones that made landfall along Odisha coast that exhibits an increasing trend based on historical data. The study also covers the futuristic scenarios of integral coastal vulnerability based on the trends in PDI for the Odisha coast. This study considers 11 essential and important parameters; the cyclone intensity, storm surge, onshore inundation, mean tidal range, continental shelf slope, topo-graphic elevation onshore, rate of shoreline change, maximum wave height, relative sea level rise, rainfall distribution, and coastal geomorphology. The study signifies that over a decadal scale, the coastal vulnerability index (CVI) depends largely on the incremental change in variables such as cyclone intensity, storm surge, and associated inundation. In addition, the study also performs a critical analysis on the modulation of PDI on storm surge and inundation characteristics for the entire coastal belt of Odisha State. Interestingly, the study brings to light that a linear correlation exists between the storm-tide with PDI. The trend analysis of PDI and its projection for coastal Odisha have direct practical applications in effective coastal zone management and vulnerability assessment.

Keywords: Bay of Bengal, coastal vulnerability index, power dissipation index, tropical cyclone

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Authors: Catarina Bento, Ana Carolina Gonçalves, Fábio Jesus, Luís Rodrigues Silva

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Increasing evidence suggests that a diet rich in fruits and vegetables plays important roles in the prevention of chronic diseases, such as heart disease, cancer, stroke, diabetes, Alzheimer’s disease, among others. Fruits and vegetables gained prominence due their richness in bioactive compounds, being the focus of many studies due to their biological properties acting as health promoters. Prunus avium Linnaeus (L.), commonly known as sweet cherry has been the centre of attention due to its health benefits, and has been highly studied. In Portugal, most of the cherry production comes from the Fundão region. The Saco is one of the most important cultivar produced in this region, attributed with geographical protection. In this work, we prepared 3 extracts through solid-phase extraction (SPE): a whole extract, fraction I (non-coloured phenolics) and fraction II (coloured phenolics). The three extracts were used to determine the phenolic profile of Saco cultivar by liquid chromatography with diode array detection (LC-DAD) technique. This was followed by the evaluation of their biological potential, testing the extracts’ capacity to scavenge free-radicals (DPPH•, nitric oxide (•NO) and superoxide radical (O2●-)) and to inhibit α-glucosidase enzyme of all extracts. Additionally, we evaluated, for the first time, the protective effects against peroxyl radical (ROO•)-induced hemoglobin oxidation and hemolysis in human erythrocytes. A total of 16 non-coloured phenolics were detected, 3-O-caffeoylquinic and ρ-coumaroylquinic acids were the main ones, and 6 anthocyanins were found, among which cyanidin-3-O-rutinoside represented the majority. In respect to antioxidant activity, Saco showed great antioxidant potential in a concentration-dependent manner, demonstrated through the DPPH•,•NO and O2●-radicals, and greater ability to inhibit the α-glucosidase enzyme in comparison to the regular drug acarbose used to treat diabetes. Additionally, Saco proved to be effective to protect erythrocytes against oxidative damage in a concentration-dependent manner against hemoglobin oxidation and hemolysis. Our work demonstrated that Saco cultivar is an excellent source of phenolic compounds which are natural antioxidants that easily capture reactive species, such as ROO• before they can attack the erythrocytes’ membrane. In a general way, the whole extract showed the best efficiency, most likely due to a synergetic interaction between the different compounds. Finally, comparing the two separate fractions, the coloured fraction showed the most activity in all the assays, proving to be the biggest contributor of Saco cherries’ biological activity.

Keywords: biological potential, coloured phenolics, non-coloured phenolics, sweet cherry

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Authors: Ghada Al-Kafaji, Mohamed Sabry

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Mitochondria are the site of cellular respiration and produce energy in the form of adenosine triphosphate (ATP) via oxidative phosphorylation. They are the major source of intracellular reactive oxygen species (ROS) and are also direct target to ROS attack. Oxidative stress and ROS-mediated disruptions of mitochondrial function are major components involved in the pathogenicity of diabetic complications. In this work, the changes in mitochondrial DNA (mtDNA) copy number, biogenesis, gene expression of mtDNA-encoded subunits of electron transport chain (ETC) complexes, and mitochondrial function in response to hyperglycemia-induced ROS and the effect of direct inhibition of ROS on mitochondria were investigated in an in vitro model of diabetic nephropathy using human renal mesangial cells. The cells were exposed to normoglycemic and hyperglycemic conditions in the presence and absence of Mn(III)tetrakis(4-benzoic acid) porphyrin chloride (MnTBAP) or catalase for 1, 4 and 7 days. ROS production was assessed by the confocal microscope and flow cytometry. mtDNA copy number and PGC-1a, NRF-1, and TFAM, as well as ND2, CYTB, COI, and ATPase 6 transcripts, were all analyzed by real-time PCR. PGC-1a, NRF-1, and TFAM, as well as ND2, CYTB, COI, and ATPase 6 proteins, were analyzed by Western blotting. Mitochondrial function was determined by assessing mitochondrial membrane potential and adenosine triphosphate (ATP) levels. Hyperglycemia-induced a significant increase in the production of mitochondrial superoxide and hydrogen peroxide at day 1 (P < 0.05), and this increase remained significantly elevated at days 4 and 7 (P < 0.05). The copy number of mtDNA and expression of PGC-1a, NRF-1, and TFAM as well as ND2, CYTB, CO1 and ATPase 6 increased after one day of hyperglycemia (P < 0.05), with a significant reduction in all those parameters at 4 and 7 days (P < 0.05). The mitochondrial membrane potential decreased progressively at 1 to 7 days of hyperglycemia with the parallel progressive reduction in ATP levels over time (P < 0.05). MnTBAP and catalase treatment of cells cultured under hyperglycemic conditions attenuated ROS production reversed renal mitochondrial oxidative stress and improved mtDNA, mitochondrial biogenesis, and function. These results show that hyperglycemia-induced ROS caused an early increase in mtDNA copy number, mitochondrial biogenesis and mtDNA-encoded gene expression of the ETC subunits in human mesangial cells as a compensatory response to the decline in mitochondrial function, which precede the mtDNA defect and mitochondrial dysfunction with a progressive oxidative response. Protection from ROS-mediated damage to renal mitochondria induced by hyperglycemia may be a novel therapeutic approach for the prevention/treatment of DN.

Keywords: diabetic nephropathy, hyperglycemia, reactive oxygen species, oxidative stress, mtDNA, mitochondrial dysfunction, manganese superoxide dismutase, catalase

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Authors: Javier Enciso-Benavides, Fredy Fabian, Carlos Castaneda, Luis Alfaro, Alex Choque, Aparicio Aguilar, Javier Enciso

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Background: The use of biomarkers in breast cancer diagnosis, therapy, and prognosis has gained increasing interest. Cancer stem cells (CSCs) are a subpopulation of tumor cells that can drive tumor initiation and may cause relapse. Therefore, due to the importance of diagnosis, therapy, and prognosis, several biomarkers that characterize CSCs have been identified; however, in treatment-naïve triple-negative breast tumors, there is an urgent need to identify new biomarkers and therapeutic targets. According to this, the aim of this study was to identify serum proteins associated with cancer stem cells and pluripotency in women with triple-negative breast tumors in order to subsequently identify a biomarker for this type of breast tumor. Material and Methods: Whole blood samples from 12 women with histopathologically diagnosed triple-negative breast tumors were used after obtaining informed consent from the patient. Blood serum was obtained by conventional procedure and frozen at -80ºC. Identification of cancer stem cell-associated proteins was performed by matrix-assisted laser desorption/ionisation-assisted laser desorption/ionisation mass spectrometry (MALDI-TOF MS), protein analysis was obtained using the AB Sciex TOF/TOF™ 5800 system (AB Sciex, USA). Sequences not aligned by ProteinPilot™ software were analyzed by Protein BLAST. Results: The following proteins related to pluripotency and cancer stem cells were identified by MALDI TOF/TOF mass spectrometry: A-chain, Serpin A12 [Homo sapiens], AIEBP [Homo sapiens], Alpha-one antitrypsin, AT {internal fragment} [human, partial peptide, 20 aa] [Homo sapiens], collagen alpha 1 chain precursor variant [Homo sapiens], retinoblastoma-associated protein variant [Homo sapiens], insulin receptor, CRA_c isoform [Homo sapiens], Hydroxyisourate hydrolase [Streptomyces scopuliridis], MUCIN-6 [Macaca mulatta], Alpha-actinin-3 [Chrysochloris asiatica], Polyprotein M, CRA_d isoform, partial [Homo sapiens], Transcription factor SOX-12 [Homo sapiens]. Recommendations: The serum proteins identified in this study should be investigated in the exosome of triple-negative breast cancer stem cells and in the blood serum of women without breast cancer. Subsequently, proteins found only in the blood serum of women with triple-negative breast cancer should be identified in situ in triple-negative breast cancer tissue in order to identify a biomarker to study the evolution of this type of cancer, or that could be a therapeutic target. Conclusions: Eleven cancer stem cell-related serum proteins were identified in 12 women with triple-negative breast cancer, of which MUCIN-6, retinoblastoma-associated protein variant, transcription factor SOX-12, and collagen alpha 1 chain are the most representative and have not been studied so far in this type of breast tumor. Acknowledgement: This work was supported by Proyecto CONCYTEC–Banco Mundial “Mejoramiento y Ampliacion de los Servicios del Sistema Nacional de Ciencia Tecnología e Innovacion Tecnologica” 8682-PE (104-2018-FONDECYT-BM-IADT-AV).

Keywords: triple-negative breast cancer, MALDI TOF/TOF MS, serum proteins, cancer stem cells

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Authors: Sherif Fakher

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Hydrogen has been gaining a lot of global attention as an uprising contributor in the energy sector. Labeled as an energy carrier, hydrogen is used in many industries and can be used to generate electricity via fuel cells. Blue hydrogen involves the production of hydrogen from hydrocarbons using different processes that emit CO₂. However, the CO₂ is captured and stored. Hence, very little environmental damage occurs during the hydrogen production process. This research investigates the ability to use different catalysts for the production of hydrogen from different hydrocarbon sources, including coal, oil, and gas, using a two-step Aquathermolysis reaction. The research presents the results of experiments conducted to evaluate different catalysts and also highlights the main advantages of this process over other blue hydrogen production methods, including methane steam reforming, autothermal reforming, and oxidation. Two methods of hydrogen generation were investigated including partial oxidation and aquathermolysis. For those two reactions, the reaction kinetics, thermodynamics, and medium were all investigated. Following this, experiments were conducted to test the hydrogen generation potential from both methods. The porous media tested were sandstone, ash, and prozzolanic material. The spent oils used were spent motor oil and spent vegetable oil from cooking. Experiments were conducted at temperatures up to 250 C and pressures up to 3000 psi. Based on the experimental results, mathematical models were developed to predict the hydrogen generation potential at higher thermodynamic conditions. Since both partial oxidation and aquathermolysis require relatively high temperatures to undergo, it was important to devise a method by which these high temperatures can be generated at a low cost. This was done by investigating two factors, including the porous media used and the reliance on the spent oil. Of all the porous media used, the ash had the highest thermal conductivity. The second step was the partial combustion of part of the spent oil to generate the heat needed to reach the high temperatures. This reduced the cost of the heat generation significantly. For the partial oxidation reaction, the spent oil was burned in the presence of a limited oxygen concentration to generate carbon monoxide. The main drawback of this process was the need for burning. This resulted in the generation of other harmful and environmentally damaging gases. Aquathermolysis does not rely on burning, which makes it the cleaner alternative. However, it needs much higher temperatures to run the reaction. When comparing the hydrogen generation potential for both using gas chromatography, aquathermolysis generated 23% more hydrogen using the same volume of spent oil compared to partial oxidation. This research introduces the concept of using spent oil for hydrogen production. This can be a very promising method to produce a clean source of energy using a waste product. This can also help reduce the reliance on freshwater for hydrogen generation which can divert the usage of freshwater to other more important applications.

Keywords: blue hydrogen production, catalytic aquathermolysis, direct carbon dioxide capture, CCUS

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Authors: Nadeem Munawar, Tariq Mahmood, Paula Rivadeneira, Ali Akhter

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In this paper, we review on rodent species which are common inhabitants of agricultural landscapes where they are an important prey source for a wide variety of avian, reptilian, and mammalian predators. Agricultural fields are surrounded by fallow land, which provide suitable sites for shelter and breeding for rodents, while shrubs, grasses, annual weeds and forbs may provide supplementary food. The assemblage of rodent’s fauna in the cropland habitats including cropped fields, meadows and adjacent field structures like hedgerows, woodland and field margins fluctuates seasonally. The mature agricultural crops provides good source of food and shelter to the rodents and these factors along with favorable climatic factors/season facilitate breeding activities of these rodent species. Changes in vegetation height and vegetative cover affect two important aspects of a rodent’s life: food and shelter. In addition, during non-crop period vegetation can be important for building nests above or below ground and it provides thermal protection for rodents from heat and cold. The review revealed that rodents form a very diverse group of mammals, ranging from tiny pigmy mice to big capybaras, from arboreal flying squirrels to subterranean mole rats, from opportunistic omnivores (e.g. Norway rats) to specialist feeders (e.g. the North African fat sand rats that feed on a single family of plants only). It is therefore no surprise that some species thrive well under the conditions that are found in agricultural fields. The review on the population dynamics of the rodent species indicated that they are agricultural pests probably due to the heterogeneous landscape and to the high rotativity of vegetable crop cultivation. They also cause damage to various crops, directly and indirectly, by gnawing, spoilage, contamination and hoarding activities, besides this behavior they have also significance importance in agricultural habitat. The burrowing activities of rodents alter the soil properties around their burrows which improve its aeration, infiltration, increase the water holding capacity and thus encourage plant growth. These properties are beneficial for the soil because they affect absorption of phosphorus, absorption zinc, copper, other nutrients and the uptake of water and thus rodents are known as indicator species in agricultural fields. Our review suggests that wide crop field’s borders, particularly those contiguous to various cropland fields, should be understood as priority sites for nesting, feeding, and cover for the rodent’s fauna. The goal of this review paper is to provide a comprehensive synthesis of understanding regarding rodent habitat and biodiversity in agricultural landscapes.

Keywords: agricultural landscapes, food, indicator species, shelter

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Authors: N. Garrós, P. Bustos, N. Beirampour, R. Mohammadi, M. Mallandrich, A.C. Calpena, H. Colom

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Atopic dermatitis (AD) is a persistent skin condition characterized by chronic inflammation caused by an autoimmune response. It is a prevalent clinical issue that requires continual treatment to enhance the patient's quality of life. Systemic therapy often involves the use of glucocorticoids or immunosuppressants to manage symptoms. Our objective was to create and assess topical liposomal formulations containing Baricitinib (BNB), a reversible inhibitor of Janus-associated kinase (JAK), which is involved in various immune responses. These formulations were intended to address flare-ups and improve treatment outcomes for AD. We created three distinct liposomal formulations by combining different amounts of 1-palmitoyl-2-oleoyl-glycero-3-phosphocholine (POPC), cholesterol (CHOL), and ceramide (CER): (i) pure POPC, (ii) POPC mixed with CHOL (at a ratio of 8:2, mol/mol), and (iii) POPC mixed with CHOL and CER (at a ratio of 3.6:2.4:4.0 mol/mol/mol). We conducted various tests to determine the formulations' skin tolerance, irritancy capacity, and their ability to cause erythema and edema on altered skin. We also assessed the transepidermal water loss (TEWL) and skin hydration of rabbits to evaluate the efficacy of the formulations. Histological analysis, the HET-CAM test, and the modified Draize test were all used in the evaluation process. The histological analysis revealed that liposome POPC and POPC:CHOL avoided any damage to the tissues structures. The HET-CAM test showed no irritation effect caused by any of the three liposomes, and the modified Draize test showed a good Draize score for erythema and edema. Liposome POPC effectively counteracted the impact of xylol on the skin, and no erythema or edema was observed during the study. TEWL values were constant for all the liposomes with similar values to the negative control (within the range 8 - 15 g/h·m2, which means a healthy value for rabbits), whereas the positive control showed a significant increase. The skin hydration values were constant and followed the trend of the negative control, while the positive control showed a steady increase during the tolerance study. In conclusion, the developed formulations containing BNB exhibited no harmful or irritating effects, they did not demonstrate any irritant potential in the HET-CAM test and liposomes POPC and POPC:CHOL did not cause any structural alteration according to the histological analysis. These positive findings suggest that additional research is necessary to evaluate the efficacy of these liposomal formulations in animal models of the disease, including mutant animals. Furthermore, before proceeding to clinical trials, biochemical investigations should be conducted to better understand the mechanisms of action involved in these formulations.

Keywords: baricitinib, HET-CAM test, histological study, JAK inhibitor, liposomes, modified draize test

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Authors: Farid Khosravikia, Patricia Clayton

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The main objective of this work is to evaluate the advantages and disadvantages of various machine learning techniques in two key steps of seismic hazard and risk assessment of different types of structures. The first step is the development of ground-motion models, which are used for forecasting ground-motion intensity measures (IM) given source characteristics, source-to-site distance, and local site condition for future events. IMs such as peak ground acceleration and velocity (PGA and PGV, respectively) as well as 5% damped elastic pseudospectral accelerations at different periods (PSA), are indicators of the strength of shaking at the ground surface. Typically, linear regression-based models, with pre-defined equations and coefficients, are used in ground motion prediction. However, due to the restrictions of the linear regression methods, such models may not capture more complex nonlinear behaviors that exist in the data. Thus, this study comparatively investigates potential benefits from employing other machine learning techniques as statistical method in ground motion prediction such as Artificial Neural Network, Random Forest, and Support Vector Machine. The results indicate the algorithms satisfy some physically sound characteristics such as magnitude scaling distance dependency without requiring pre-defined equations or coefficients. Moreover, it is shown that, when sufficient data is available, all the alternative algorithms tend to provide more accurate estimates compared to the conventional linear regression-based method, and particularly, Random Forest outperforms the other algorithms. However, the conventional method is a better tool when limited data is available. Second, it is investigated how machine learning techniques could be beneficial for developing probabilistic seismic demand models (PSDMs), which provide the relationship between the structural demand responses (e.g., component deformations, accelerations, internal forces, etc.) and the ground motion IMs. In the risk framework, such models are used to develop fragility curves estimating exceeding probability of damage for pre-defined limit states, and therefore, control the reliability of the predictions in the risk assessment. In this study, machine learning algorithms like artificial neural network, random forest, and support vector machine are adopted and trained on the demand parameters to derive PSDMs for them. It is observed that such models can provide more accurate estimates of prediction in relatively shorter about of time compared to conventional methods. Moreover, they can be used for sensitivity analysis of fragility curves with respect to many modeling parameters without necessarily requiring more intense numerical response-history analysis.

Keywords: artificial neural network, machine learning, random forest, seismic risk analysis, seismic hazard analysis, support vector machine

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Authors: Prajna Paramita Naik, Sujit Kumar Bhutia

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

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

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Authors: Bastien Sanglard, Lou Magnat, Ligia Barna, Julian Carrey, Sébastien Lachaize

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Cooking is a primary need for humans, several techniques being used around the globe based on different sources of energy: electricity, solid fuel (wood, coal...), fuel or liquefied petroleum gas. However, all of them leads to direct or indirect greenhouse gas emissions and sometimes health damage in household. Therefore, the solar concentrated power represent a great option to lower the damages because of a cleaner using phase. Nevertheless, the construction phase of the solar cooker still requires primary energy and materials, which leads to environmental impacts. The aims of this work is to analyse the ecological impacts of a commercialaluminium parabola and to compare it with other means of cooking, taking the boiling of 2 litres of water three times a day during 40 years as the functional unit. Life cycle assessment was performed using the software Umberto and the EcoInvent database. Calculations were realized over more than 13 criteria using two methods: the international panel on climate change method and the ReCiPe method. For the reflector itself, different aluminium provenances were compared, as well as the use of recycled aluminium. For the structure, aluminium was compared to iron (primary and recycled) and wood. Results show that climate impacts of the studied parabola was 0.0353 kgCO2eq/kWh when built with Chinese aluminium and can be reduced by 4 using aluminium from Canada. Assessment also showed that using 32% of recycled aluminium would reduce the impact by 1.33 and 1.43 compared to the use of primary Canadian aluminium and primary Chinese aluminium, respectively. The exclusive use of recycled aluminium lower the impact by 17. Besides, the use of iron (recycled or primary) or wood for the structure supporting the reflector significantly lowers the impact. The impact categories of the ReCiPe method show that the parabola made from Chinese aluminium has the heaviest impact - except for metal resource depletion - compared to aluminium from Canada, recycled aluminium or iron. Impact of solar cooking was then compared to gas stove and induction. The gas stove model was a cast iron tripod that supports the cooking pot, and the induction plate was as well a single spot plate. Results show the parabolic solar cooker has the lowest ecological impact over the 13 criteria of the ReCiPe method and over the global warming potential compared to the two other technologies. The climate impact of gas cooking is 0.628kgCO2/kWh when used with natural gas and 0.723 kgCO2/kWh when used with a bottle of gas. In each case, the main part of emissions came from gas burning. Induction cooking has a global warming potential of 0.12 kgCO2eq/kWh with the electricity mix of France, 96.3% of the impact being due to electricity production. Therefore, the electricity mix is a key factor for this impact: for instance, with the electricity mix of Germany and Poland, impacts are 0.81kgCO2eq/kWh and 1.39 kgCO2eq/kWh, respectively. Therefore, the parabolic solar cooker has a real ecological advantages compared to both gas stove and induction plate.

Keywords: life cycle assessement, solar concentration, cooking, sustainability

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Authors: Nnadi Ezekiel Oluwaseun Ejiofor

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This research investigates the effects of poor cost estimation, material cost variations, and payment punctuality on the financial health and execution of construction projects in Nigeria. To achieve the objectives of the study, a quantitative research approach was employed, and data was gathered through an online survey of 74 construction industry professionals consisting of quantity surveyors, contractors, and other professionals. The study surveyed input on cost estimation errors, price fluctuations, and payment delays, among other factors. The responses of the respondents were analyzed using a five-point Likert scale and the Relative Importance Index (RII). The findings demonstrated that the errors in cost estimating in the Bill of Quantity (BOQ) have a high degree of negative impact on the reputation and image of the participants in the projects. The greatest effect was experienced on the likelihood of obtaining future endeavors for contractors (mean value = 3.42), followed by the likelihood of obtaining new commissions by quantity surveyors (mean value = 3.40). The level of inaccuracy in costing that undershoots exposes them to risks was most serious in terms of easement of construction and effects of shortage of funds to pursue bankruptcy (hence fears of mean value = 3.78). There was also considerable financial damage as a result of cost underestimation, whereby contractors suffered the worst loss in profit (mean value = 3.88). Every expense comes with its own peculiar risk and uncertainty. Pressure on the cost of materials and every other expense attributed to the building and completion of a structure adds risks to the performance figures of a project. The greatest weight (mean importance score = 4.92) was attributed to issues like market inflation in building materials, while the second greatest weight (mean importance score = 4.76) was due to increased transportation charges. On the other hand, delays in payments arising from issues of the clients like poor availability of funds (RII=0.71) and contracting issues such as disagreements on the valuation of works done (RII=0.72) or other reasons were also found to lead to project delays and additional costs. The results affirm the importance of proper cost estimation on the health of organization finances and project risks and finishes within set time limits. As for the suggestions, it is proposed to progress on the methods of costing, engender better communications with the stakeholders, and manage the delays by way of contracting and financial control. This study enhances the existing literature on construction project management by suggesting ways to deal with adverse cost inaccuracies and availability of materials due to delays in payments which, if addressed, would greatly improve the economic performance of the construction business.

Keywords: cost estimation, construction project management, material price fluctuations, payment delays, financial impact

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Authors: N. Szczepanska, B. Kudlak, G. Yotova, S. Tsakovski, J. Namiesnik

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In the scientific literature related to the widely understood issue of packaging materials designed to have contact with food (food contact materials), there is much information on raw materials used for their production, as well as their physiochemical properties, types, and parameters. However, not much attention is given to the issues concerning migration of toxic substances from packaging and its actual influence on the health of the final consumer, even though health protection and food safety are the priority tasks. The goal of this study was to estimate the impact of particular foodstuff packaging type, food production, and storage conditions on the degree of leaching of potentially toxic compounds and endocrine disruptors to foodstuffs using the acute toxicity test Microtox and XenoScreen YES YAS assay. The selected foodstuff packaging materials were metal cans used for fish storage and tetrapak. Five stimulants respectful to specific kinds of food were chosen in order to assess global migration: distilled water for aqueous foods with a pH above 4.5; acetic acid at 3% in distilled water for acidic aqueous food with pH below 4.5; ethanol at 5% for any food that may contain alcohol; dimethyl sulfoxide (DMSO) and artificial saliva were used in regard to the possibility of using it as an simulation medium. For each packaging three independent variables (temperature and contact time) factorial design simulant was performed. Xenobiotics migration from epoxy resins was studied at three different temperatures (25°C, 65°C, and 121°C) and extraction time of 12h, 48h and 2 weeks. Such experimental design leads to 9 experiments for each food simulant as conditions for each experiment are obtained by combination of temperature and contact time levels. Each experiment was run in triplicate for acute toxicity and in duplicate for estrogen disruption potential determination. Multi-factor analysis of variation (MANOVA) was used to evaluate the effects of the three main factors solvent, temperature (temperature regime for cup), contact time and their interactions on the respected dependent variable (acute toxicity or estrogen disruption potential). From all stimulants studied the most toxic were can and tetrapak lining acetic acid extracts that are indication for significant migration of toxic compounds. This migration increased with increase of contact time and temperature and justified the hypothesis that food products with low pH values cause significant damage internal resin filling. Can lining extracts of all simulation medias excluding distilled water and artificial saliva proved to contain androgen agonists even at 25°C and extraction time of 12h. For tetrapak extracts significant endocrine potential for acetic acid, DMSO and saliva were detected.

Keywords: food packaging, extraction, migration, toxicity, biotest

Procedia PDF Downloads 181

Authors: Uchenna Nkiruka Umeononihu, Adenike Kuku, Oludele Odekanyin, Olubunmi Babalola, Femi Agboola, Rapheal Okonji

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In this study, a lectin from the bulb of Dioscorea bulbifera was purified, characterised, and its acute and sub-acute toxicity was investigated with a view to evaluate its toxic effects in mice. The protein from the bulb was extracted by homogenising 50 g of the bulb in 500 ml of phosphate buffered saline (0.025 M) of pH 7.2, stirred for 3 hr, and centrifuged at the speed of 3000 rpm. Blood group and sugar specificity assays of the crude extract were determined. The lectin was purified in a two-step procedure- gel filtration on Sephadex G-75 and affinity chromatography on Sepharose 4-B arabinose. The degree of purity of the purified lectin was ascertained by SDS-polyacrylamide gel electrophoresis. Detection of covalently bound carbohydrate was carried out with Periodic Acid-Schiffs (PAS) reagent staining technique. Effects of temperature, pH, and EDTA on the lectin were carried out using standard methods. This was followed by acute toxicity studies via oral and subcutaneous routes using mice. The animals were monitored for mortality and signs of toxicity. The sub-acute toxicity studies were carried out using rats. Different concentrations of the lectin were administered twice daily for 5 days via the subcutaneous route. The animals were sacrificed on the sixth day; blood samples and liver tissues were collected. Biochemical assays (determination of total protein, direct bilirubin, Alanine aminotransferase (ALT), Aspartate aminotransferase (AST), catalase (CAT), and superoxide dismutase (SOD)) were carried out on the serum and liver homogenates. The collected organs (heart, liver, kidney, and spleen) were subjected to histopathological analysis. The results showed that lectin from the bulbs of Dioscorea bulbifera agglutinated non-specifically the erythrocytes of the human ABO system as well as rabbit erythrocytes. The haemagglutinating activity was strongly inhibited by arabinose and dulcitol with minimum inhibitory concentrations of 0.781 and 6.25, respectively. The lectin was purified to homogeneity with native and subunit molecular weights of 56,273 and 29,373 Daltons, respectively. The lectin was thermostable up to 30 0C and lost 25 %, 33.3 %, and 100 % of its heamagglutinating activity at 40°C, 50°C, and 60°C, respectively. The lectin was maximally active at pH 4 and 5 but lost its total activity at pH eight, while EDTA (10 mM) had no effect on its haemagglutinating activity. PAS reagent staining showed that the lectin was not a glycoprotein. The sub-acute studies on rats showed elevated levels of ALT, AST, serum bilirubin, total protein in serum and liver homogenates suggesting damage to liver and spleen. The study concluded that the aerial bulb of D. bulbifera lectin was non-specific in its heamagglutinating activity and dimeric in its structure. The lectin shared some physicochemical characteristics with lectins from other Dioscorecea species and was moderately toxic to the liver and spleen of treated animals.

Keywords: Dioscorea bulbifera, heamagglutinin, lectin, toxicity

Procedia PDF Downloads 127

Authors: Christian Lauter, Corin Reuter, Shuang Wu, Thomas Troester

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Lightweight construction became more and more important over the last decades in several applications, e.g. in the automotive or aircraft sector. This is the result of economic and ecological constraints on the one hand and increasing safety and comfort requirements on the other hand. In the field of lightweight design, different approaches are used due to specific requirements towards the technical systems. The use of endless carbon fiber reinforced plastics (CFRP) offers the largest weight saving potential of sometimes more than 50% compared to conventional metal-constructions. However, there are very limited industrial applications because of the cost-intensive manufacturing of the fibers and production technologies. Other disadvantages of pure CFRP-structures affect the quality control or the damage resistance. One approach to meet these challenges is hybrid materials. This means CFRP and sheet metal are combined on a material level. Therefore, new opportunities for innovative process routes are realizable. Hybrid lightweight design results in lower costs due to an optimized material utilization and the possibility to integrate the structures in already existing production processes of automobile manufacturers. In recent and current research, the advantages of two-layered hybrid materials have been pointed out, i.e. the possibility to realize structures with tailored mechanical properties or to divide the curing cycle of the epoxy resin into two steps. Current research work at the Chair for Automotive Lightweight Design (LiA) at the Paderborn University focusses on production processes for fiber-metal-laminates. The aim of this work is the development and qualification of a large-scale production process for high-performance fiber-metal-laminates (FML) for industrial applications in the automotive or aircraft sector. Therefore, the prepreg-press-technology is used, in which pre-impregnated carbon fibers and sheet metals are formed and cured in a closed, heated mold. The investigations focus e.g. on the realization of short process chains and cycle times, on the reduction of time-consuming manual process steps, and the reduction of material costs. This paper gives an overview over the considerable steps of the production process in the beginning. Afterwards experimental results are discussed. This part concentrates on the influence of different process parameters on the mechanical properties, the laminate quality and the identification of process limits. Concluding the advantages of this technology compared to conventional FML-production-processes and other lightweight design approaches are carried out.

Keywords: composite material, fiber-metal-laminate, lightweight construction, prepreg-press-technology, large-series production

Procedia PDF Downloads 240

Authors: Khelladi Hadj Mostefa, Krouf Djamil, Taleb-Dida Nawel

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Background: Obesity results from a prolonged imbalance between energy intake and energy expenditure, as depending on basal metabolic rate. Oils and proteins from sea have important therapeutic (such as obesity and hypercholesterolemia) and antioxidant effects. Sardine are a widely consumed fish in the Mediterranean region. Its consumption provides humans with various nutrients such as oils (rich in omega 3 plyunsaturated fatty acids)) and proteins. Methods: Sardine oil (SO) and sardine proteins (SP) were extracted and purified. Mixture of vegetable oils (olive-walnut-sunflower) were prepared from oils produced in Algeria. Eighteen wistar rats are fed a high fat diet enriched with 1% cholesterol for 30 days to induce obesity and hypercholesterolemia. The rats are divided into 3 groups. The first group consumes 20% sardine protein combined with 5% sardine oil (38% SFA (saturated fatty acids), 31% MIFA (monounsaturated fatty acids) and 31% PIFA (polyunsaturated fatty acids)) (SPso). The second group consumes 20% sardine protein combined with 5% of a mixture of vegetable oils (VO) containing 13% SFA, 58% MIFA and 29% PIFA (PSvo), and the third group consuming 20% casein combined with 5% of the mixture of vegetable oils and serves as a semi-synthetic reference (CASvo). Body weights and glycaemia are measured weekly After 28 days of experimentation, the rats are sacrificed, the blood and the liver removed. Serum assays of total cholesterol (TC) and triglycerides (TG) were performed by enzymatic colorimetric methods. Evaluation of lipid peroxidation was performed by assaying thiobarbituric acid reactive species (TBARS) and hydroperoxides values. The protein oxidation was performed by assaying carbonyl derivatives values. Finally, evaluation of antioxidant defense is made by measuring the activity of antioxidant enzymes, the superoxide dismutase (SOD) and the catalase (CAT).Results: After 28 days, the body weight (BW) of the rats increased significantly in SPso and SPvo groups compared to CAS group, by +11% and 7%, respectively. Cholesterolemia (TC) increased significantly in the SPso and SPvo groups compared to the CAS group (P<0.01), while triglyceridemia (TG) decreased significantly in the SPso group compared to SPvo and CAS groups (P<0.01). Albumin (marker of inflammation) increased in the PSs group compared to SPvo and CAS groups by +35% and +13%, respectively. The serum TBARS levels are -40% lower in SPso group compared to SPvo group, and they are -80% and -76% lower in SPso compared to SPvo and CAS groups, respectively. The level of carbonyls derivatives in the serum and liver are significantly reduced in the SPso group compared to the SPvo and CAS groups. Superoxide dismutase (SOD) activity decreased in liver of SPso group compared to SPvo group (P<0.01). While that of CAT is increased in liver tissue of SPso group compared to SPvo group (P<0.01). Conclusion: Sardine oil combined with sardine protein has a hypotriglyceridemic effect, reduces body weight, attenuates inflammation and seems to protect against lipid peroxidation and protein oxidation and increases antioxidant defense in hypercholesterolemic and obese rats. This could be in favor of a protective effect against obesity and cardiovascular diseases.

Keywords: rat, obesity, hypercholesterolemia, sardine protein, sardine oil, vegetable oils mixture, lipid peroxidation, protein oxidation, antioxidant defense

Procedia PDF Downloads 66

Authors: Babak Forouraghi

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

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

Procedia PDF Downloads 59

Authors: Alessandra Pardu, Elena Curti, Marco Caredda, Alessio Dedola, Margherita Addis, Massimo Pes, Antonio Pirisi, Tonina Roggio, Sergio Uzzau, Roberto Anedda

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Some of the artisanal cheeses products of European Countries certificated as PDO (Protected Designation of Origin) are made from raw milk. To recognise potential frauds (e.g. pasteurisation or thermisation of milk aimed at raw milk cheese production), the alkaline phosphatase (ALP) assay is currently applied only for pasteurisation, although it is known to have notable limitations for the validation of ALP enzymatic state in nonbovine milk. It is known that frauds considerably impact on customers and certificating institutions, sometimes resulting in a damage of the product image and potential economic losses for cheesemaking producers. Robust, validated, and univocal analytical methods are therefore needed to allow Food Control and Security Organisms, to recognise a potential fraud. In an attempt to develop a new reliable method to overcome this issue, Time-Domain Nuclear Magnetic Resonance (TD-NMR) spectroscopy has been applied in the described work. Daily fresh milk was analysed raw (680.00 µL in each 10-mm NMR glass tube) at least in triplicate. Thermally treated samples were also produced, by putting each NMR tube of fresh raw milk in water pre-heated at temperatures from 68°C up to 72°C and for up to 3 min, with continuous agitation, and quench-cooled to 25°C in a water and ice solution. Raw and thermally treated samples were analysed in terms of 1H T2 transverse relaxation times with a CPMG sequence (Recycle Delay: 6 s, interpulse spacing: 0.05 ms, 8000 data points) and quasi-continuous distributions of T2 relaxation times were obtained by CONTIN analysis. In line with previous data collected by high field NMR techniques, a decrease in the spin-spin relaxation constant T2 of the predominant 1H population was detected in heat-treated milk as compared to raw milk. The decrease of T2 parameter is consistent with changes in chemical exchange and diffusive phenomena, likely associated to changes in milk protein (i.e. whey proteins and casein) arrangement promoted by heat treatment. Furthermore, experimental data suggest that molecular alterations are strictly dependent on the specific heat treatment conditions (temperature/time). Such molecular variations in milk, which are likely transferred to cheese during cheesemaking, highlight the possibility to extend the TD-NMR technique directly on cheese to develop a method for assessing a fraud related to the use of a milk thermal treatment in PDO raw milk cheese. Results suggest that TDNMR assays might pave a new way to the detailed characterisation of heat treatments of milk.

Keywords: cheese fraud, milk, pasteurisation, TD-NMR

Procedia PDF Downloads 242

Authors: M. P. S. Tomar, Neelam Bansal

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Histomorphological, histochemical and scanning electron microscopic observations were recorded in developing cornea of buffalo fetuses. The samples from fetal cornea were collected in appropriate fixative from slaughter house and Veterinary Clinics, GADVASU, Ludhiana. The microscopic slides were stained for detailed histomorphological and histochemical studies. The scanning electron microscopic studies were performed at Electron microscopy & Nanobiology Lab, PAU Ludhiana. In present study, it was observed that, in 36 days (d) fetus, the corneal epithelium was well marked single layered structure which was placed on stroma mesenchyme. Cornea appeared as the continuation of developing sclera. The thickness of cornea and its epithelium increased as well as the epithelium started becoming double layered in 47d fetus at corneo-scleral junction. The corneal thickness in this stage suddenly increased thus easily distinguished from developing sclera. The separation of corneal endothelium from stroma was evident as a single layered epithelium. The stroma possessed numerous fibroblasts in 49d stage eye. Descemet’s membrane was appeared at 52d stage. The limbus area was separated by a depression from the developing cornea in 61d stage. In 65d stage, the Bowman’s layer was more developed. Fibroblasts were arranged parallel to each other as well as parallel to the surface of developing cornea in superficial layers. These fibroblasts and fibers were arranged in wavy pattern in the center of stroma. Corneal epithelium started to be stratified as a double layered epithelium was present in this age of fetal eye. In group II (>120 Days), the corneal epithelium was stratified towards a well marked irido-corneal angle. The stromal fibroblasts followed a complete parallel arrangement in its entire thickness. In full term fetuses, a well developed cornea was observed. It was a fibrous layer which had five distinct layers. From outside to inwards were described as the outer most layer was the 7-8 layered corneal epithelial, subepithelial basement membrane (Bowman’s membrane), substantia propria or stroma, posterior limiting membrane (Descemet’s membrane) and the posterior epithelium (corneal endothelium). The corneal thickness and connective tissue elements were continued to be increased. It was 121.39 + 3.73µ at 36d stage which increased to 518.47 + 4.98 µ in group III fetuses. In fetal life, the basement membrane of corneal epithelium and endothelium depicted strong to intense periodic Acid Schiff’s (PAS) reaction. At the irido-corneal angle, the endothelium of blood vessels was also positive for PAS activity. However, cornea was found mild positive for alcian blue reaction. The developing cornea showed strong reaction for basic proteins in outer epithelium and the inner endothelium layers. Under low magnification scanning electron microscope, cornea showed two types of cells viz. light cells and dark cells. The light cells were smaller in size and had less number of microvilli in their surface than in the dark cells. Despite these surface differences between light and dark cells, the corneal surface showed the same general pattern of microvilli studding all exposed surfaces out to the cell margin. which were long (with variable height), slight tortuous slender and possessed a micro villus shaft with a very prominent knob.

Keywords: buffalo, cornea, eye, fetus, ontogeny, scanning electron microscopy

Procedia PDF Downloads 150

Authors: Apurva Singh, S. P. Jaiswar, Apala Priyadarshini, Akancha Pandey

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Objective: The aim of this study is to find the association of PON1 gene polymorphism with pesticides In RPL subjects. Background: Recurrent pregnancy loss (RPL) is defined as three or more sequential abortions before the 20th week of gestation. Pesticides and its derivatives (organochlorine and organophosphate) are proposed to accommodate a ruler chemical for RPL in the sub-humid region of India. The paraoxonase-1 enzyme (PON1) plays an important role in the toxicity of some organophosphate pesticides, with low PON1 activity being associated with higher pesticide sensitivity Methodology: This is a case-control study done in Department of Obstetrics & Gynaecology & Department of Biochemistry, K.G.M.U, Lucknow, India. The subjects were enrolled after fulfilling the inclusion & exclusion criteria. Inclusion criteria: Cases- Subject having two or more spontaneous abortions & Control- Healthy female having one or more alive child was selected. Exclusion criteria: Cases & Control- Subject having the following disease will be excluded from the study Diabetes mellitus, Hypertension, Tuberculosis, Immunocompromised patients, any endocrine disorder and genital, colon or breast cancer any other malignancies. Blood samples were collected in EDTA tubes from cases & healthy control women & genomic DNA was extracted by phenol-chloroform method. The estimation of pesticides residue from blood was done by HPLC. Biochemical estimation was also performed. Genotyping of PON1 gene polymorphism was performed by RFLP. Statistical analysis of the data was performed using the SPSS16.3 software. Results: A sum of total 14 pesticides (12 organochlorine and 2 organophosphate) selected on the basis of their persistent nature and consumption rate. The significant level of pesticide (ppb) estimated by the Mann whiney test and it was found to be significant at higher level of β-HCH (p:0.04), γ-HCH (p:0.001), δ-HCH (p: 0.002), chloropyrifos (p:0.001), pp-DDD (p:0.001) and fenvalrate (p: 0.001) in case group compare to its control. The level of antioxidant enzymes were found to be significantly decreased among the cases. Wild homozygous TT was more frequent and prevalent among control groups. However, heterozygous group (Tt) was more in cases than control groups (CI-0.3-1.3) (p=0.06). Conclusion: Higher levels of pesticides with endocrine disrupting potential in cases indicate the possible role of these compounds as one of the causes of recurrent pregnancy loss. Possibly, increased pesticide level appears to indicate increased levels of oxidative damage that has been associated with the possible cause of Recurrent Miscarriage, it may reflect indirect evidence of toxicity rather than the direct cause. Since both factors are reported to increase risk, individuals with higher levels of these 'Toxic compounds' especially in 'high-risk genotypes' might be more susceptible to recurrent pregnancy loss.

Keywords: paraoxonase, pesticides, PON1, RPL

Procedia PDF Downloads 143

Authors: Rijnbout-St.James Willem, Lindner Volkhard, Scholand Mary Beth, Ashton M. Tillett, Di Gennaro Michael Jude, Smith Silvia Enrica

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Introduction: Fibrosing lung diseases are characterized by changes in the lung interstitium and are classified based on etiology: 1) environmental/exposure-related, 2) autoimmune-related, 3) sarcoidosis, 4) interstitial pneumonia, and 4) idiopathic. Among interstitial lung diseases (ILD) idiopathic forms, idiopathic pulmonary fibrosis (IPF) is the most severe. Pathogenesis of IPF is characterized by an increased presence of proinflammatory mediators, resulting in alveolar injury, where injury to alveolar epithelium precipitates an increase in collagen deposition, subsequently thickening the alveolar septum and decreasing gas exchange. Identifying biomarkers implicated in the pathogenesis of lung fibrosis is key to developing new therapies and improving the efficacy of existing therapies. The transforming growth factor-beta (TGF-B1), a mediator of tissue repair associated with WNT5A signaling, is partially responsible for fibroblast proliferation in ILD and is the target of Pirfenidone, one of the antifibrotic therapies used for patients with IPF. Canonical TGF-B signaling is mediated by the proteins SMAD 2/3, which are, in turn, indirectly regulated by Collagen Triple Helix Repeat Containing 1 (CTHRC1). In this study, we tested the following hypotheses: 1) CTHRC1 is more elevated in the ILD cohort compared to unaffected controls, and 2) CTHRC1 is differently expressed among ILD types. Material and Methods: CTHRC1 levels were measured by ELISA in 171 plasma samples from the deidentified University of Utah ILD cohort. Data represent a cohort of 131 ILD-affected participants and 40 unaffected controls. CTHRC1 samples were categorized by a pulmonologist based on affectation status and disease subtypes: IPF (n = 45), sarcoidosis (4), nonspecific interstitial pneumonia (16), hypersensitivity pneumonitis (n = 7), interstitial pneumonia (n=13), autoimmune (n = 15), other ILD - a category that includes undifferentiated ILD diagnoses (n = 31), and unaffected controls (n = 40). We conducted a single-factor ANOVA of plasma CTHRC1 levels to test whether CTHRC1 variance among affected and non-affected participants is statistically significantly different. In-silico analysis was performed with Ingenuity Pathway Analysis® to characterize the role of CTHRC1 in the pathway of lung fibrosis. Results: Statistical analyses of CTHRC1 in plasma samples indicate that the average CTHRC1 level is significantly higher in ILD-affected participants than controls, with the autoimmune ILD being higher than other ILD types, thus supporting our hypotheses. In-silico analyses show that CTHRC1 indirectly activates and phosphorylates SMAD3, which in turn cross-regulates TGF-B1. CTHRC1 also may regulate the expression and transcription of TGFB-1 via WNT5A and its regulatory relationship with CTNNB1. Conclusion: In-silico pathway analyses demonstrate that CTHRC1 may be an important biomarker in ILD. Analysis of plasma samples indicates that CTHRC1 expression is positively associated with ILD affectation, with autoimmune ILD having the highest average CTHRC1 values. While characterizing CTHRC1 levels in plasma can help to differentiate among ILD types and predict response to Pirfenidone, the extent to which plasma CTHRC1 level is a function of ILD severity or chronicity is unknown.

Keywords: interstitial lung disease, CTHRC1, idiopathic pulmonary fibrosis, pathway analyses

Procedia PDF Downloads 191

Authors: Tim Bolle, Franziska Kreimendahl, Thomas Gries, Stefan Jockenhoevel

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The therapeutic treatment of extensive, deep wounds is limited. Autologous split-skin grafts are used as a so-called ‘gold standard’. Most common deficits are the defects at the donor site, the risk of scarring as well as the limited availability and quality of the autologous grafts. The aim of this project is a tissue engineered dermal-epidermal skin replacement to overcome the limitations of the gold standard. A key requirement for the development of such a three-dimensional implant is the formation of a functional capillary-like network inside the implant to ensure a sufficient nutrient and gas supply. Tailored three-dimensional warp knitted spacer fabrics are used to reinforce the mechanically week fibrin gel-based scaffold and further to create a directed in vitro pre-vascularization along the parallel-oriented pile yarns within a co-culture. In this study various three-dimensional warp knitted spacer fabrics were developed in a factorial design to analyze the influence of the machine parameters such as the stitch density and the pattern of the fabric on the scaffold performance and further to determine suitable parameters for a successful fibrin gel-incorporation and a physiological performance of the scaffold. The fabrics were manufactured on a Karl Mayer double-bar raschel machine DR 16 EEC/EAC. A fine machine gauge of E30 was used to ensure a high pile yarn density for sufficient nutrient, gas and waste exchange. In order to ensure a high mechanical stability of the graft, the fabrics were made of biocompatible PVDF yarns. Key parameters such as the pore size, porosity and stress/strain behavior were investigated under standardized, controlled climate conditions. The influence of the input parameters on the mechanical and morphological properties as well as the ability of fibrin gel incorporation into the spacer fabric was analyzed. Subsequently, the pile yarns of the spacer fabrics were colonized with Human Umbilical Vein Endothelial Cells (HUVEC) to analyze the ability of the fabric to further function as a guiding structure for a directed vascularization. The cells were stained with DAPI and investigated using fluorescence microscopy. The analysis revealed that the stitch density and the binding pattern have a strong influence on both the mechanical and morphological properties of the fabric. As expected, the incorporation of the fibrin gel was significantly improved with higher pore sizes and porosities, whereas the mechanical strength decreases. Furthermore, the colonization trials revealed a high cell distribution and density on the pile yarns of the spacer fabrics. For a tailored reinforcing structure, the minimum porosity and pore size needs to be evaluated which still ensures a complete incorporation of the reinforcing structure into the fibrin gel matrix. That will enable a mechanically stable dermal graft with a dense vascular network for a sufficient nutrient and oxygen supply of the cells. The results are promising for subsequent research in the field of reinforcing mechanically weak biological scaffolds and develop functional three-dimensional scaffolds with an oriented pre-vascularization.

Keywords: fibrin-gel, skin replacement, spacer fabric, pre-vascularization

Procedia PDF Downloads 257

Authors: Davide Cocchi, Andrea Zucchelli, Luca Raimondi, Maria Brugo Tommaso

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The increasing attention is given to the issues of environmental pollution and climate change is exponentially stimulating the development of electrically propelled vehicles powered by renewable energy, in particular, the solar one. Given the small amount of solar energy that can be stored and subsequently transformed into propulsive energy, it is necessary to develop vehicles with high mechanical, electrical and aerodynamic efficiencies along with reduced masses. The reduction of the masses is of fundamental relevance especially for the unsprung masses, that is the assembly of those elements that do not undergo a variation of their distance from the ground (wheel, suspension system, hub, upright, braking system). Therefore, the reduction of unsprung masses is fundamental in decreasing the rolling inertia and improving the drivability, comfort, and performance of the vehicle. This principle applies even more in solar propelled vehicles, equipped with an electric motor that is connected directly to the wheel hub. In this solution, the electric motor is integrated inside the wheel. Since the electric motor is part of the unsprung masses, the development of compact and lightweight solutions is of fundamental importance. The purpose of this research is the design development and optimization of a CFRP 16 wheel hub motor for solar propulsion vehicles that can carry up to four people. In addition to trying to maximize aspects of primary importance such as mass, strength, and stiffness, other innovative constructive aspects were explored. One of the main objectives has been to achieve a high geometric packing in order to ensure a reduced lateral dimension, without reducing the power exerted by the electric motor. In the final solution, it was possible to realize a wheel hub motor assembly completely comprised inside the rim width, for a total lateral overall dimension of less than 100 mm. This result was achieved by developing an innovative connection system between the wheel and the rotor with a double purpose: centering and transmission of the driving torque. This solution with appropriate interlocking noses allows the transfer of high torques and at the same time guarantees both the centering and the necessary stiffness of the transmission system. Moreover, to avoid delamination in critical areas, evaluated by means of FEM analysis using 3D Hashin damage criteria, electrospun nanofibrous mats have been interleaved between CFRP critical layers. In order to reduce rolling resistance, the rim has been designed to withstand high inflation pressure. Laboratory tests have been performed on the rim using the Digital Image Correlation technique (DIC). The wheel has been tested for fatigue bending according to E/ECE/324 R124e.

Keywords: composite laminate, delamination, DIC, lightweight vehicle, motor hub wheel, nanofiber

Procedia PDF Downloads 214

Authors: Mohamed Bualhamam

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Due to the complex nature of tourism resources of the Northern part of the United Arab Emirates (UAE), the potential of Geographical Information Systems (GIS) and Remote Sensing (RS) in resolving these issues was used. The study was an attempt to use existing GIS data layers to identify sensitive natural environment and archaeological heritage resources that may be threatened by increased urban growth and give some specific recommendations to protect the area. By identifying sensitive natural environment and archaeological heritage resources, public agencies and citizens are in a better position to successfully protect important natural lands and direct growth away from environmentally sensitive areas. The paper concludes that applications of GIS and RS in study of urban growth impact in tourism resources are a strong and effective tool that can aid in tourism planning and decision-making. The study area is one of the fastest growing regions in the country. The increase in population along the region, as well as rapid growth of towns, has increased the threat to natural resources and archeological sites. Satellite remote sensing data have been proven useful in assessing the natural resources and in monitoring the changes. The study used GIS and RS to identify sensitive natural environment and archaeological heritage resources that may be threatened by increased urban growth. The result of GIS analyses shows that the Northern part of the UAE has variety for tourism resources, which can use for future tourism development. Rapid urban development in the form of small towns and different economic activities are showing in different places in the study area. The urban development extended out of old towns and have negative affected of sensitive tourism resources in some areas. Tourism resources for the Northern part of the UAE is a highly complex resources, and thus requires tools that aid in effective decision making to come to terms with the competing economic, social, and environmental demands of sustainable development. The UAE government should prepare a tourism databases and a GIS system, so that planners can be accessed for archaeological heritage information as part of development planning processes. Applications of GIS in urban planning, tourism and recreation planning illustrate that GIS is a strong and effective tool that can aid in tourism planning and decision- making. The power of GIS lies not only in the ability to visualize spatial relationships, but also beyond the space to a holistic view of the world with its many interconnected components and complex relationships. The worst of the damage could have been avoided by recognizing suitable limits and adhering to some simple environmental guidelines and standards will successfully develop tourism in sustainable manner. By identifying sensitive natural environment and archaeological heritage resources of the Northern part of the UAE, public agencies and private citizens are in a better position to successfully protect important natural lands and direct growth away from environmentally sensitive areas.

Keywords: GIS, natural environment, UAE, urban growth

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Authors: Maryam Mohammad Hadi, Heather Nesbitt, Hamzah Masood, Hashim Ahmed, Mark Emberton, John Callan, Alexander MacRobert, Anthony McHale, Nikolitsa Nomikou

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Sonodynamic therapy (SDT) utilises ultrasound in combination with sensitizers, such as porphyrins, for the production of cytotoxic reactive oxygen species (ROS) and the confined ablation of tumours. Ultrasound can be applied locally, and the acoustic waves, at frequencies between 0.5-2 MHz, are transmitted efficiently through tissue. SDT does not require highly toxic agents, and the cytotoxic effect only occurs upon ultrasound exposure at the site of the lesion. Therefore, this approach is not associated with adverse side effects. Further highlighting the benefits of SDT, no cancer cell population has shown resistance to therapy-triggered ROS production or their cytotoxic effects. This is particularly important, given the as yet unresolved issues of radiation and chemo-resistance, to the authors’ best knowledge. Another potential future benefit of this approach – considering its non-thermal mechanism of action – is its possible role as an adjuvant to immunotherapy. Substantial pre-clinical studies have demonstrated the efficacy and targeting capability of this therapeutic approach. However, SDT has yet to be fully characterised and appropriately exploited for the treatment of cancer. In this study, a formulation based on multistimulus-responsive sensitizer-containing nanoparticles that can accumulate in advanced prostate tumours and increase the therapeutic efficacy of SDT has been developed. The formulation is based on a polyglutamate-tyrosine (PGATyr) co-polymer carrying hematoporphyrin. The efficacy of SDT in this study was demonstrated using prostate cancer as the translational exemplar. The formulation was designed to respond to the microenvironment of advanced prostate tumours, such as the overexpression of the proteolytic enzymes, cathepsin-B and prostate-specific membrane antigen (PSMA), that can degrade the nanoparticles, reduce their size, improving both diffusions throughout the tumour mass and cellular uptake. The therapeutic modality was initially tested in vitro using LNCaP and PC3 cells as target cell lines. The SDT efficacy was also examined in vivo, using male SCID mice bearing LNCaP subcutaneous tumours. We have demonstrated that the PGATyr co-polymer is digested by cathepsin B and that digestion of the formulation by cathepsin-B, at tumour-mimicking conditions (acidic pH), leads to decreased nanoparticle size and subsequent increased cellular uptake. Sonodynamic treatment, at both normoxic and hypoxic conditions, demonstrated ultrasound-induced cytotoxic effects only for the nanoparticle-treated prostate cancer cells, while the toxicity of the formulation in the absence of ultrasound was minimal. Our in vivo studies in immunodeficient mice, using the hematoporphyrin-containing PGATyr nanoparticles for SDT, showed a 50% decrease in LNCaP tumour volumes within 24h, following IV administration of a single dose. No adverse effects were recorded, and body weight was stable. The results described in this study clearly demonstrate the promise of SDT to revolutionize cancer treatment. It emphasizes the potential of this therapeutic modality as a fist line treatment or in combination treatment for the elimination or downstaging of difficult to treat cancers, such as prostate, pancreatic, and advanced colorectal cancer.

Keywords: sonodynamic therapy, nanoparticles, tumour ablation, ultrasound

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Authors: K. H. Reeta, Bhavana Prasher, Mitali Mukerji, Dhwani Dholakia, Sangeeta Khanna, Archana Vats, Shivam Pandey, Sandeep Seth, Subir Kumar Maulik

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Introduction Research has demonstrated a connection between coronary artery disease (CAD) and genetics. We did a deep literature mining using both bioinformatics and manual efforts to identify the susceptible polymorphisms in coronary artery disease. Further, the study sought to validate these findings in an Asian population. Methodology In first phase, we used an automated pipeline which organizes and presents structured information on SNPs, Population and Diseases. The information was obtained by applying Natural Language Processing (NLP) techniques to approximately 28 million PubMed abstracts. To accomplish this, we utilized Python scripts to extract and curate disease-related data, filter out false positives, and categorize them into 24 hierarchical groups using named Entity Recognition (NER) algorithms. From the extensive research conducted, a total of 466 unique PubMed Identifiers (PMIDs) and 694 Single Nucleotide Polymorphisms (SNPs) related to coronary artery disease (CAD) were identified. To refine the selection process, a thorough manual examination of all the studies was carried out. Specifically, SNPs that demonstrated susceptibility to CAD and exhibited a positive Odds Ratio (OR) were selected, and a final pool of 324 SNPs was compiled. The next phase involved validating the identified SNPs in DNA samples of 96 CAD patients and 37 healthy controls from Indian population using Global Screening Array. ResultsThe results exhibited out of 324, only 108 SNPs were expressed, further 4 SNPs showed significant difference of minor allele frequency in cases and controls. These were rs187238 of IL-18 gene, rs731236 of VDR gene, rs11556218 of IL16 gene and rs5882 of CETP gene. Prior researches have reported association of these SNPs with various pathways like endothelial damage, susceptibility of vitamin D receptor (VDR) polymorphisms, and reduction of HDL-cholesterol levels, ultimately leading to the development of CAD. Among these, only rs731236 had been studied in Indian population and that too in diabetes and vitamin D deficiency. For the first time, these SNPs were reported to be associated with CAD in Indian population. Conclusion: This pool of 324 SNP s is a unique kind of resource that can help to uncover risk associations in CAD. Here, we validated in Indian population. Further, validation in different populations may offer valuable insights and contribute to the development of a screening tool and may help in enabling the implementation of primary prevention strategies targeted at the vulnerable population.

Keywords: coronary artery disease, single nucleotide polymorphism, susceptible SNP, bioinformatics

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Authors: Anselm Ego Onyimonyi, Maduako Johnpaul O.

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The study was designed to investigate into the socio-ecological impact of migration of Fulani herders in Anambra state of Nigeria, through a climate justice lens. Nigeria is one of the world’s most densely populated countries with a population of over 284 million people, half of which are considered to be in abject poverty. There is no doubt that livestock production provides sustainable contributions to food security and poverty reduction to Nigeria economy, but not without some environmental implications like any other economic activities. Nigeria is recognized as being vulnerable to climate change. Climate change and global warming if left unchecked will cause adverse effects on livelihoods in Nigeria, such as livestock production, crop production, fisheries, forestry and post-harvest activities, because the rainfall regimes and patterns will be altered, floods which devastate farmlands would occur, increase in temperature and humidity which increases pest and disease would occur and other natural disasters like desertification, drought, floods, ocean and storm surges, which not only damage Nigerians’ livelihood but also cause harm to life and property, would occur. This and other climatic issue as it affects Fulani herdsmen was what this study investigated. In carrying out this research, a survey research design was adopted. A simple sampling technique was used. One local government area (LGA) was selected purposively from each of the four agricultural zone in the state based on its predominance of Fulani herders. For appropriate sampling, 25 respondents from each of the four Agricultural zones in the state were randomly selected making up the 100 respondent being sampled. Primary data were generated by using a set of structured 5-likert scale questionnaire. Data generated were analyzed using SPSS and the result presented using descriptive statistics. From the data analyzed, the study indentified; Unpredicted rainfall (mean = 3.56), Forest fire (mean = 4.63), Drying Water Source (mean = 3.99), Dwindling Grazing (mean 4.43), Desertification (mean = 4.44), Fertile land scarcity (mean = 3.42) as major factor predisposing Fulani herders to migrate southward while rejecting Natural inclination to migrate (mean = 2.38) and migration to cause trouble as a factor. On the reason why Fulani herders are trying to establish a permanent camp in Anambra state; Moderate temperature (mean= 3.60), Avoiding overgrazing (4.42), Search for fodder and water (mean = 4.81) and (mean = 4.70) respectively, Need for market (4.28), Favorable environment (mean = 3.99) and Access to fertile land (3.96) were identified. It was concluded that changing climatic variables necessitated the migration of herders from Northern Nigeria to areas in the South were the variables are most favorable to the herders and their animals.

Keywords: socio-ecological, migration, fulani, climate, justice, lens

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Authors: Maria Angela Bedini, Fabio Bronzini

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The Italian experiences, positive and negative, of the post-earthquake are conditioned by long times and structural bureaucratic constraints, also motivated by the attempt to contain mafia infiltration and corruption. The transition from the operational phase of the emergency to the planning phase of the reconstruction project is thus hampered by a series of inefficiencies and delays, incompatible with the need for rapid recovery of the territories in crisis. In fact, intervening in areas affected by seismic events means at the same time associating the reconstruction plan with an urban and territorial rehabilitation project based on strategies and tools in which prevention and safety play a leading role in the regeneration of territories in crisis and the return of the population. On the contrary, the earthquakes that took place in Italy have instead further deprived the territories affected of the minimum requirements for habitability, in terms of accessibility and services, accentuating the depopulation process, already underway before the earthquake. The objective of this work is to address with implementing and programmatic tools the procedures and strategies to be put in place, today and in the future, in Italy and abroad, to face the challenge of the reconstruction of activities, sociality, services, risk mitigation: a protocol of operational intentions and firm points, open to a continuous updating and implementation. The methodology followed is that of the comparison in a synthetic form between the different Italian experiences of the post-earthquake, based on facts and not on intentions, to highlight elements of excellence or, on the contrary, damage. The main results obtained can be summarized in technical comparison cards on good and bad practices. With this comparison, we intend to make a concrete contribution to the reconstruction process, certainly not only related to the reconstruction of buildings but privileging the primary social and economic needs. In this context, the recent instrument applied in Italy of the strategic urban and territorial SUM (Minimal Urban Structure) and the strategic monitoring process become dynamic tools for supporting reconstruction. The conclusions establish, by points, a protocol of interventions, the priorities for integrated socio-economic strategies, multisectoral and multicultural, and highlight the innovative aspects of 'inversion' of priorities in the reconstruction process, favoring the take-off of 'accelerator' interventions social and economic and a more updated system of coexistence with risks. In this perspective, reconstruction as a necessary response to the calamitous event can and must become a unique opportunity to raise the level of protection from risks and rehabilitation and development of the most fragile places in Italy and abroad.

Keywords: an operational protocol for reconstruction, operational priorities for coexistence with seismic risk, social and economic interventions accelerators of building reconstruction, the difficult post-earthquake reconstruction in Italy

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Authors: Katarzyna Bialik-Wąs, Klaudia Pluta, Dagmara Malina, Małgorzata Miastkowska

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In recent years, biocompatible hydrogels have been used more and more in medical applications, especially as modern dressings and drug delivery systems. The main goal of this research was the characteristics of bio-hybrid hydrogel materials incorporated with the nanocarrier-drug system, which enable the release in a gradual and prolonged manner, up to 7 days. Therefore, the use of such a combination will provide protection against mechanical damage and adequate hydration. The proposed bio-hybrid hydrogels are characterized by: transparency, biocompatibility, good mechanical strength, and the dual release system, which allows for gradual delivery of the active substance, even up to 7 days. Bio-hybrid hydrogels based on sodium alginate (SA), poly(vinyl alcohol) (PVA), glycerine, and Aloe vera solution (AV) were obtained through the chemical crosslinking method using poly(ethylene glycol) diacrylate as a crosslinking agent. Additionally, a nanocarrier-drug system was incorporated into SA/PVA/AV hydrogel matrix. Here, studies were focused on the release profiles of active substances from bio-hybrid hydrogels using the USP4 method (DZF II Flow-Through System, Erweka GmbH, Langen, Germany). The equipment incorporated seven in-line flow-through diffusion cells. The membrane was placed over support with an orifice of 1,5 cm in diameter (diffusional area, 1.766 cm²). All the cells were placed in a cell warmer connected with the Erweka heater DH 2000i and the Erweka piston pump HKP 720. The piston pump transports the receptor fluid via seven channels to the flow-through cells and automatically adapts the setting of the flow rate. All volumes were measured by gravimetric methods by filling the chambers with Milli-Q water and assuming a density of 1 g/ml. All the determinations were made in triplicate for each cell. The release study of the model active substance was carried out using a regenerated cellulose membrane Spectra/Por®Dialysis Membrane MWCO 6-8,000 Carl Roth® Company. These tests were conducted in buffer solutions – PBS at pH 7.4. A flow rate of receptor fluid of about 4 ml /1 min was selected. The experiments were carried out for 7 days at a temperature of 37°C. The released concentration of the model drug in the receptor solution was analyzed using UV-Vis spectroscopy (Perkin Elmer Company). Additionally, the following properties of the modified materials were studied: physicochemical, structural (FT-IR analysis), morphological (SEM analysis). Finally, the cytotoxicity tests using in vitro method were conducted. The obtained results exhibited that the dual release system allows for the gradual and prolonged delivery of the active substances, even up to 7 days.

Keywords: wound dressings, SA/PVA hydrogels, nanocarrier-drug system, USP4 method

Procedia PDF Downloads 147