Search results for: lymphocyte cell line

Authors: Taha Kadir Yesin, Hanyu Liu, Zhangfan Ding, Amit Singh, Qi Tian, Yuheng Zhang, Biswajyoti Borah, Junyu Chen, Anjali P. Kusumbe

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The skeletal structure and bone marrow endothelium collectively form a critical functional unit essential for bone development, health, and aging. At the core of osteogenesis and bone formation lies the dynamic process of angiogenesis. In this study, we reveal a potent endogenous anabolic NCAM1-14.3.3. ζδ-derived- Peptide interaction, which stimulates bone angiogenesis and osteogenesis during homeostasis, aging, and age-related bone diseases. Employing high-resolution imaging and inducible cell-specific mouse genetics, our results elucidate the pivotal role of the NCAM1-14.3.3.ζδ-derived-Peptide interaction in driving the expansion of Clec14a+ angiogenic endothelial cells. Notably, Clec14a+ endothelial cells express key osteogenic factors. The NCAM1-14.3.3.ζδ-derived-Peptide interaction in osteoblasts drives osteoblast differentiation, ultimately contributing to the genesis of bone. Moreover, the NCAM1-14.3.3.ζδ-derived-Peptide interaction leads to a reduction in bone resorption. In age-associated vascular and bone loss diseases, stimulating the NCAM1-14.3.3.ζδ-derived-Peptide interaction not only promotes angiogenesis but also reverses bone loss. Consequently, harnessing the endogenous anabolic potential of the NCAM1-14.3.3.ζδ-derived-Peptide interaction emerges as a promising therapeutic modality for managing age-related bone diseases.

Keywords: endothelial cell, NCAM1, Clec14a, 14.3.3.ζδ

Procedia PDF Downloads 63

Authors: Emanuela Chiarella, Clelia Nisticò, Nicola Lombardo, Giovanna Lucia Piazzetta, Nadia Lobello, Maria Mesuraca

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Killian’s Antrochoanal Polyp is a benign lesion of the maxillary sinus characterized by unilateral nasal obstruction, pus discharge, and headache. It affects, more commonly children and young adults. Although its etiology still remains unclear, chronic inflammation, autoreactivity, allergies, and viral infections are strongly associated with its formation and development, resulting in nasal tissue remodeling. We aimed to investigate the stem cells components which reside in this pathological tissue. In particular, we adopted a protocol for the isolation and culturing of mesenchymal stem cells from surgical biopsies of three Killian nasal polyp patients (KNP-MSCs) as well as from their healthy nasal tissue (HNT-MSCs) that were used as controls. The immunophenotype profile of HNT-MSCs and KNP-MSCs was more similar, with a marked positivity for CD73, CD90, and CD105 expression, while being negative for CD34 and CD14 haematopoietic genes. Cell proliferation assay showed that KNP-MSCs had a replicative disadvantage compared to HNT-MSCs, as evidenced by the significantly lower number of cells in the S-phase of the cell cycle. KNP-MSCs also took longer to close a wound than HNT-MSCs, indicating a partial epithelial phenotype in which low levels of ICAM-1 mRNA and a significant increase in E-CAD transcript were detectable. Subsequently, the differentiation potential of both MSCs populations was analyzed by inducing osteoblastic or adipocyte differentiation for up to 20 days. KNP-MSCs showed the ability to differentiate into osteoblasts, although ALP activity as well as the number and size of calcium deposits were lower than osteogenic induced-HNT-MSCs. Also, mRNA levels of osteoblastic marker genes (OCN, OPN, OSX, RUNX2) resulted lower compared to control cell population. Instead, the analysis of the adipogenic differentiation potential showed a similar behavior between KNP-MSCs and HNT-MSCs considering that the amount of lipid droplets, the expression of adipocyte-specific genes (FABP4, AdipoQ, PPARγ2, LPL) and the content of triacylglycerols were almost overlapping. Taken together, these results first demonstrated that Killian's nasal polyp is a source of mesenchymal stem cells with self-renewal and multi-differentiative capabilities.

Keywords: Mesenchymal stem cells, adipogenic differentiation, osteogenic differentiation, EMT

Procedia PDF Downloads 77

Authors: Shwu-Ling Peng, Chiung-Man Tsai, Chia-Jui Weng

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Chronic micro-inflammation is a hallmark of many aging-related neurodegenerative and metabolic syndrome-driven diseases. In high glucose (HG) environment, reactive oxygen species (ROS) is generated and the ROS induced inflammation, cytokines secretion, DNA damage, and cell cycle arrest to lead to cellular senescence. Water chestnut shell (WCS) is a plant hull which containing polyphenolic compounds and showed antioxidant and anticancer activities. Orchid, which containing a natural polysaccharide compound, possesses many physiological activities including anti-inflammatory and neuroprotective effects. These agricultural plants might be able to reduce oxidative stress and inflammation. This study was used HG-induced human normal dermal fibroblasts (HG-HNDFs) as an in vitro model to disclose the effects of water extract of Phalaenopsis orchid flower (WEPF) and ethanol extract of water chestnut shell (EEWCS) on the anti-aging and their underlying molecular mechanisms. The toxicity of extracts on human normal dermal fibroblasts (HNDFs) was determined by MTT method. The senescence of cells was assayed by β-galactosidase (SA-β-gal) kit. ROS and nitrate production was analyzed by Intracellular ROS contents and ELISA, respectively. Western blotting was used to detect the proteins in cells. The results showed that the exposure of HNDFs to HG (30 mM) for 72 h were caused cellular senescence and arrested cells at G0/G1 phase. Indeed, the treatment of HG-HNDFs with WEPF (200 μg/ml) and EEWCS (10 μg/ml) significantly released cell cycle arrest and promoted cell proliferation. The G1/S phase transition regulatory proteins such as protein retinoblastoma (pRb), p53, and p16ᴵᴺᴷ⁴ᵃ depressed by WEPF and EEWCS were also observed. Additionally, the treatment of WEPF and EEWCS increased the activity of HO-1 through upregulating Nrf2 as well as decreased the ROS and NO of HG-HNDFs. Therefore, the senescence marker protein-30 (SMP30) in cells was diminished. In conclusion, the WEPF and EEWCS might inhibit HG-induced aging of HNDFs by reducing oxidative stress and free radicals.

Keywords: agricultural plant extract, anti-aging, high glucose, Phalaenopsis orchid flower, water chestnut shell

Procedia PDF Downloads 154

Authors: Zeynep Busra Velioglu, Deniz Pulat, Beril Demirbakan, Burak Ozcan, Ece Bayrak, Cevat Erisken

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Bone tissue has the ability to perform a wide array of functions including providing posture, load-bearing capacity, protection for the internal organs, initiating hematopoiesis, and maintaining the homeostasis of key electrolytes via calcium/phosphate ion storage. The most common cause for bone defects is extensive trauma and subsequent infection. Bone tissue has the self-healing capability without a scar tissue formation for the majority of the injuries. However, some may result with delayed union or fracture non-union. Such cases include reconstruction of large bone defects or cases of compromised regenerative process as a result of avascular necrosis and osteoporosis. Several surgical methods exist to treat bone defects, including Ilizarov method, Masquelete technique, growth factor stimulation, and bone replacement. Unfortunately, these are technically demanding and come with noteworthy disadvantages such as lengthy treatment duration, adverse effects on the patient’s psychology, repeated surgical procedures, and often long hospitalization times. These limitations associated with surgical techniques make bone substitutes an attractive alternative. Here, it was hypothesized that a 3D printed scaffold will mimic trabecular bone in terms of biomechanical properties and that such scaffolds will support cell attachment and survival. To test this hypothesis, this study aimed at fabricating poly(lactic acid), PLA, structures using 3D printing technology for trabecular bone defects, characterizing the scaffolds and comparing with bovine trabecular bone. Capacity of scaffolds on human bone marrow stem cell (hBMSC) attachment and survival was also evaluated. Cubes with a volume of 1 cm³ having pore sizes of 0.50, 1.00 and 1.25 mm were printed. The scaffolds/grafts were characterized in terms of porosity, contact angle, compressive mechanical properties as well cell response. Porosities of the 3D printed scaffolds were calculated based on apparent densities. For contact angles, 50 µl distilled water was dropped over the surface of scaffolds, and contact angles were measured using ‘Image J’ software. Mechanical characterization under compression was performed on scaffolds and native trabecular bone (bovine, 15 months) specimens using a universal testing machine at a rate of 0.5mm/min. hBMSCs were seeded onto the 3D printed scaffolds. After 3 days of incubation with fully supplemented Dulbecco’s modified Eagle’s medium, the cells were fixed using 2% formaldehyde and glutaraldehyde mixture. The specimens were then imaged under scanning electron microscopy. Cell proliferation was determined by using EZQuant dsDNA Quantitation kit. Fluorescence was measured using microplate reader Spectramax M2 at the excitation and emission wavelengths of 485nm and 535nm, respectively. Findings suggested that porosity of scaffolds with pore dimensions of 0.5mm, 1.0mm and 1.25mm were not affected by pore size, while contact angle and compressive modulus decreased with increasing pore size. Biomechanical characterization of trabecular bone yielded higher modulus values as compared to scaffolds with all pore sizes studied. Cells attached and survived in all surfaces, demonstrating higher proliferation on scaffolds with 1.25mm pores as compared with those of 1mm. Collectively, given lower mechanical properties of scaffolds as compared to native bone, and biocompatibility of the scaffolds, the 3D printed PLA scaffolds of this study appear as candidate substitutes for bone repair and regeneration.

Keywords: 3D printing, biomechanics, bone repair, stem cell

Procedia PDF Downloads 172

Authors: Silvia Arrate, Waldo Salud, Eloy París

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The wear of cutting tools is one of the most decisive elements when planning tunneling works, programming the maintenance stops and saving the optimum stock of spare parts during the evolution of the excavation. Being able to predict the behavior of cutting tools can give a very competitive advantage in terms of costs and excavation performance, optimized to the needs of the TBM itself. The incredible evolution of data science in recent years gives the option to implement it at the time of analyzing the key and most critical parameters related to machinery with the purpose of knowing how the cutting head is performing in front of the excavated ground. Taking this as a case study, Metro Line 3 of Guadalajara in Mexico will develop the feasibility of using Specific Energy versus data science applied over parameters of Torque, Penetration, and Contact Force, among others, to predict the behavior and status of cutting tools. The results obtained through both techniques are analyzed and verified in the function of the wear and the field situations observed in the excavation in order to determine its effectiveness regarding its predictive capacity. In conclusion, the possibilities and improvements offered by the application of digital tools and the programming of calculation algorithms for the analysis of wear of cutting head elements compared to purely empirical methods allow early detection of possible damage to cutting tools, which is reflected in optimization of excavation performance and a significant improvement in costs and deadlines.

Keywords: cutting tools, data science, prediction, TBM, wear

Procedia PDF Downloads 49

Authors: Serdal Pamuk, Irem Cay

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Our model is based on the theory of reinforced random walks coupled with Michealis-Menten mechanisms which view endothelial cell receptors as the catalysts for transforming both tumor and macrophage derived tumor angiogenesis factor (TAF) into proteolytic enzyme which in turn degrade the basal lamina. The model consists of two main parts. First part has seven differential equations (DE’s) in one space dimension over the capillary, whereas the second part has the same number of DE’s in two space dimensions in the extra cellular matrix (ECM). We connect these two parts via some boundary conditions to move the cells into the ECM in order to initiate capillary formation. But, when does this movement begin? To address this question we estimate the thresholds that activate the transport equations in the capillary. We do this by using steady-state analysis of TAF equation under some assumptions. Once these equations are activated endothelial, pericyte and macrophage cells begin to move into the ECM for the initiation of angiogenesis. We do believe that our results play an important role for the mechanisms of cell migration which are crucial for tumor angiogenesis. Furthermore, we estimate the long time tendency of these three cells, and find that they tend to the transition probability functions as time evolves. We provide our numerical solutions which are in good agreement with our theoretical results.

Keywords: angiogenesis, capillary formation, mathematical analysis, steady-state, transition probability function

Procedia PDF Downloads 156

Authors: Ji Jiazheng, Wang Jingrao, Jin Xin, Zhang Hong

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Diabetes mellitus is a metabolic disease characterized by high blood sugar. A long-standing hyperglycemic state can lead to various tissue damage. Diabetic retinopathy is the most common and widely studied ocular complication and has become the leading cause of blindness in my country. At the same time, diabetes has profound clinically relevant effects on the cornea, leading to keratopathy and vision-threatening. The cornea is an avascular tissue and is sensitive to hyperglycemia, Keratopathy caused by diabetes is usually chronic, they are called diabetic keratopathy or diabetic neurotrophic keratopathy, leading to several diabetic corneal complications including delayed epithelial wound healing, recurrent erosions, neuropathy, loss of sensitivity. Corneal stem cell dysfunction in diabetic patients as an important influencing factor of diabetic keratopathy. The consequences of this condition are often underestimated. The limbus is located between the cornea and the sclera tissue. The limbal stroma consists of a series of radial elevations with fibrovascular centers known as palisades of Vogt (POV). Previous studies have shown that palisades of Vogt (POV), as the main site of limbal stem cells, plays an important role in the homeostasis of the corneal epithelium. Therefore, POV plays a vital role in the healing of corneal epithelial surgery and postoperative evaluation. IVCM can observe the condition of the corneal epithelium at the cellular level. It has profound significance and guidance for the evaluation of limbal and limbal stem cells. We have previously observed structural changes in POV in HSK and HZO patients on IVCM. At present, there have been reports involving limbal stem cell dysfunction in diabetic patients, but the specific pathogenesis is still unclear. However, there are no studies on POV morphological changes in patients with DM. Therefore, we performed statistics and compared the correlation between POV morphological changes and corneal epithelial basal cell density, corneal nerves, and length of disease in DM patients and normal humans using IVCM studies. At the same time, fundoscopy was used to observe the correlation between the thickness of RNFL and the thickness of GCC and POV in diabetic patients. And to observe the correlation between SVD, DVD and POV for research.

Keywords: confocal microscopy, fundus, limbal stem cells, diabetes

Procedia PDF Downloads 83

Authors: Elvin P. Chizenga, Heidi Abrahamse

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Cancer cell resistance to therapy is the main cause of treatment failures and the poor prognosis of cancer convalescence. The progression of cervical cancer to other parts of the genitourinary system and the reported recurrence rates are overwhelming. Current treatments, including surgery, chemo and radiation have been inefficient in eradicating the tumor cells. These treatments are also associated with poor prognosis and reduced quality of life, including fertility loss. This has inspired the need for the development of new treatment modalities to eradicate cervical cancer successfully. Photodynamic Therapy (PDT) is a modern treatment modality that induces cell death by photochemical interactions of light and a photosensitizer, which in the presence of molecular oxygen, yields a set of chemical reactions that generate Reactive Oxygen Species (ROS) and other free radical species causing cell damage. Enhancing PDT using modified drug delivery can increase the concentration of the photosensitizer in the tumor cells, and this has the potential to maximize its therapeutic efficacy. In cervical cancer, all infected cells constitutively express genes of the E6 and E7 HPV viral oncoproteins, resulting in high concentrations of E6 and E7 in the cytoplasm. This provides an opportunity for active targeting of cervical cancer cells using immune-mediated drug delivery to maximize therapeutic efficacy. The use of nanoparticles in PDT has also proven effective in enhancing therapeutic efficacy. Gold nanoparticles (AuNps) in particular, are explored for their use in biomedicine due to their biocompatibility, low toxicity, and enhancement of drug uptake by tumor cells. In this present study, a biomolecule comprising of AuNPs, anti-E6 monoclonal antibodies, and Aluminium Phthalocyanine photosensitizer was synthesized for use in targeted PDT of cervical cancer. The AuNp-Anti-E6-Sulfonated Aluminium Phthalocyanine mix (AlPcSmix) photosensitizing biomolecule was synthesized by coupling AuNps and anti-E6 monoclonal antibodies to the AlPcSmix via Polyethylene Glycol (PEG) chemical links. The final product was characterized using Transmission Electron Microscope (TEM), Zeta Potential, Uv-Vis Spectrophotometry, Fourier Transform Infrared Spectroscopy (FTIR), and X-ray diffraction (XRD), to confirm its chemical structure and functionality. To observe its therapeutic role in treating cervical cancer, cervical cancer cells, HeLa cells were seeded in 3.4 cm² diameter culture dishes at a concentration of 5x10⁵ cells/ml, in vitro. The cells were treated with varying concentrations of the photosensitizing biomolecule and irradiated using a 673.2 nm wavelength of laser light. Post irradiation cellular responses were performed to observe changes in morphology, viability, proliferation, cytotoxicity, and cell death pathways induced. Dose-Dependent response of the cells to treatment was demonstrated as significant morphologic changes, increased cytotoxicity, and decreased cell viability and proliferation This study presented a synthetic biomolecule for targeted PDT of cervical cancer. The study suggested that PDT using this AuNp- Anti-E6- AlPcSmix photosensitizing biomolecule is a very effective treatment method for the eradication of cervical cancer cells, in vitro. Further studies in vivo need to be conducted to support the use of this biomolecule in treating cervical cancer in clinical settings.

Keywords: anti-E6 monoclonal antibody, cervical cancer, gold nanoparticles, photodynamic therapy

Procedia PDF Downloads 125

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

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

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

Procedia PDF Downloads 417

Authors: N. Slepickova Kasalkova, P. Slepicka, L. Bacakova, V. Svorcik

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Tissue engineering includes combination of materials and techniques used for the improvement, repair or replacement of the tissue. Scaffolds, permanent or temporally material, are used as support for the creation of the "new cell structures". For this important component (scaffold), a variety of materials can be used. The advantage of some polymeric materials is their cytocompatibility and possibility of biodegradation. Poly(L-lactic acid) (PLLA) is a biodegradable,  semi-crystalline thermoplastic polymer. PLLA can be fully degraded into H₂O and CO₂. In this experiment, the effect of the surface modification of biodegradable polymer (performed by plasma treatment) on the various cell types was studied. The surface parameters and changes of the physicochemical properties of modified PLLA substrates were studied by different methods. Surface wettability was determined by goniometry, surface morphology and roughness study were performed with atomic force microscopy and chemical composition was determined using photoelectron spectroscopy. The physicochemical properties were studied in relation to cytocompatibility of human osteoblast (MG 63 cells), rat vascular smooth muscle cells (VSMC), and human stem cells (ASC) of the adipose tissue in vitro. A fluorescence microscopy was chosen to study and compare cell-material interaction. Important parameters of the cytocompatibility like adhesion, proliferation, viability, shape, spreading of the cells were evaluated. It was found that the modification leads to the change of the surface wettability depending on the time of modification. Short time of exposition (10-120 s) can reduce the wettability of the aged samples, exposition longer than 150 s causes to increase of contact angle of the aged PLLA. The surface morphology is significantly influenced by duration of modification, too. The plasma treatment involves the formation of the crystallites, whose number increases with increasing time of modification. On the basis of physicochemical properties evaluation, the cells were cultivated on the selected samples. Cell-material interactions are strongly affected by material chemical structure and surface morphology. It was proved that the plasma treatment of PLLA has a positive effect on the adhesion, spreading, homogeneity of distribution and viability of all cultivated cells. This effect was even more apparent for the VSMCs and ASCs which homogeneously covered almost the whole surface of the substrate after 7 days of cultivation. The viability of these cells was high (more than 98% for VSMCs, 89-96% for ASCs). This experiment is one part of the basic research, which aims to easily create scaffolds for tissue engineering with subsequent use of stem cells and their subsequent "reorientation" towards the bone cells or smooth muscle cells.

Keywords: poly(L-lactic acid), plasma treatment, surface characterization, cytocompatibility, human osteoblast, rat vascular smooth muscle cells, human stem cells

Procedia PDF Downloads 228

Authors: Yufan Mu

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High salinity process water (HSPW) is often applied in copper ore flotation to alleviate freshwater shortage; however, it is detrimental to copper flotation as it strongly enhances copper activation of pyrite. In this study, the depression effect of a strong oxidiser, potassium ferrate (𝐾₂𝐹₄), on the flotation of copper-activated pyrite was tested to realise the selective separation of pyrite from copper minerals (e.g., chalcopyrite) in flotation using HSPW. The flotation results show that when (𝐾₂𝐹₄) was added in the flotation cell during conditioning, (𝐾₂𝐹₄) could selectively depress copper-activated pyrite while improving chalcopyrite flotation. The depression mechanism of (𝐾₂𝐹₄) on pyrite was ascribed to the significant increase in the pulp potential (Eₕ), dissolved oxygen (DO) concentration and the amount of ferric oxyhydroxides as a result of ferrate decomposition. In the flotation cell, the high Eh and DO concentration promoted the oxidation of low valency metal species (𝐶⁺𝐹e²⁺) released from mineral surfaces and forged steel grinding media, and the resultant high valency metal oxyhydroxides 𝐶u(𝑂H)₂⁄Fe(OH)₃ together with the ferric oxyhydroxides from ferrate decomposition preferentially precipitated on pyrite surface due to its more cathodic nature compared with chalcopyrite, which increased pyrite surface hydrophilicity and reduced its floatability. This study reveals that (𝐾₂𝐹₄) is a highly efficient depressant for pyrite when separating copper minerals from pyrite in flotation using HSPW if dosed properly.

Keywords: copper flotation, pyrite depression, copper-activated pyrite, potassium ferrate, high salinity process water

Procedia PDF Downloads 72

Authors: Shujun Xie, Shirong Zhang, Shenglin Ma

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Background: Chronic inflammation might lead to many malignancies, and inadequate resolution could play a crucial role in tumor invasion, progression, and metastases. A randomised, double-blind, placebo-controlled trial shows that IL-1β inhibition with canakinumab could reduce incident lung cancer and lung cancer mortality in patients with atherosclerosis. The process and secretion of proinflammatory cytokine IL-1β are controlled by the inflammasome. Here we showed the correlation of the innate immune system and afatinib, a tyrosine kinase inhibitor targeting epidermal growth factor receptor (EGFR) in non-small cell lung cancer. Methods: Murine Bone marrow derived macrophages (BMDMs), peritoneal macrophages (PMs) and THP-1 were used to check the effect of afatinib on the activation of NLRP3 inflammasome. The assembly of NLRP3 inflammasome was check by co-immunoprecipitation of NLRP3 and apoptosis-associated speck-like protein containing CARD (ASC), disuccinimidyl suberate (DSS)-cross link of ASC. Lipopolysaccharide (LPS)-induced sepsis and Alum-induced peritonitis were conducted to confirm that afatinib could inhibit the activation of NLRP3 in vivo. Peripheral blood mononuclear cells (PBMCs) from non-small cell lung cancer (NSCLC) patients before or after taking afatinib were used to check that afatinib inhibits inflammation in NSCLC therapy. Results: Our data showed that afatinib could inhibit the secretion of IL-1β in a dose-dependent manner in macrophage. Moreover, afatinib could inhibit the maturation of IL-1β and caspase-1 without affecting the precursors of IL-1β and caspase-1. Next, we found that afatinib could block the assembly of NLRP3 inflammasome and the ASC speck by blocking the interaction of the sensor protein NLRP3 and the adaptor protein ASC. We also found that afatinib was able to alleviate the LPS-induced sepsis in vivo. Conclusion: Our study found that afatinib could inhibit the activation of NLRP3 inflammasome in macrophage, providing new evidence that afatinib could target the innate immune system to control chronic inflammation. These investigations will provide significant experimental evidence in afatinib as therapeutic drug for non-small cell lung cancer or other tumors and NLRP3-related diseases and will explore new targets for afatinib.

Keywords: inflammasome, afatinib, inflammation, tyrosine kinase inhibitor

Procedia PDF Downloads 118

Authors: Fadilah Aleanizy

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Colicins are a family of bacterial toxins that kill Escherichia coli and other closely related species. The mode of action of colicins involves binding to an outer membrane receptor and translocation across the cell envelope, leading to cytotoxicity through specific targets. The mechanism of colicin cytotoxicity includes a non-specific endonuclease activity or depolarization of the cytoplasmic membrane by pore-forming activity. For Group A colicins, translocation requires an interaction between the N-terminal domain of the colicin and a series of membrane- bound and periplasmic proteins known as the Tol system (TolB, TolR, TolA, TolQ, and Pal and the active domain must be translocated through the outer membranes. Protein-protein interactions are intrinsic to virtually every cellular process. The transient protein-protein interactions of the colicin include the interaction with much more complicated assemblies during colicin translocation across the cellular membrane to its target. The potassium release assay detects variation in the K+ content of bacterial cells (K+in). This assays is used to measure the effect of pore-forming colicins such as ColA on an indicator organism by measuring the changes of the K+ concentration in the external medium (K+out ) that are caused by cell killing with a K+ selective electrode. One of the goals of this work is to employ a quantifiable in-vivo method to spot which Tol protein are more implicated in the interaction with colicin A as it is translocated to its target.

Keywords: K+ efflux, Colicin A, Tol-proteins, E. coli

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Authors: Tie-Qing Zhang, Seunghun Jung, Young-Bae Kim

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This research is devoted to developing a membrane reactor to flexibly meet the hydrogen demand of onboard fuel cells, which is an important part of green energy development. Among many renewable chemical products, dimethyl ether (DME) has the advantages of low reaction temperature (400 °C in this study), high hydrogen atom content, low toxicity, and easy preparation. Autothermal reforming, on the other hand, has a high hydrogen recovery rate and exhibits thermal neutrality during the reaction process, so the additional heat source in the hydrogen production process can be omitted. Therefore, the DME auto thermal reforming process was adopted in this study. To control the temperature of the reaction catalyst bed and hydrogen production rate, a Model Predictive Control (MPC) scheme was designed. Taking the above two variables as the control objectives, stable operation of the reformer can be achieved by controlling the flow rates of DME, steam, and high-purity air in real-time. To prevent catalyst poisoning in the fuel cell, the hydrogen needs to be purified to reduce the carbon monoxide content to below 50 ppm. Therefore, a Pd-Ag hydrogen semi-permeable membrane with a thickness of 3-5 μm was inserted into the auto thermal reactor, and the permeation efficiency of hydrogen was improved by steam purging on the permeation side. Finally, hydrogen with a purity of 99.99 was obtained.

Keywords: hydrogen production, auto thermal reforming, membrane, fuel cell

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Authors: Hiripurage Mallika Sandamali Dissanayaka

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Butterflies are found everywhere on Earth, helping flowering plants reproduce through pollination. Wetlands perform many valuable functions such as providing wildlife habitat. Diyasaru Wetland Park was chosen as the study site. It is located in a highly urbanized area of Sri Jayawardenepura Kotte, Sri Lanka. A distribution map was prepared to increase butterfly habitat in the urbanized area, and research was conducted to determine the most suitable sections for using it. As this wetland has footpaths for walking, line transect surveys were used to mark species within the sampling area, and directly observed species were recorded. All data collection was done from 0900 to 1200 hours and 1300 to 1600 hours and fieldwork was done from 11 February 2020 to 20 January 2021. ED binoculars (10.5x45), DSLR cameras (Canon EOS/EFS5 mm 3.5-5.6), and Garmin GPS (Etrex 10) were used to observe butterfly species, identify locations, and take photographs as evidence. Analyzing their habitats using GIS (ArcGIS Pro) to identify their distribution within the park premises, the distribution density of the known size of the population was calculated for each point by kernel density, and local similarity values were calculated for each pair of corresponding features through hotspot analysis, and cell values were determined by inverse distance weighting (IDW) using a linearly weighted combination of a set of sample points. According to the maps prepared to predict the distribution of butterflies in this park, the high level of distribution or favorable areas were near flower gardens and meadows, but some individual species prefer habitats that are more suitable for their life activities, so they live in other areas. Sixty-six (66) species belonging to six (6) families have been recorded in the premises. Sixty (60) species of least concern (LC), two (2) near threatened (NT), and four (4) vulnerable (VU) species have been recorded, and several new species, such as Plum Judy (Abisara echerius), were reported. The outcome of the study will form the basis for decision-making by the Sri Lanka Land Development (SLLD) Corporation for the future development and maintenance of the park.

Keywords: wetland, Lepidoptera, habitat, urban, west

Procedia PDF Downloads 49

Authors: Emma R. Arakelova, Stepan G. Grigoryan, Flora G. Arsenyan, Nelli S. Babayan, Ruzanna M. Grigoryan, Natalia K. Sarkisyan

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Novel nanosize zinc oxide composites of doxorubicin obtained by deposition of 180 nm thick zinc oxide film on the drug surface using DC-magnetron sputtering of a zinc target in the form of gels (PEO+Dox+ZnO and Starch+NaCMC+Dox+ZnO) were studied for drug delivery applications. The cancer specificity was revealed both in in vitro and in vivo models. The cytotoxicity of the test compounds was analyzed against human cancer (HeLa) and normal (MRC5) cell lines using MTT colorimetric cell viability assay. IC50 values were determined and compared to reveal the cancer specificity of the test samples. The mechanistic study of the most active compound was investigated using Flow cytometry analyzing of the DNA content after PI (propidium iodide) staining. Data were analyzed with Tree Star FlowJo software using cell cycle analysis Dean-Jett-Fox module. The in vivo anticancer activity estimation experiments were carried out on mice with inoculated ascitic Ehrlich’s carcinoma at intraperitoneal introduction of doxorubicin and its zinc oxide compositions. It was shown that the nanosize zinc oxide film deposition on the drug surface leads to the selective anticancer activity of composites at the cellular level with the range of selectivity index (SI) from 4 (Starch+NaCMC+Dox+ZnO) to 200 (PEO(gel)+Dox+ZnO) which is higher than that of free Dox (SI = 56). The significant increase in vivo antitumor activity (by a factor of 2-2.5) and decrease of general toxicity of zinc oxide compositions of doxorubicin in the form of the above mentioned gels compared to free doxorubicin were shown on the model of inoculated Ehrlich's ascitic carcinoma. Mechanistic studies of anticancer activity revealed the cytostatic effect based on the high level of DNA biosynthesis inhibition at considerable low concentrations of zinc oxide compositions of doxorubicin. The results of studies in vitro and in vivo behavior of PEO+Dox+ZnO and Starch+NaCMC+Dox+ZnO composites confirm the high potential of the nanosize zinc oxide composites as a vector delivery system for future application in cancer chemotherapy.

Keywords: anticancer activity, cancer specificity, doxorubicin, zinc oxide

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Authors: Adeel Zulifqar, Hong Hu

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Auxetic fabrics are a special kind of textile materials which possess negative Poisson’s ratio. Opposite to most of the conventional fabrics, auxetic fabrics get bigger in the transversal direction when stretched or get smaller when compressed. Auxetic fabrics are superior to conventional fabrics because of their counterintuitive properties, such as enhanced porosity under the extension, excellent formability to a curved surface and high energy absorption ability. Up till today, auxetic fabrics have been produced based on two approaches. The first approach involves using auxetic fibre or yarn and weaving technology to fabricate auxetic fabrics. The other method to fabricate the auxetic fabrics is by using non-auxetic yarns. This method has gained extraordinary curiosity of researcher in recent years. This method is based on realizing auxetic geometries into the fabric structure. In the woven fabric structure auxetic geometries can be realized by creating a differential shrinkage phenomenon into the fabric structural unit cell. This phenomenon can be created by using loose and tight weave combinations within the unit cell of interlacement pattern along with elastic and non-elastic yarns. Upon relaxation, the unit cell of interlacement pattern acquires a non-uniform shrinkage profile due to different shrinkage properties of loose and tight weaves in designed pattern, and the auxetic geometry is realized. The development of uni-stretch auxetic woven fabrics and bi-stretch auxetic woven fabrics by using this method has already been reported. This study reports the development of another kind of bi-stretch auxetic woven fabric. The fabric is first designed by transforming the auxetic geometry into interlacement pattern and then fabricated, using the available conventional weaving technology and non-auxetic elastic and non-elastic yarns. The tensile tests confirmed that the developed bi-stretch auxetic woven fabrics exhibit negative Poisson’s ratio over a wide range of tensile strain. Therefore, it can be concluded that the auxetic geometry can be realized into the woven fabric structure by creating the phenomenon of differential shrinkage and bi-stretch woven fabrics made of non-auxetic yarns having auxetic behavior and stretchability are possible can be obtained. Acknowledgement: This work was supported by the Research Grants Council of Hong Kong Special Administrative Region Government (grant number 15205514).

Keywords: auxetic, differential shrinkage, negative Poisson's ratio, weaving, stretchable

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Authors: M. Hossain, H. P. Zhu, A. B. Yu

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This paper presents a numerical investigation of regime transition of flow of ellipsoidal particles and a comparison with that of spherical particle assembly. Particle assemblies constituting spherical and ellipsoidal particle of 2.5:1 aspect ratio are examined at separate instances in similar flow conditions in a shear cell model that is numerically developed based on the discrete element method. Correlations among elastically scaled stress, kinetically scaled stress, coordination number and volume fraction are investigated, and show important similarities and differences for the spherical and ellipsoidal particle assemblies. In particular, volume fractions at points of regime transition are identified for both types of particles. It is found that compared with spherical particle assembly, ellipsoidal particle assembly has higher volume fraction for the quasistatic to intermediate regime transition and lower volume fraction for the intermediate to inertial regime transition. Finally, the relationship between coordination number and volume fraction shows strikingly distinct features for the two cases, suggesting that different from spherical particles, the effect of the shear rate on the coordination number is not significant for ellipsoidal particles. This work provides a glimpse of currently running work on one of the most attractive scopes of research in this field and has a wide prospect in understanding rheology of more complex shaped particles in light of the strong basis of simpler spherical particle rheology.

Keywords: DEM, granular rheology, non-spherical particles, regime transition

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Authors: T. H. Huang, C. L. Fern, Y. K. Tseng

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The design and reliability of solar photovoltaic modules are crucial to the development of solar energy, and efforts are still being made to extend the life of photovoltaic modules to improve their efficiency because natural aging is time-consuming and does not provide manufacturers and investors with timely information, accelerated aging is currently the best way to estimate the life of photovoltaic modules. Bifacial solar cells not only absorb light from the front side but also absorb light reflected from the ground on the back side, surpassing the performance of single-sided solar cells. Due to the asymmetry of the two sides of the light, in addition to the difference in photovoltaic conversion efficiency, there will also be differences in heat distribution, which will affect the electrical properties and material structure of the bifacial solar cell itself. In this study, there are two types of experimental samples: packaged and unpackaged and then irradiated with UVC light sources and halogen lamps for accelerated aging, as well as a control group without aging. After two weeks of accelerated aging, the bifacial solar cells were visual observation, and infrared thermal images were taken; then, the samples were subjected to IV measurement, and samples were taken for SEM, Raman, and XRD analyses in order to identify the defects that lead to failure and chemical changes, as well as to analyze the reasons for the degradation of their characteristics. From the results of the analysis, it is found that aging will cause carbonization of the polymer material on the surface of bifacial solar cells, and the crystal structure will be affected.

Keywords: bifacial solar cell, accelerated aging, temperature, characterization, electrical measurement

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Authors: S. D. Abdul, F. B. J. Sawa, D. Z. Andrawus, G. Dan'ilu

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Fresh leaves of twelve accessions of S. indicum were studied to examine their stomatal features, trichomes, epidermal cell shapes and anticlinal cell-wall patterns which may be used for the delimitation of the varieties. The twelve accessions of S. indicum studied have amphistomatic leaves, i.e. having stomata on both surfaces. Four types of stomatal complex types were observed namely, diacytic, anisocytic, tetracytic and anomocytic. Anisocytic type was the most common occurring on both surfaces of all the varieties and occurred 100% in varieties lale-duk, ex-sudan and ex-gombe 6. One-way ANOVA revealed that there was no significant difference between the stomatal densities of ex-gombe 6, ex-sudan, adawa-wula, adawa-ting, ex-gombe 4 and ex-gombe 2 . Accession adawa-ting (improved) has the smallest stomatal size (26.39µm) with highest stomatal density (79.08mm2) while variety adawa-wula possessed the largest stomatal size (74.31µm) with lowest stomatal density (29.60mm2), the exception was found in variety adawa-ting whose stomatal size is larger (64.03µm) but with higher stomatal density (71.54mm2). Wavy, curve or undulate anticlinal wall patterns with irregular and or isodiametric epidermal cell shapes were observed. These accessions were found to exhibit high degree of heterogeneity in their trichome features. Ten types of trichomes were observed: unicellular, glandular peltate, capitate glandular, long unbranched uniseriate, short unbranched uniseriate, scale, multicellular, multiseriate capitate glandular, branched uniseriate and stallate trichomes. The most frequent trichome type is short-unbranched uniseriate, followed by long-unbranched uniseriate (72.73% and 72.5%) respectively. The least frequent was multiseriate capitate glandular (11.5%). The high variation in trichome types and density coupled with the stomatal complex types suggest that these varieties of S. indicum probably have the capacity to conserve water. Furthermore, the leaf micromorphological features varied from one accession to another, hence, are found to be good diagnostic and additional tool in identification as well as nomenclature of the accessions of S. indicum.

Keywords: Sesamum indicum, stomata, trichomes, epidermal cells, taxonomy

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Authors: Seon-Young Lee, Harkiran Sagoo, Katherine Whitehurst, Georgina Wellstead, Alexander Fowler, Riaz Agha, Dennis Orgill

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Introduction: Systematic reviews attempt to answer research questions by synthesising the data within primary papers. They are an increasingly important tool within evidence-based medicine, guiding clinical practice, future research and healthcare policy. We sought to determine the reporting quality of recent systematic reviews in plastic surgery. Methods: This systematic review was conducted in line with the Cochrane handbook, reported in line with the PRISMA statement and registered at the ResearchRegistry (UIN: reviewregistry18). MEDLINE and EMBASE databases were searched in 2013 and 2014 for systematic reviews by five major plastic surgery journals. Screening, identification and data extraction was performed independently by two teams. Results: From an initial set of 163 articles, 79 met the inclusion criteria. The median PRISMA score was 16 out of 27 items (59.3%; range 6-26, 95% CI 14-17). Compliance between individual PRISMA items showed high variability. It was poorest for items related to the use of review protocol (item 5; 5%) and presentation of data on risk of bias of each study (item 19; 18%), while being the highest for description of rationale (item 3; 99%) and sources of funding and other support (item 27; 95%), and for structured summary in the abstract (item 2; 95%). Conclusion: The reporting quality of systematic reviews in plastic surgery requires improvement. ‘Hard-wiring’ of compliance through journal submission systems, as well as improved education, awareness and a cohesive strategy among all stakeholders is called for.

Keywords: PRISMA, reporting quality, plastic surgery, systematic review, meta-analysis

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Authors: Koe Han Beng, Khoo Boo Cheong

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The rising interest of stepped hull design has been led by the demand of more efficient high-speed boat. At the same time, the need of accurate prediction method for stepped planing hull is getting more important. By understanding the flow at high Froude number is the key in designing a practical step hull, the study surrounding stepped hull has been done mainly in the towing tank which is time-consuming and costly for initial design phase. Here the feasibility of predicting hydrodynamics of high-speed planing hull both with and without step using computational fluid dynamics (CFD) with the volume of fluid (VOF) methodology is studied in this work. First the flow around the prismatic body is analyzed, the force generated and its center of pressure are compared with available experimental and empirical data from the literature. The wake behind the transom on the keel line as well as the quarter beam buttock line are then compared with the available data, this is important since the afterbody flow of stepped hull is subjected from the wake of the forebody. Finally the calm water performance prediction of a conventional planing hull and its stepped version is then analyzed. Overset mesh methodology is employed in solving the dynamic equilibrium of the hull. The resistance, trim, and heave are then compared with the experimental data. The resistance is found to be predicted well and the dynamic equilibrium solved by the numerical method is deemed to be acceptable. This means that computational fluid dynamics will be very useful in further study on the complex flow around stepped hull and its potential usage in the design phase.

Keywords: planing hulls, stepped hulls, wake shape, numerical simulation, hydrodynamics

Procedia PDF Downloads 282

Authors: Jeet Chakraborty, Sanjay Dutta

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Antibiotic resistance by bacteria has proved to be a severe threat to mankind in recent times, and this fortifies an urgency to design and develop potent antibacterial small molecules/compounds with nonconventional mechanisms than the conventional ones. DNA carries the genetic signature of any organism, and bacteria maintain their genomic DNA inside the cell in a well-regulated compact form with the help of various nucleoid associated proteins like HU, HNS, etc. These proteins control various fundamental processes like gene expression, replication, etc., inside the cell. Alteration of the native DNA structure of bacteria can lead to severe consequences in cellular processes inside the bacterial cell that ultimately result in the death of the organism. The change in the global DNA structure by small molecules initiates a plethora of cellular responses that have not been very well investigated. Echinomycin and Triostin-A are biologically active Quinoxaline small molecules that typically consist of a quinoxaline chromophore attached with an octadepsipeptide ring. They bind to double-stranded DNA in a sequence-specific way and have high activity against a wide variety of bacteria, mainly against Gram-positive ones. To date, few synthetic quinoxaline scaffolds were synthesized, displaying antibacterial potential against a broad scale of pathogenic bacteria. QNOs (Quinoxaline N-oxides) are known to target DNA and instigate reactive oxygen species (ROS) production in bacteria, thereby exhibiting antibacterial properties. The divergent role of Quinoxaline small molecules in medicinal research qualifies them for the evaluation of their antimicrobial properties as a potential candidate. The previous study from our lab has given new insights on a 6-nitroquinoxaline derivative 1d as an intercalator of DNA, which induces conformational changes in DNA upon binding.7 The binding event observed was dependent on the presence of a crucial benzyl substituent on the quinoxaline moiety. This was associated with a large induced CD (ICD) appearing in a sigmoidal pattern upon the interaction of 1d with dsDNA. The induction of DNA superstructures by 1d at high Drug:DNA ratios was observed that ultimately led to DNA condensation. Eviction of invitro-assembled nucleosome upon treatment with a high dose of 1d was also observed. In this work, monoquinoxaline derivatives of 1d were synthesized by various modifications of the 1d scaffold. The set of synthesized 6-nitroquinoxaline derivatives along with 1d were all subjected to antibacterial evaluation across five different bacteria species. Among the compound set, 3a displayed potent antibacterial activity against Staphylococcus aureus bacteria. 3a was further subjected to various biophysical studies to check whether the DNA structural alteration potential was still intact. The biological response of S. aureus cells upon treatment with 3a was studied using various cell biology processes, which led to the conclusion that 3d can initiate DNA damage in the S. aureus cells. Finally, the potential of 3a in disrupting preformed S.aureus and S.epidermidis biofilms was also studied.

Keywords: DNA structural change, antibacterial, intercalator, DNA superstructures, biofilms

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Authors: Andres Manuel Garcia Lamparte, Rocio Losada Iglesias, Marcos BoullóN Magan, David Miranda Barros

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The biodiversity strategy of the European Union for 2030, mentions climate change as one of the key factors for biodiversity loss and considers green infrastructure as one of the solutions to this problem. In this line, the European Commission has developed a green infrastructure strategy which commits members states to consider green infrastructure in their territorial planning. This green infrastructure is aimed at granting the provision of a wide number of ecosystem services to support biodiversity and human well-being by countering the effects of climate change. Yet, there are not too many tools available to delimit green infrastructure. The available ones consider the potential of the territory to provide ecosystem services. However, these methods usually aggregate several maps of ecosystem services potential without considering possible trade-offs. This can lead to excluding areas with a high potential for providing ecosystem services which have many trade-offs with other ecosystem services. In order to tackle this problem, a methodology is proposed to consider ecosystem services trade-offs in the objective function of a simulated annealing algorithm aimed at delimiting green infrastructure multifunctional buffer areas. To this end, the provision potential maps of the regulating ecosystem services considered to delimit the multifunctional buffer areas are clustered in groups, so that ecosystem services that create trade-offs are excluded in each group. The normalized provision potential maps of the ecosystem services in each group are added to obtain a potential map per group which is normalized again. Then the potential maps for each group are combined in a raster map that shows the highest provision potential value in each cell. The combined map is then used in the objective function of the simulated annealing algorithm. The algorithm is run both using the proposed methodology and considering the ecosystem services individually. The results are analyzed with spatial statistics and landscape metrics to check the number of ecosystem services that the delimited areas produce, as well as their regularity and compactness. It has been observed that the proposed methodology increases the number of ecosystem services produced by delimited areas, improving their multifunctionality and increasing their effectiveness in preventing climate change impacts.

Keywords: ecosystem services trade-offs, green infrastructure delineation, multifunctional buffer areas, climate change

Procedia PDF Downloads 174

Authors: Kiran Shehzadi, Yasmeen Akhtar, Mujahid Ameen, Tabinda Ijaz, Shoukat Siddique

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Nanoparticles, due to their different sizes and morphologies, are employed in various fields such as the medical field, cosmetics, pharmaceutical, textile industry as well as in paints, adhesives, and electronics. Metal nanoparticles exhibit excellent antimicrobial activity, dye degradation and can be used as anti-cancerous drug loading agents. In this study, sZilver nanoparticles (Ag-NPs) were synthesized employing doxycycline (antibiotic) as a reducing and capping agent (biological/green synthesis). Produced Ag-NPS were characterized using UV/VIS spectrophotometry, XRD, SEM, and FTIR. Surface plasmon resonance (SPR) of silver nanoparticles was observed at 411nm with 90nm size with homogenized spherical shape. These particles revealed good inhibition zones for Fungi such as Candida albicans and Candida tropicalis. In this study, toxic properties of Ag-NPs were monitored by allowing them to penetrate in the cell, causing an abrupt increase in oxidative stress, which resulted ultimately in cell death. Histopathological analysis of mice organs was performed by administering definite concentrations of silver nanoparticles orally to mice for 14 days. Toxic properties were determined, and it was revealed that the toxicity of silver nanoparticles mainly depends on the size. Silver nanoparticles of this work presented mild toxicity for different organs (liver, kidney, spleen, heart, and stomach) of mice.

Keywords: metal nanoparticles, green/biological methods, toxicity, Candida albicans, Candida tropicalis

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Authors: Malgorzata J. Rybak-Smith, Benedicte Thiebaut, Simon Johnson, Peter Bishop, Helen E. Townley

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Gadolinium doped titania (TiO2:Gd) nanoparticles (NPs) can be activated by X-ray radiation to generate Reactive Oxygen Species (ROS), which can be effective in killing cancer cells. As such, treatment with these NPs can be used to enhance the efficacy of conventional radiotherapy. Incorporation of the NPs in to tumour tissue will permit the extension of radiotherapy to currently untreatable tumours deep within the body, and also reduce damage to neighbouring healthy cells. In an attempt to find a fast and scalable method for the synthesis of the TiO2:Gd NPs, the use of Flame Spray Pyrolysis (FSP) was investigated. A series of TiO2 NPs were generated with 1, 2, 5 and 7 mol% gadolinium dopant. Post-synthesis, the TiO2:Gd NPs were silica-coated to improve their biocompatibility. Physico-chemical characterisation was used to determine the size and stability in aqueous suspensions of the NPs. All analysed TiO2:Gd NPs were shown to have relatively high photocatalytic activity. Furthermore, the FSP synthesized silica-coated TiO2:Gd NPs generated enhanced ROS in chemico. Studies on rhabdomyosarcoma (RMS) cell lines (RD & RH30) demonstrated that in the absence of irradiation all TiO2:Gd NPs were inert. However, application of TiO2:Gd NPs to RMS cells, followed by irradiation, showed a significant decrease in cell proliferation. Consequently, our studies showed that the X-ray-activatable TiO2:Gd NPs can be prepared by a high-throughput scalable technique to provide a novel and affordable anticancer therapy.

Keywords: cancer, gadolinium, ROS, titania nanoparticles, X-ray

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Authors: Mokhtar Azizi

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Due to heavy traffic and congested roads, it is crucial that the most popular main public transport services in Kuala Lumpur i.e. Putra LRT, Star LRT, KTM Commuter, KL Monorail and Rapid Bus must be continuously monitored and improved to fulfill the rider’s requirement and kept updated by the transit agencies. Evaluation on the current status of the services has been determined out by calculating the transit supportive area (TSA) and level of service (LOS) for each transit station. This research study has carried out the TSA and LOS mapping based on GIS techniques. The detailed census data of the region along the line of services has been collected from the Department of Statistics Malaysia for this purpose. The service coverage has been decided by 400 meters buffer zone for bus stations and 800 meters for rails station and railways in measurement the Quality of Service along the line of services. All the required information has been calculated by using the customized GIS software called Kuala Lumpur Transit Information System (KLTIS). The transit supportive area was calculated with the employment density at least 10 job/hectare or household density at 7.5 unit/hectare and total area covered by transit supportive area is 22516 hectare and the total area that is not supported by transit is 1718 hectare in Kuala Lumpur. The level of service is calculated with the percentage of transit supportive area served by transit for each station. In overall the percentage transit supportive areas served by transit for all the stations were less than 50% which falls in a very low level of service category. This research has proven its benefit by providing the current transit services operators with vital information for improvement of existing public transport services.

Keywords: service coverage, transit supportive area, level of service, transit system

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Authors: Aida Kalantari, Boyang Ji, Tao Chen, Ivan Mijakovic

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3-hydroxypropanoic acid (3-HP) is one of the most important biomass-derivable platform chemicals that can be converted into a number of industrially important compounds. There have been several attempts at production of 3-HP from renewable sources in cell factories, focusing mainly on Escherichia coli, Klebsiella pneumoniae, and Saccharomyces cerevisiae. Despite the significant progress made in this field, commercially exploitable large-scale production of 3-HP in microbial strains has still not been achieved. In this study, we investigated the potential of Bacillus subtilis to be used as a microbial platform for bioconversion of glycerol into 3-HP. Our recombinant B. subtilis strains overexpress the two-step heterologous pathway containing glycerol dehydratase and aldehyde dehydrogenase from various backgrounds. The recombinant strains harboring the codon-optimized synthetic pathway from K. pneumoniae produced low levels of 3-HP. Since the enzymes in the heterologous pathway are sensitive to oxygen, we had to perform our experiments in micro-aerobic conditions. Under these conditions, the cell produces lactate in order to regenerate NAD+, and we found the lactate production to be in competition with the production of 3-HP. Therefore, based on the in silico predictions, we knocked out the glycerol kinase (glpk), which in combination with growth on glucose, resulted in improving the 3-HP titer to 1 g/L and the removal of lactate. Cultivation of the same strain in an enriched medium improved the 3-HP titer up to 7.6 g/L. Our findings provide the first report of successful introduction of the biosynthetic pathway for conversion of glycerol into 3-HP in B. subtilis.

Keywords: bacillus subtilis, glycerol, 3-hydroxypropanoic acid, metabolic engineering

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Authors: Aminu Bashir Mohammad, Agwu Ezera, Abdulrazaq G. Habib, Garba Iliyasu

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Background: Drug resistance tuberculosis (DR-TB) continues to be a challenge in developing countries with poor resources. Routine screening for primary DR-TB before commencing treatment is not done in public hospitals in Nigeria, even with the large body of evidence that shows a high prevalence of primary DR-TB. Data on drug resistance and its genetic determinant among follow up TB patients is lacking in Nigeria. Hence the aim of this study was to determine the prevalence and genetic determinant of drug resistance among follow up TB patients in a tertiary hospital in Nigeria. Methods: This was a cross-sectional laboratory-based study conducted on 384 sputum samples collected from consented follow-up tuberculosis patients. Standard microbiology methods (Zeil-Nielsen staining and microscopy) and PCR (Line Probe Assay)] were used to analyze the samples collected. Person’s Chi-square was used to analyze the data generated. Results: Out of three hundred and eighty-four (384) sputum samples analyzed for mycobacterium tuberculosis (MTB) and DR-TB twenty-five 25 (6.5%) were found to be AFB positive. These samples were subjected to PCR (Line Probe Assay) out of which 18(72%) tested positive for DR-TB. Mutations conferring resistance to rifampicin (rpo B) and isoniazid (katG, and or inhA) were detected in 12/18(66.7%) and 6/18(33.3%), respectively. Transmission dynamic of DR-TB was not significantly (p>0.05) dependent on demographic characteristics. Conclusion: There is a need to strengthened the laboratory capacity for diagnosis of TB and drug resistance testing and make these services available, affordable, and accessible to the patients who need them.

Keywords: drug resistance tuberculosis, genetic determinant, intensive phase, Nigeria

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Authors: Arati Inamdar, Siddharth Bhattacharyya, Kester Haye

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Collision tumors are rare entities characterized by neoplasms of two different cell populations with distinct separating boundaries. Such tumors could be benign, malignant, or a combination of both. The exact mechanism of origin for collision tumors is predicted to be tumor heterogeneity or concurrent occurrence of neoplasm in the same organ. We present two cases of plasmacytoma presenting as a collision tumor, one with a tumor of hematological origin and another with a non-hematological origin, namely Chronic Lymphocytic Leukemia and Adenocarcinoma of the colon, respectively. The immunohistochemical stains and flowcytometry analysis performed on the specimens aided incorrect diagnosis. Interestingly, neoplastic cells of plasmacytoma in the first case demonstrated strong cytokeratin along with weak Epithelial Specific Antigen/ Epithelial cell adhesion molecule Monoclonal Antibody (MOC31) positivity, indicating that the tumor may influence the microenvironment of the tumor in the vicinity. Furthermore, the next-generation sequencing studies performed on the specimen with plasmacytoma and chronic lymphocytic lymphoma demonstrated BReast CAncer gene (BRCA2) and Tumor Necrosis Factor Alpha Induced Protein 3 (TNFAIP3) as a disease associated variants suggestive of risk for multiple tumors including collision tumors. Our reports highlight the unique collision tumors involving plasmacytoma, which have never been reported previously, as well as provide necessary insights about the underline genetic aberrations and tumor heterogeneity through sequencing studies and allow clonality assessment for subsequent tumors.

Keywords: BRCA2, collision tumor, chronic lymphocytic leukemia, plasmacytoma

Procedia PDF Downloads 190