Search results for: porphyrins synthesis and modification
Commenced in January 2007
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Paper Count: 3061

Search results for: porphyrins synthesis and modification

151 Fe3O4 Decorated ZnO Nanocomposite Particle System for Waste Water Remediation: An Absorptive-Photocatalytic Based Approach

Authors: Prateek Goyal, Archini Paruthi, Superb K. Misra

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Contamination of water resources has been a major concern, which has drawn attention to the need to develop new material models for treatment of effluents. Existing conventional waste water treatment methods remain ineffective sometimes and uneconomical in terms of remediating contaminants like heavy metal ions (mercury, arsenic, lead, cadmium and chromium); organic matter (dyes, chlorinated solvents) and high salt concentration, which makes water unfit for consumption. We believe that nanotechnology based strategy, where we use nanoparticles as a tool to remediate a class of pollutants would prove to be effective due to its property of high surface area to volume ratio, higher selectivity, sensitivity and affinity. In recent years, scientific advancement has been made to study the application of photocatalytic (ZnO, TiO2 etc.) nanomaterials and magnetic nanomaterials in remediating contaminants (like heavy metals and organic dyes) from water/wastewater. Our study focuses on the synthesis and monitoring remediation efficiency of ZnO, Fe3O4 and Fe3O4 coated ZnO nanoparticulate system for the removal of heavy metals and dyes simultaneously. Multitude of ZnO nanostructures (spheres, rods and flowers) using multiple routes (microwave & hydrothermal approach) offers a wide range of light active photo catalytic property. The phase purity, morphology, size distribution, zeta potential, surface area and porosity in addition to the magnetic susceptibility of the particles were characterized by XRD, TEM, CPS, DLS, BET and VSM measurements respectively. Further on, the introduction of crystalline defects into ZnO nanostructures can also assist in light activation for improved dye degradation. Band gap of a material and its absorbance is a concrete indicator for photocatalytic activity of the material. Due to high surface area, high porosity and affinity towards metal ions and availability of active surface sites, iron oxide nanoparticles show promising application in adsorption of heavy metal ions. An additional advantage of having magnetic based nanocomposite is, it offers magnetic field responsive separation and recovery of the catalyst. Therefore, we believe that ZnO linked Fe3O4 nanosystem would be efficient and reusable. Improved photocatalytic efficiency in addition to adsorption for environmental remediation has been a long standing challenge, and the nano-composite system offers the best of features which the two individual metal oxides provide for nanoremediation.

Keywords: adsorption, nanocomposite, nanoremediation, photocatalysis

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150 Synthesis, Molecular Modeling and Study of 2-Substituted-4-(Benzo[D][1,3]Dioxol-5-Yl)-6-Phenylpyridazin-3(2H)-One Derivatives as Potential Analgesic and Anti-Inflammatory Agents

Authors: Jyoti Singh, Ranju Bansal

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Fighting pain and inflammation is a common problem faced by physicians while dealing with a wide variety of diseases. Since ancient time nonsteroidal anti-inflammatory agents (NSAIDs) and opioids have been the cornerstone of treatment therapy, however, the usefulness of both these classes is limited due to severe side effects. NSAIDs, which are mainly used to treat mild to moderate inflammatory pain, induce gastric irritation and nephrotoxicity whereas opioids show an array of adverse reactions such as respiratory depression, sedation, and constipation. Moreover, repeated administration of these drugs induces tolerance to the analgesic effects and physical dependence. Further discovery of selective COX-2 inhibitors (coxibs) suggested safety without any ulcerogenic side effects; however, long-term use of these drugs resulted in kidney and hepatic toxicity along with an increased risk of secondary cardiovascular effects. The basic approaches towards inflammation and pain treatment are constantly changing, and researchers are continuously trying to develop safer and effective anti-inflammatory drug candidates for the treatment of different inflammatory conditions such as osteoarthritis, rheumatoid arthritis, ankylosing spondylitis, psoriasis and multiple sclerosis. Synthetic 3(2H)-pyridazinones constitute an important scaffold for drug discovery. Structure-activity relationship studies on pyridazinones have shown that attachment of a lactam at N-2 of the pyridazinone ring through a methylene spacer results in significantly increased anti-inflammatory and analgesic properties of the derivatives. Further introduction of the heterocyclic ring at lactam nitrogen results in improvement of biological activities. Keeping in mind these SAR studies, a new series of compounds were synthesized as shown in scheme 1 and investigated for anti-inflammatory, analgesic, anti-platelet activities and docking studies. The structures of newly synthesized compounds have been established by various spectroscopic techniques. All the synthesized pyridazinone derivatives exhibited potent anti-inflammatory and analgesic activity. Homoveratryl substituted derivative was found to possess highest anti-inflammatory and analgesic activity displaying 73.60 % inhibition of edema at 40 mg/kg with no ulcerogenic activity when compared to standard drugs indomethacin. Moreover, 2-substituted-4-benzo[d][1,3]dioxole-6-phenylpyridazin-3(2H)-ones derivatives did not produce significant changes in bleeding time and emerged as safe agents. Molecular docking studies also illustrated good binding interactions at the active site of the cyclooxygenase-2 (hCox-2) enzyme.

Keywords: anti-inflammatory, analgesic, pyridazin-3(2H)-one, selective COX-2 inhibitors

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149 High Capacity SnO₂/Graphene Composite Anode Materials for Li-Ion Batteries

Authors: Hilal Köse, Şeyma Dombaycıoğlu, Ali Osman Aydın, Hatem Akbulut

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Rechargeable lithium-ion batteries (LIBs) have become promising power sources for a wide range of applications, such as mobile communication devices, portable electronic devices and electrical/hybrid vehicles due to their long cycle life, high voltage and high energy density. Graphite, as anode material, has been widely used owing to its extraordinary electronic transport properties, large surface area, and high electrocatalytic activities although its limited specific capacity (372 mAh g-1) cannot fulfil the increasing demand for lithium-ion batteries with higher energy density. To settle this problem, many studies have been taken into consideration to investigate new electrode materials and metal oxide/graphene composites are selected as a kind of promising material for lithium ion batteries as their specific capacities are much higher than graphene. Among them, SnO₂, an n-type and wide band gap semiconductor, has attracted much attention as an anode material for the new-generation lithium-ion batteries with its high theoretical capacity (790 mAh g-1). However, it suffers from large volume changes and agglomeration associated with the Li-ion insertion and extraction processes, which brings about failure and loss of electrical contact of the anode. In addition, there is also a huge irreversible capacity during the first cycle due to the formation of amorphous Li₂O matrix. To obtain high capacity anode materials, we studied on the synthesis and characterization of SnO₂-Graphene nanocomposites and investigated the capacity of this free-standing anode material in this work. For this aim, firstly, graphite oxide was obtained from graphite powder using the method described by Hummers method. To prepare the nanocomposites as free-standing anode, graphite oxide particles were ultrasonicated in distilled water with SnO2 nanoparticles (1:1, w/w). After vacuum filtration, the GO-SnO₂ paper was peeled off from the PVDF membrane to obtain a flexible, free-standing GO paper. Then, GO structure was reduced in hydrazine solution. Produced SnO2- graphene nanocomposites were characterized by scanning electron microscopy (SEM), energy dispersive X-ray spectrometer (EDS), and X-ray diffraction (XRD) analyses. CR2016 cells were assembled in a glove box (MBraun-Labstar). The cells were charged and discharged at 25°C between fixed voltage limits (2.5 V to 0.2 V) at a constant current density on a BST8-MA MTI model battery tester with 0.2C charge-discharge rate. Cyclic voltammetry (CV) was performed at the scan rate of 0.1 mVs-1 and electrochemical impedance spectroscopy (EIS) measurements were carried out using Gamry Instrument applying a sine wave of 10 mV amplitude over a frequency range of 1000 kHz-0.01 Hz.

Keywords: SnO₂-graphene, nanocomposite, anode, Li-ion battery

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148 Biocompatibility of Calcium Phosphate Coatings With Different Crystallinity Deposited by Sputtering

Authors: Ekaterina S. Marchenko, Gulsharat A. Baigonakova, Kirill M. Dubovikov, Igor A. Khlusov

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NiTi alloys combine biomechanical and biochemical properties. This makes them a perfect candidate for medical applications. However, there is a serious problem with these alloys, such as the release of Ni from the matrix. Ni ions are known to be toxic to living tissues and leach from the matrix into the surrounding implant tissues due to corrosion after prolonged use. To prevent the release of Ni ions, corrosive strong coatings are usually used. Titanium nitride-based coatings are perfect corrosion inhibitors and also have good bioactive properties. However, there is an opportunity to improve the biochemical compatibility of the surface by depositing another layer. This layer can consist of elements such as calcium and phosphorus. The Ca and P ions form different calcium phosphate phases, which are present in the mineral part of human bones. We therefore believe that these elements must promote osteogenesis and osteointegration. In view of the above, the aim of this study is to investigate the effect of crystallinity on the biocompatibility of a two-layer coating deposited on NiTi substrate by sputtering. The first step of the research, apart from the NiTi polishing, is the layer-by-layer deposition of Ti-Ni-Ti by magnetron sputtering and the subsequent synthesis of this composite in an N atmosphere at 900 °C. The total thickness of the corrosion resistant layer is 150 nm. Plasma assisted RF sputtering was then used to deposit a bioactive film on the titanium nitride layer. A Ca-P powder target was used to obtain such a film. We deposited three types of Ca-P layers with different crystallinity and compared them in terms of cytotoxicity. One group of samples had no Ca-P coating and was used as a control. We obtained different crystallinity by varying the sputtering parameters such as bias voltage, plasma source current and pressure. XRD analysis showed that all coatings are calcium phosphate, but the sample obtained at maximum bias and plasma source current and minimum pressure has the most intense peaks from the coating phase. SEM and EDS showed that all three coatings have a homogeneous and dense structure without cracks and consist of calcium, phosphorus and oxygen. Cytotoxic tests carried out on three types of samples with Ca-P coatings and a control group showed that the control sample and the sample with Ca-P coating obtained at maximum bias voltage and plasma source current and minimum pressure had the lowest number of dead cells on the surface, around 11 ± 4%. Two other types of samples with Ca-P coating have 40 ± 9% and 21 ± 7% dead cells on the surface. It can therefore be concluded that these two sputtering modes have a negative effect on the corrosion resistance of the whole samples. The third sputtering mode does not affect the corrosion resistance and has the same level of cytotoxicity as the control. It can be concluded that the most suitable sputtering mode is the third with maximum bias voltage and plasma source current and minimum pressure.

Keywords: calcium phosphate coating, cytotoxicity, NiTi alloy, two-layer coating

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147 Schoolwide Implementation of Schema-Based Instruction for Mathematical Problem Solving: An Action Research Investigation

Authors: Sara J. Mills, Sally Howell

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The field of special education has long struggled to bridge the research to practice gap. There is ample evidence from research of effective strategies for students with special needs, but these strategies are not routinely implemented in schools in ways that yield positive results for students. In recent years, the field of special education has turned its focus to implementation science. That is, discovering effective methods of implementing evidence-based practices in school settings. Teacher training is a critical factor in implementation. This study aimed to successfully implement Schema-Based Instruction (SBI) for math problem solving in four classrooms in a special primary school serving students with language deficits, including students with Autism Spectrum Disorders (ASD) and Intellectual Disabilities (ID). Using an action research design that allowed for adjustments and modification to be made over the year-long study, two cohorts of teachers across the school were trained and supported in six-week learning cycles to implement SBI in their classrooms. The learning cycles included a one-day training followed by six weeks of one-on-one or team coaching and three fortnightly cohort group meetings. After the first cohort of teachers completed the learning cycle, modifications and adjustments were made to lesson materials in an attempt to improve their effectiveness with the second cohort. Fourteen teachers participated in the study, including master special educators (n=3), special education instructors (n=5), and classroom assistants (n=6). Thirty-one students participated in the study (21 boys and 10 girls), ranging in age from 5 to 12 years (M = 9 years). Twenty-one students had a diagnosis of ASD, 20 had a diagnosis of mild or moderate ID, with 13 of these students having both ASD and ID. The remaining students had diagnosed language disorders. To evaluate the effectiveness of the implementation approach, both student and teacher data was collected. Student data included pre- and post-tests of math word problem solving. Teacher data included fidelity of treatment checklists and pre-post surveys of teacher attitudes and efficacy for teaching problem solving. Finally, artifacts were collected throughout the learning cycle. Results from cohort 1 and cohort 2 revealed similar outcomes. Students improved in the number of word problems they answered correctly and in the number of problem-solving steps completed independently. Fidelity of treatment data showed that teachers implemented SBI with acceptable levels of fidelity (M = 86%). Teachers also reported increases in the amount of time spent teaching problem solving, their confidence in teaching problem solving and their perception of students’ ability to solve math word problems. The artifacts collected during instruction indicated that teachers made modifications to allow their students to access the materials and to show what they knew. These findings are in line with research that shows student learning can improve when teacher professional development is provided over an extended period of time, actively involves teachers, and utilizes a variety of learning methods in classroom contexts. Further research is needed to evaluate whether these gains in teacher instruction and student achievement can be maintained over time once the professional development is completed.

Keywords: implementation science, mathematics problem solving, research-to-practice gap, schema based instruction

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146 3D Nanostructured Assembly of 2D Transition Metal Chalcogenide/Graphene as High Performance Electrocatalysts

Authors: Sunil P. Lonkar, Vishnu V. Pillai, Saeed Alhassan

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Design and development of highly efficient, inexpensive, and long-term stable earth-abundant electrocatalysts hold tremendous promise for hydrogen evolution reaction (HER) in water electrolysis. The 2D transition metal dichalcogenides, especially molybdenum disulfide attracted a great deal of interests due to its high electrocatalytic activity. However, due to its poor electrical conductivity and limited exposed active sites, the performance of these catalysts is limited. In this context, a facile and scalable synthesis method for fabrication nanostructured electrocatalysts composed 3D graphene porous aerogels supported with MoS₂ and WS₂ is highly desired. Here we developed a highly active and stable electrocatalyst catalyst for the HER by growing it into a 3D porous architecture on conducting graphene. The resulting nanohybrids were thoroughly investigated by means of several characterization techniques to understand structure and properties. Moreover, the HER performance of these 3D catalysts is expected to greatly improve in compared to other, well-known catalysts which mainly benefits from the improved electrical conductivity of the by graphene and porous structures of the support. This technologically scalable process can afford efficient electrocatalysts for hydrogen evolution reactions (HER) and hydrodesulfurization catalysts for sulfur-rich petroleum fuels. Owing to the lower cost and higher performance, the resulting materials holds high potential for various energy and catalysis applications. In typical hydrothermal method, sonicated GO aqueous dispersion (5 mg mL⁻¹) was mixed with ammonium tetrathiomolybdate (ATTM) and tungsten molybdate was treated in a sealed Teflon autoclave at 200 ◦C for 4h. After cooling, a black solid macroporous hydrogel was recovered washed under running de-ionized water to remove any by products and metal ions. The obtained hydrogels were then freeze-dried for 24 h and was further subjected to thermal annealing driven crystallization at 600 ◦C for 2h to ensure complete thermal reduction of RGO into graphene and formation of highly crystalline MoS₂ and WoS₂ phases. The resulting 3D nanohybrids were characterized to understand the structure and properties. The SEM-EDS clearly reveals the formation of highly porous material with a uniform distribution of MoS₂ and WS₂ phases. In conclusion, a novice strategy for fabrication of 3D nanostructured MoS₂-WS₂/graphene is presented. The characterizations revealed that the in-situ formed promoters uniformly dispersed on to few layered MoS₂¬-WS₂ nanosheets that are well-supported on graphene surface. The resulting 3D hybrids hold high promise as potential electrocatalyst and hydrodesulfurization catalyst.

Keywords: electrocatalysts, graphene, transition metal chalcogenide, 3D assembly

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145 Introducing Data-Driven Learning into Chinese Higher Education EAP Writing Instructional Settings

Authors: Jingwen Ou

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Writing for academic purposes in a second or foreign language is one of the most important and the most demanding skills to be mastered by non-native speakers. Traditionally, the EAP writing instruction at the tertiary level encompasses the teaching of academic genre knowledge, more specifically, the disciplinary writing conventions, the rhetorical functions, and specific linguistic features. However, one of the main sources of challenges in English academic writing for L2 students at the tertiary level can still be found in proficiency in academic discourse, especially vocabulary, academic register, and organization. Data-Driven Learning (DDL) is defined as “a pedagogical approach featuring direct learner engagement with corpus data”. In the past two decades, the rising popularity of the application of the data-driven learning (DDL) approach in the field of EAP writing teaching has been noticed. Such a combination has not only transformed traditional pedagogy aided by published DDL guidebooks in classroom use but also triggered global research on corpus use in EAP classrooms. This study endeavors to delineate a systematic review of research in the intersection of DDL and EAP writing instruction by conducting a systematic literature review on both indirect and direct DDL practice in EAP writing instructional settings in China. Furthermore, the review provides a synthesis of significant discoveries emanating from prior research investigations concerning Chinese university students’ perception of Data-Driven Learning (DDL) and the subsequent impact on their academic writing performance following corpus-based training. Research papers were selected from Scopus-indexed journals and core journals from two main Chinese academic databases (CNKI and Wanfang) published in both English and Chinese over the last ten years based on keyword searches. Results indicated an insufficiency of empirical DDL research despite a noticeable upward trend in corpus research on discourse analysis and indirect corpus applications for material design by language teachers. Research on the direct use of corpora and corpus tools in DDL, particularly in combination with genre-based EAP teaching, remains a relatively small fraction of the whole body of research in Chinese higher education settings. Such scarcity is highly related to the prevailing absence of systematic training in English academic writing registers within most Chinese universities' EAP syllabi due to the Chinese English Medium Instruction policy, where only English major students are mandated to submit English dissertations. Findings also revealed that Chinese learners still held mixed attitudes towards corpus tools influenced by learner differences, limited access to language corpora, and insufficient pre-training on corpus theoretical concepts, despite their improvements in final academic writing performance.

Keywords: corpus linguistics, data-driven learning, EAP, tertiary education in China

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144 Effect of Perioperative Multimodal Analgesia on Postoperative Opioid Consumption and Complications in Elderly Traumatic Hip Fracture Patients: A Systematic Review of Randomised Controlled Trials

Authors: Raheel Shakoor Siddiqui, Shahbaz Malik, Manikandar Srinivas Cheruvu, Sanjay Narayana Murthy, Livio DiMascio

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Background: elderly traumatic hip fracture patients frequently present to trauma services globally. Rising low energy falls amongst an osteoporotic aging population is the commonest cause for injury. Hip fractures in this population are a major cause for severe pain, morbidity and mortality. The term hip fracture is interchangeable with neck of femur fracture, fractured neck of femur or proximal femur fracture. Hip fracture pain management protocols and guidelines suggest conventional analgesia, nerve block and opioid based treatment as rescue analgesia. There is a current global opioid crisis with overuse, abuse and dependence. Adverse opioid related complications in vulnerable elderly patients further adds to morbidity and mortality. Systematic reviews in literature have evidenced superiority of multimodal analgesia in osteoarthritic primary joint replacements compared to opioids however, this has not yet been conducted for elderly traumatic hip fracture patients. Aims: The primary aim of this systematic review is to provide standardised evidence following Cochrane and PRISMA guidance in determining advantages of perioperative multimodal analgesia over conventional opioid based treatments in elderly traumatic hip fractures. Methods: 5 databases were searched from January 2000-2023 which identified 8 randomised controlled trials and 446 total participants. These trials met defined PICOS eligibility criteria of patient mean age ≥ 65 years presenting with a unilateral traumatic fractured neck of femur for operative intervention. Analgesic intervention with perioperative multimodal analgesia has been compared to conventional opioid based analgesia. Outcomes of interest include, primarily, the change in postoperative opioid consumption within a 0-30 postoperative period and secondarily, the change in postoperative adverse events and complications. A qualitative synthesis has been performed due to clinical heterogenicity and variance amongst trials. Results: GRADE evidence of moderate quality supports perioperative multimodal analgesia leads to a reduction in postoperative opioid consumption however, low quality evidence supports a reduction of adverse effects and complications. Conclusion: Perioperative multimodal analgesia whether used preoperative, intraoperative and/or postoperative leads to a reduction in postoperative opioid consumption for elderly traumatic hip fracture patients. This review recommends the use of perioperative multimodal analgesia as part of hip fracture pain protocols however, caution and clinical judgement should be used as the risk of adverse effects may not be lower.

Keywords: trauma, orthopaedics, hip, fracture, neck of femur fracture, analgesia, multimodal analgesia, opioid

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143 A Digital Clone of an Irrigation Network Based on Hardware/Software Simulation

Authors: Pierre-Andre Mudry, Jean Decaix, Jeremy Schmid, Cesar Papilloud, Cecile Munch-Alligne

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In most of the Swiss Alpine regions, the availability of water resources is usually adequate even in times of drought, as evidenced by the 2003 and 2018 summers. Indeed, important natural stocks are for the moment available in the form of snow and ice, but the situation is likely to change in the future due to global and regional climate change. In addition, alpine mountain regions are areas where climate change will be felt very rapidly and with high intensity. For instance, the ice regime of these regions has already been affected in recent years with a modification of the monthly availability and extreme events of precipitations. The current research, focusing on the municipality of Val de Bagnes, located in the canton of Valais, Switzerland, is part of a project led by the Altis company and achieved in collaboration with WSL, BlueArk Entremont, and HES-SO Valais-Wallis. In this region, water occupies a key position notably for winter and summer tourism. Thus, multiple actors want to apprehend the future needs and availabilities of water, on both the 2050 and 2100 horizons, in order to plan the modifications to the water supply and distribution networks. For those changes to be salient and efficient, a good knowledge of the current water distribution networks is of most importance. In the current case, the water drinking network is well documented, but this is not the case for the irrigation one. Since the water consumption for irrigation is ten times higher than for drinking water, data acquisition on the irrigation network is a major point to determine future scenarios. This paper first presents the instrumentation and simulation of the irrigation network using custom-designed IoT devices, which are coupled with a digital clone simulated to reduce the number of measuring locations. The developed IoT ad-hoc devices are energy-autonomous and can measure flows and pressures using industrial sensors such as calorimetric water flow meters. Measurements are periodically transmitted using the LoRaWAN protocol over a dedicated infrastructure deployed in the municipality. The gathered values can then be visualized in real-time on a dashboard, which also provides historical data for analysis. In a second phase, a digital clone of the irrigation network was modeled using EPANET, a software for water distribution systems that performs extended-period simulations of flows and pressures in pressurized networks composed of reservoirs, pipes, junctions, and sinks. As a preliminary work, only a part of the irrigation network was modelled and validated by comparisons with the measurements. The simulations are carried out by imposing the consumption of water at several locations. The validation is performed by comparing the simulated pressures are different nodes with the measured ones. An accuracy of +/- 15% is observed on most of the nodes, which is acceptable for the operator of the network and demonstrates the validity of the approach. Future steps will focus on the deployment of the measurement devices on the whole network and the complete modelling of the network. Then, scenarios of future consumption will be investigated. Acknowledgment— The authors would like to thank the Swiss Federal Office for Environment (FOEN), the Swiss Federal Office for Agriculture (OFAG) for their financial supports, and ALTIS for the technical support, this project being part of the Swiss Pilot program 'Adaptation aux changements climatiques'.

Keywords: hydraulic digital clone, IoT water monitoring, LoRaWAN water measurements, EPANET, irrigation network

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142 The Mitigation of Quercetin on Lead-Induced Neuroinflammation in a Rat Model: Changes in Neuroinflammatory Markers and Memory

Authors: Iliyasu Musa Omoyine, Musa Sunday Abraham, Oladele Sunday Blessing, Iliya Ibrahim Abdullahi, Ibegbu Augustine Oseloka, Nuhu Nana-Hawau, Animoku Abdulrazaq Amoto, Yusuf Abdullateef Onoruoiza, Sambo Sohnap James, Akpulu Steven Peter, Ajayi Abayomi

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The neuroprotective role of inflammation from detrimental intrinsic and extrinsic factors has been reported. However, the overactivation of astrocytes and microglia due to lead toxicity produce excessive pro-inflammatory cytokines, mediating neurodegenerative diseases. The present study investigated the mitigatory effects of quercetin on neuroinflammation, correlating with memory function in lead-exposed rats. In this study, Wistar rats were administered orally with Quercetin (Q: 60 mg/kg) and Succimer as a standard drug (S: 10 mg/kg) for 21 days after lead exposure (Pb: 125 mg/kg) of 21 days or in combination with Pb, once daily for 42 days. Working and reference memory was assessed using an Eight-arm radial water maze (8-ARWM). The changes in brain lead level, the neuronal nitric oxide synthase (nNOS) activity, and the level of neuroinflammatory markers such as tumour necrosis factor-alpha (TNF-α) and Interleukin 1 Beta (IL-1β) were determined. Immunohistochemically, astrocyte expression was evaluated. The results showed that the brain level of lead was increased significantly in lead-exposed rats. The expression of astrocytes increased in the CA3 and CA1 regions of the hippocampus, and the levels of brain TNF-α and IL-1β increased in lead-exposed rats. Lead impaired reference and working memory by increasing reference memory errors and working memory incorrect errors in lead-exposed rats. However, quercetin treatment effectively improved memory and inhibited neuroinflammation by reducing astrocytes’ expression and the levels of TNF-α and IL-1β. The expression of astrocytes and the levels of TNF-α and IL-1β correlated with memory function. The possible explanation for quercetin’s anti-neuroinflammatory effect is that it modulates the activity of cellular proteins involved in the inflammatory response; inhibits the transcription factor of nuclear factor-kappa B (NF-κB), which regulates the expression of proinflammatory molecules; inhibits kinases required for the synthesis of Glial fibrillary acidic protein (GFAP) and modifies the phosphorylation of some proteins, which affect the structure and function of intermediate filament proteins; and, lastly, induces Cyclic-AMP Response Element Binding (CREB) activation and neurogenesis as a compensatory mechanism for memory deficits and neuronal cell death. In conclusion, the levels of neuroinflammatory markers negatively correlated with memory function. Thus, quercetin may be a promising therapy in neuroinflammation and memory dysfunction in populations prone to lead exposure.

Keywords: lead, quercetin, neuroinflammation, memory

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141 Efficacy Testing of a Product in Reducing Facial Hyperpigmentation and Photoaging after a 12-Week Use

Authors: Nalini Kaul, Barrie Drewitt, Elsie Kohoot

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Hyperpigmentation is the third most common pigmentary disorder where dermatologic treatment is sought. It affects all ages resulting in skin darkening because of melanin accumulation. An uneven skin tone because of either exposure to the sun (solar lentigos/age spots/sun spots or skin disruption following acne, or rashes (post-inflammatory hyperpigmentation -PIH) or hormonal changes (melasma) can lead to significant psychosocial impairment. Dyschromia is a result of various alterations in biochemical processes regulating melanogenesis. Treatments include the daily use of sunscreen with lightening, brightening, and exfoliating products. Depigmentation is achieved by various depigmenting agents: common examples are hydroquinone, arbutin, azelaic acid, aloesin, mulberry, licorice extracts, kojic acid, niacinamide, ellagic acid, arbutin, green tea, turmeric, soy, ascorbic acid, and tranexamic acid. These agents affect pigmentation by interfering with mechanisms before, during, and after melanin synthesis. While immediate correction is much sought after, patience and diligence are key. Our objective was to assess the effects of a facial product with pigmentation treatment and UV protection in 35 healthy F (35-65y), meeting the study criteria. Subjects with mild to moderate hyperpigmentation and fine lines with no use of skin-lightening products in the last six months or any dermatological procedures in the last twelve months before the study started were included. Efficacy parameters included expert clinical grading for hyperpigmentation, radiance, skin tone & smoothness, fine lines, and wrinkles bioinstrumentation (Corneometer®, Colorimeter®), digital photography and imaging (Visia-CR®), and self-assessment questionnaires. Safety included grading for erythema, edema, dryness & peeling and self-assessments for itching, stinging, tingling, and burning. Our results showed statistically significant improvement in clinical grading scores, bioinstrumentation, and digital photos for hyperpigmentation-brown spots, fine lines/wrinkles, skin tone, radiance, pores, skin smoothness, and overall appearance compared to baseline. The product was also well-tolerated and liked by subjects. Conclusion: Facial hyperpigmentation is of great concern, and treatment strategies are increasingly sought. Clinical trials with both subjective and objective assessments, imaging analyses, and self-perception are essential to distinguish evidence-based products. The multifunctional cosmetic product tested in this clinical study showed efficacy, tolerability, and subject satisfaction in reducing hyperpigmentation and global photoaging.

Keywords: hyperpigmentation; photoaging, clinical testing, expert visual evaluations, bio-instruments

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140 Immobilization of β-Galactosidase from Kluyveromyces Lactis on Polyethylenimine-Agarose for Production of Lactulose

Authors: Carlos A. C. G. Neto, Natan C. G. Silva, Thais O. Costa, Luciana R. B. Goncalves, Maria v. P. Rocha

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Galactosidases are enzymes responsible for catalyzing lactose hydrolysis reactions and also favoring transgalactosylation reactions for the production of prebiotics, among which lactulose stands out. These enzymes, when immobilized, can have some enzymatic characteristics substantially improved, and the coating of supports with multifunctional polymers in immobilization processes is a promising alternative in order to extend the useful life of the biocatalysts, for example, the coating with polyethyleneimine (PEI). PEI is a flexible polymer that suits the structure of the enzyme, giving greater stability, especially for multimeric enzymes such as β-galactosidases and also protects it from environmental variations, for example, pH and temperature. In addition, it can substantially improve the immobilization parameters and also the efficiency of enzymatic reactions. In this context, the aim of the present work was first to develop biocatalysts of β-galactosidase from Kluyveromyces lactis immobilized on PEI coated agarose, determining the immobilization parameters, its operational and thermal stability, and then to apply it in the hydrolysis of lactose and synthesis of lactulose, using whey as a substrate. This immobilization strategy was chosen in order to improve the catalytic efficiency of the enzyme in the transgalactosylation reaction for the production of prebiotics, and there are few studies with β-galactosidase from this strain. The immobilization of β-galactosidase in agarose previously functionalized with 48% (w/v) glycidol and then coated with 10% (w/v) PEI solution was evaluated using an enzymatic load of 10 mg/g of protein. Subsequently, the hydrolysis and transgalactosylation reactions were conducted at 50 °C, 120 RPM for 20 minutes, using whey (66.7 g/L of lactose) supplemented with 133.3 g/L fructose at a ratio of 1:2 (lactose/fructose). Operational stability studies were performed in the same conditions for 10 cycles. Thermal stabilities of biocatalysts were conducted at 50 ºC in 50 mM phosphate buffer, pH 6.6, with 0.1 mM MnCl2. The biocatalysts whose supports were coated were named AGA_GLY_PEI_GAL, and those that were not coated were named AGA_GLY_GAL. The coating of the support with PEI considerably improved immobilization yield (2.6-fold), the biocatalyst activity (1.4-fold), and efficiency (2.2-fold). The biocatalyst AGA_GLY_PEI_GAL was better than AGA_GLY_GAL in hydrolysis and transgalactosylation reactions, converting 88.92% of lactose at 5 min of reaction and obtaining a residual concentration of 5.24 g/L. Besides that, it was produced 13.90 g/L lactulose in the same time interval. AGA_GLY_PEI_GAL biocatalyst was stable during the 10 cycles evaluated, converting approximately 80% of lactose and producing 10.95 g/L of lactulose even after the tenth cycle. However, the thermal stability of AGA_GLY_GAL biocatalyst was superior, with a half-life time 5 times higher, probably because the enzyme was immobilized by covalent bonding, which is stronger than adsorption (AGA_GLY_PEI_GAL). Therefore, the strategy of coating the supports with PEI has proven to be effective for the immobilization of β-galactosidase from K. lactis, considerably improving the immobilization parameters, as well as the enzyme, catalyzed reactions. In addition, the use of whey as a raw material for lactulose production has proved to be an industrially advantageous alternative.

Keywords: β-galactosidase, immobilization, lactulose, polyethylenimine, whey

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139 Collaborative Management Approach for Logistics Flow Management of Cuban Medicine Supply Chain

Authors: Ana Julia Acevedo Urquiaga, Jose A. Acevedo Suarez, Ana Julia Urquiaga Rodriguez, Neyfe Sablon Cossio

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Despite the progress made in logistics and supply chains fields, it is unavoidable the development of business models that use efficiently information to facilitate the integrated logistics flows management between partners. Collaborative management is an important tool for materializing the cooperation between companies, as a way to achieve the supply chain efficiency and effectiveness. The first face of this research was a comprehensive analysis of the collaborative planning on the Cuban companies. It is evident that they have difficulties in supply chains planning where production, supplies and replenishment planning are independent tasks, as well as logistics and distribution operations. Large inventories generate serious financial and organizational problems for entities, demanding increasing levels of working capital that cannot be financed. Problems were found in the efficient application of Information and Communication Technology on business management. The general objective of this work is to develop a methodology that allows the deployment of a planning and control system in a coordinated way on the medicine’s logistics system in Cuba. To achieve these objectives, several mechanisms of supply chain coordination, mathematical programming models, and other management techniques were analyzed to meet the requirements of collaborative logistics management in Cuba. One of the findings is the practical and theoretical inadequacies of the studied models to solve the current situation of the Cuban logistics systems management. To contribute to the tactical-operative management of logistics, the Collaborative Logistics Flow Management Model (CLFMM) is proposed as a tool for the balance of cycles, capacities, and inventories, always to meet the final customers’ demands in correspondence with the service level expected by these. The CLFMM has as center the supply chain planning and control system as a unique information system, which acts on the processes network. The development of the model is based on the empirical methods of analysis-synthesis and the study cases. Other finding is the demonstration of the use of a single information system to support the supply chain logistics management, allows determining the deadlines and quantities required in each process. This ensures that medications are always available to patients and there are no faults that put the population's health at risk. The simulation of planning and control with the CLFMM in medicines such as dipyrone and chlordiazepoxide, during 5 months of 2017, permitted to take measures to adjust the logistic flow, eliminate delayed processes and avoid shortages of the medicines studied. As a result, the logistics cycle efficiency can be increased to 91%, the inventory rotation would increase, and this results in a release of financial resources.

Keywords: collaborative management, medicine logistic system, supply chain planning, tactical-operative planning

Procedia PDF Downloads 154
138 Iron Doping Enhanced Photocatalytic Nitrogen Fixation Performance of WO₃ with Three-Dimensionally Orderd Macroporous Structure

Authors: Xiaoling Ren, Guidong Yang

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Ammonia, as one of the largest-volume industrial chemicals, is mostly produced by century-old Haber-Bosch process with extreme conditionsand high-cost. Under the circumstance, researchersarededicated in finding new ways to replace the Haber-Bosch process. Photocatalytic nitrogen fixation is a promising sustainable, clear and green strategy for ammonia synthesis, butit is still a big challenge due to the high activation energy for nitrogen. It is essential to develop an efficient photocatalyst for making this approach industrial application. Constructing chemisorption active sites through defect engineering can be defined as an effective and reliable means to improve nitrogen activation by forming the extraordinary coordination environment and electronic structure. Besides, the construction of three-dimensionally orderdmacroporous (3DOM) structured photocatalyst is considered to be one of effectivestrategiesto improve the activity due to it canincrease the diffusion rate of reactants in the interior, which isbeneficial to the mass transfer process of nitrogen molecules in photocatalytic nitrogen reduction. Herein, Fe doped 3DOM WO₃(Fe-3DOM WO₃) without noble metal cocatalysts is synthesized by a polystyrene-template strategy, which is firstly used for photocatalytic nitrogen fixation. To elucidate the chemical nature of the dopant, the X-ray diffraction (XRD) analysiswas conducted. The pure 3DOM WO₃ has a monoclinic type crystal structure. And no additional peak is observed in Fe doped 3DOM WO₃, indicating that the incorporation of Fe atoms did not result in a secondary phase formation. In order to confirm the morphologies of Fe-3DOM WO₃and 3DOM WO₃, scanning electron microscopy (SEM) was employed. The synthesized Fe-3DOM WO₃and 3DOM WO₃ both exhibit a highly ordered three dimensional inverse opal structure with interconnected pores. From high-resolution TEM image of Fe-3DOM WO₃, the ordered lattice fringes with a spacing of 3.84 Å can be assigned to the (001) plane of WO₃, which is consistent with the XRD results. Finally, the photocatalytic nitrogen reduction performance of 3DOM WO₃ and Fe doped 3DOM WO₃with various Fe contents were examined. As a result, both Fe-3DOM WO₃ samples achieve higher ammonia production rate than that of pure 3DOM WO₃, indicating that the doped Fe plays a critical role in the photocatalytic nitrogen fixation performance. To verify the reaction process upon N2 reduction on the Fe-3DOM WO₃, in-situ diffuse reflectance infrared Fourier-transform spectroscopy was employed to monitor the intermediates. The in-situ DRIFTS spectra of Fe-3DOM WO₃ exhibit the increased signals with the irradiation time from 0–60min in the N2 atmosphere. The above results prove that nitrogen is gradually hydrogenated to produce ammonia over Fe-3DOM WO₃. Thiswork would enrich our knowledge in designing efficient photocatalystsfor photocatalytic nitrogen reduction.

Keywords: ammonia, photocatalytic, nitrogen fixation, Fe doped 3DOM WO₃

Procedia PDF Downloads 140
137 Sustainable Production of Pharmaceutical Compounds Using Plant Cell Culture

Authors: David A. Ullisch, Yantree D. Sankar-Thomas, Stefan Wilke, Thomas Selge, Matthias Pump, Thomas Leibold, Kai Schütte, Gilbert Gorr

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Plants have been considered as a source of natural substances for ages. Secondary metabolites from plants are utilized especially in medical applications but are more and more interesting as cosmetical ingredients and in the field of nutraceuticals. However, supply of compounds from natural harvest can be limited by numerous factors i.e. endangered species, low product content, climate impacts and cost intensive extraction. Especially in the pharmaceutical industry the ability to provide sufficient amounts of product and high quality are additional requirements which in some cases are difficult to fulfill by plant harvest. Whereas in many cases the complexity of secondary metabolites precludes chemical synthesis on a reasonable commercial basis, plant cells contain the biosynthetic pathway – a natural chemical factory – for a given compound. A promising approach for the sustainable production of natural products can be plant cell fermentation (PCF®). A thoroughly accomplished development process comprises the identification of a high producing cell line, optimization of growth and production conditions, the development of a robust and reliable production process and its scale-up. In order to address persistent, long lasting production, development of cryopreservation protocols and generation of working cell banks is another important requirement to be considered. So far the most prominent example using a PCF® process is the production of the anticancer compound paclitaxel. To demonstrate the power of plant suspension cultures here we present three case studies: 1) For more than 17 years Phyton produces paclitaxel at industrial scale i.e. up to 75,000 L in scale. With 60 g/kg dw this fully controlled process which is applied according to GMP results in outstanding high yields. 2) Thapsigargin is another anticancer compound which is currently isolated from seeds of Thapsia garganica. Thapsigargin is a powerful cytotoxin – a SERCA inhibitor – and the precursor for the derivative ADT, the key ingredient of the investigational prodrug Mipsagargin (G-202) which is in several clinical trials. Phyton successfully generated plant cell lines capable to express this compound. Here we present data about the screening for high producing cell lines. 3) The third case study covers ingenol-3-mebutate. This compound is found in the milky sap of the intact plants of the Euphorbiacae family at very low concentrations. Ingenol-3-mebutate is used in Picato® which is approved against actinic keratosis. Generation of cell lines expressing significant amounts of ingenol-3-mebutate is another example underlining the strength of plant cell culture. The authors gratefully acknowledge Inspyr Therapeutics for funding.

Keywords: Ingenol-3-mebutate, plant cell culture, sustainability, thapsigargin

Procedia PDF Downloads 218
136 Urban Open Source: Synthesis of a Citizen-Centric Framework to Design Densifying Cities

Authors: Shaurya Chauhan, Sagar Gupta

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Prominent urbanizing centres across the globe like Delhi, Dhaka, or Manila have exhibited that development often faces a challenge in bridging the gap among the top-down collective requirements of the city and the bottom-up individual aspirations of the ever-diversifying population. When this exclusion is intertwined with rapid urbanization and diversifying urban demography: unplanned sprawl, poor planning, and low-density development emerge as automated responses. In parallel, new ideas and methods of densification and public participation are being widely adopted as sustainable alternatives for the future of urban development. This research advocates a collaborative design method for future development: one that allows rapid application with its prototypical nature and an inclusive approach with mediation between the 'user' and the 'urban', purely with the use of empirical tools. Building upon the concepts and principles of 'open-sourcing' in design, the research establishes a design framework that serves the current user requirements while allowing for future citizen-driven modifications. This is synthesized as a 3-tiered model: user needs – design ideology – adaptive details. The research culminates into a context-responsive 'open source project development framework' (hereinafter, referred to as OSPDF) that can be used for on-ground field applications. To bring forward specifics, the research looks at a 300-acre redevelopment in the core of a rapidly urbanizing city as a case encompassing extreme physical, demographic, and economic diversity. The suggestive measures also integrate the region’s cultural identity and social character with the diverse citizen aspirations, using architecture and urban design tools, and references from recognized literature. This framework, based on a vision – feedback – execution loop, is used for hypothetical development at the five prevalent scales in design: master planning, urban design, architecture, tectonics, and modularity, in a chronological manner. At each of these scales, the possible approaches and avenues for open- sourcing are identified and validated, through hit-and-trial, and subsequently recorded. The research attempts to re-calibrate the architectural design process and make it more responsive and people-centric. Analytical tools such as Space, Event, and Movement by Bernard Tschumi and Five-Point Mental Map by Kevin Lynch, among others, are deep rooted in the research process. Over the five-part OSPDF, a two-part subsidiary process is also suggested after each cycle of application, for a continued appraisal and refinement of the framework and urban fabric with time. The research is an exploration – of the possibilities for an architect – to adopt the new role of a 'mediator' in development of the contemporary urbanity.

Keywords: open source, public participation, urbanization, urban development

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135 Nonconventional Method for Separation of Rosmarinic Acid: Synergic Extraction

Authors: Lenuta Kloetzer, Alexandra C. Blaga, Dan Cascaval, Alexandra Tucaliuc, Anca I. Galaction

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Rosmarinic acid, an ester of caffeic acid and 3-(3,4-dihydroxyphenyl) lactic acid, is considered a valuable compound for the pharmaceutical and cosmetic industries due to its antimicrobial, antioxidant, antiviral, anti-allergic, and anti-inflammatory effects. It can be obtained by extraction from vegetable or animal materials, by chemical synthesis and biosynthesis. Indifferent of the method used for rosmarinic acid production, the separation and purification process implies high amount of raw materials and laborious stages leading to high cost for and limitations of the separation technology. This study focused on separation of rosmarinic acid by synergic reactive extraction with a mixture of two extractants, one acidic (acid di-(2ethylhexyl) phosphoric acid, D2EHPA) and one with basic character (Amberlite LA-2). The studies were performed in experimental equipment consisting of an extraction column where the phases’ mixing was made by mean of a perforated disk with 45 mm diameter and 20% free section, maintained at the initial contact interface between the aqueous and organic phases. The vibrations had a frequency of 50 s⁻¹ and 5 mm amplitude. The extraction was carried out in two solvents with different dielectric constants (n-heptane and dichloromethane) in which the extractants mixture of varying concentration was dissolved. The pH-value of initial aqueous solution was varied between 1 and 7. The efficiency of the studied extraction systems was quantified by distribution and synergic coefficients. For calculating these parameters, the rosmarinic acid concentration in the initial aqueous solution and in the raffinate have been measured by HPLC. The influences of extractants concentrations and solvent polarity on the efficiency of rosmarinic acid separation by synergic extraction with a mixture of Amberlite LA-2 and D2EHPA have been analyzed. In the reactive extraction system with a constant concentration of Amberlite LA-2 in the organic phase, the increase of D2EHPA concentration leads to decrease of the synergic coefficient. This is because the increase of D2EHPA concentration prevents the formation of amine adducts and, consequently, affects the hydrophobicity of the interfacial complex with rosmarinic acid. For these reasons, the diminution of synergic coefficient is more important for dichloromethane. By maintaining a constant value of D2EHPA concentration and increasing the concentration of Amberlite LA-2, the synergic coefficient could become higher than 1, its highest values being reached for n-heptane. Depending on the solvent polarity and D2EHPA amount in the solvent phase, the synergic effect is observed for Amberlite LA-2 concentrations over 20 g/l dissolved in n-heptane. Thus, by increasing the concentration of D2EHPA from 5 to 40 g/l, the minimum concentration value of Amberlite LA-2 corresponding to synergism increases from 20 to 40 g/l for the solvent with lower polarity, namely, n-heptane, while there is no synergic effect recorded for dichloromethane. By analysing the influences of the main factors (organic phase polarity, extractant concentration in the mixture) on the efficiency of synergic extraction of rosmarinic acid, the most important synergic effect was found to correspond to the extractants mixture containing 5 g/l D2EHPA and 40 g/l Amberlite LA-2 dissolved in n-heptane.

Keywords: Amberlite LA-2, di(2-ethylhexyl) phosphoric acid, rosmarinic acid, synergic effect

Procedia PDF Downloads 262
134 Integrating Multiple Types of Value in Natural Capital Accounting Systems: Environmental Value Functions

Authors: Pirta Palola, Richard Bailey, Lisa Wedding

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Societies and economies worldwide fundamentally depend on natural capital. Alarmingly, natural capital assets are quickly depreciating, posing an existential challenge for humanity. The development of robust natural capital accounting systems is essential for transitioning towards sustainable economic systems and ensuring sound management of capital assets. However, the accurate, equitable and comprehensive estimation of natural capital asset stocks and their accounting values still faces multiple challenges. In particular, the representation of socio-cultural values held by groups or communities has arguably been limited, as to date, the valuation of natural capital assets has primarily been based on monetary valuation methods and assumptions of individual rationality. People relate to and value the natural environment in multiple ways, and no single valuation method can provide a sufficiently comprehensive image of the range of values associated with the environment. Indeed, calls have been made to improve the representation of multiple types of value (instrumental, intrinsic, and relational) and diverse ontological and epistemological perspectives in environmental valuation. This study addresses this need by establishing a novel valuation framework, Environmental Value Functions (EVF), that allows for the integration of multiple types of value in natural capital accounting systems. The EVF framework is based on the estimation and application of value functions, each of which describes the relationship between the value and quantity (or quality) of an ecosystem component of interest. In this framework, values are estimated in terms of change relative to the current level instead of calculating absolute values. Furthermore, EVF was developed to also support non-marginalist conceptualizations of value: it is likely that some environmental values cannot be conceptualized in terms of marginal changes. For example, ecological resilience value may, in some cases, be best understood as a binary: it either exists (1) or is lost (0). In such cases, a logistic value function may be used as the discriminator. Uncertainty in the value function parameterization can be considered through, for example, Monte Carlo sampling analysis. The use of EVF is illustrated with two conceptual examples. For the first time, EVF offers a clear framework and concrete methodology for the representation of multiple types of value in natural capital accounting systems, simultaneously enabling 1) the complementary use and integration of multiple valuation methods (monetary and non-monetary); 2) the synthesis of information from diverse knowledge systems; 3) the recognition of value incommensurability; 4) marginalist and non-marginalist value analysis. Furthermore, with this advancement, the coupling of EVF and ecosystem modeling can offer novel insights to the study of spatial-temporal dynamics in natural capital asset values. For example, value time series can be produced, allowing for the prediction and analysis of volatility, long-term trends, and temporal trade-offs. This approach can provide essential information to help guide the transition to a sustainable economy.

Keywords: economics of biodiversity, environmental valuation, natural capital, value function

Procedia PDF Downloads 159
133 Traumatic Brain Injury Induced Lipid Profiling of Lipids in Mice Serum Using UHPLC-Q-TOF-MS

Authors: Seema Dhariwal, Kiran Maan, Ruchi Baghel, Apoorva Sharma, Poonam Rana

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Introduction: Traumatic brain injury (TBI) is defined as the temporary or permanent alteration in brain function and pathology caused by an external mechanical force. It represents the leading cause of mortality and morbidity among children and youth individuals. Various models of TBI in rodents have been developed in the laboratory to mimic the scenario of injury. Blast overpressure injury is common among civilians and military personnel, followed by accidents or explosive devices. In addition to this, the lateral Controlled cortical impact (CCI) model mimics the blunt, penetrating injury. Method: In the present study, we have developed two different mild TBI models using blast and CCI injury. In the blast model, helium gas was used to create an overpressure of 130 kPa (±5) via a shock tube, and CCI injury was induced with an impact depth of 1.5mm to create diffusive and focal injury, respectively. C57BL/6J male mice (10-12 weeks) were divided into three groups: (1) control, (2) Blast treated, (3) CCI treated, and were exposed to different injury models. Serum was collected on Day1 and day7, followed by biphasic extraction using MTBE/Methanol/Water. Prepared samples were separated on Charged Surface Hybrid (CSH) C18 column and acquired on UHPLC-Q-TOF-MS using ESI probe with inhouse optimized parameters and method. MS peak list was generated using Markerview TM. Data were normalized, Pareto-scaled, and log-transformed, followed by multivariate and univariate analysis in metaboanalyst. Result and discussion: Untargeted profiling of lipids generated extensive data features, which were annotated through LIPID MAPS® based on their m/z and were further confirmed based on their fragment pattern by LipidBlast. There is the final annotation of 269 features in the positive and 182 features in the negative mode of ionization. PCA and PLS-DA score plots showed clear segregation of injury groups to controls. Among various lipids in mild blast and CCI, five lipids (Glycerophospholipids {PC 30:2, PE O-33:3, PG 28:3;O3 and PS 36:1 } and fatty acyl { FA 21:3;O2}) were significantly altered in both injury groups at Day 1 and Day 7, and also had VIP score >1. Pathway analysis by Biopan has also shown hampered synthesis of Glycerolipids and Glycerophospholipiods, which coincides with earlier reports. It could be a direct result of alteration in the Acetylcholine signaling pathway in response to TBI. Understanding the role of a specific class of lipid metabolism, regulation and transport could be beneficial to TBI research since it could provide new targets and determine the best therapeutic intervention. This study demonstrates the potential lipid biomarkers which can be used for injury severity diagnosis and identification irrespective of injury type (diffusive or focal).

Keywords: LipidBlast, lipidomic biomarker, LIPID MAPS®, TBI

Procedia PDF Downloads 90
132 Conceptualization and Assessment of Key Competencies for Children in Preschools: A Case Study in Southwest China

Authors: Yumei Han, Naiqing Song, Xiaoping Yang, Yuping Han

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This study explores the conceptualization of key competencies that children are expected to develop in three year preschools (age 3-6) and the assessment practices of such key competencies in China. Assessment of children development has been put into the central place of early childhood education quality evaluation system in China. In the context of students key competencies development centered education reform in China, defining and selecting key competencies of children in preschools are of great significance in that they would lay a solid foundation for children’s lifelong learning path, and they would lead to curriculum and instruction reform, teacher development reform as well as quality evaluation reform in the early childhood education area. Based on sense making theory and framework, this study adopted multiple stakeholders’ (early childhood educators, parents, evaluation administrators, scholars in the early childhood education field) perspectives and grass root voices to conceptualize and operationalize key competencies for children in preschools in Southwest China. On the ground of children development theories, Chinese and international literature related to children development and key competencies, and key competencies frameworks by UNESCO, OECD and other nations, the authors designed a two-phase sequential mixed method study to address three main questions: (a) How is early childhood key competency defined or labeled from literature and from different stakeholders’ views? (b) Based on the definitions explicated in the literature and the surveys on different stakeholders, what domains and components are regarded to constitute the key competency framework of children in three-year preschools in China? (c) How have early childhood key competencies been assessed and measured, and how such assessment and measurement contribute to enhancing early childhood development quality? On the first phase, a series of focus group surveys were conducted among different types of stakeholders around the research questions. Moreover, on the second phase, based on the coding of the participants’ answers, together with literature synthesis findings, a questionnaire survey was designed and conducted to select most commonly expected components of preschool children’s key competencies. Semi-structured open questions were also included in the questionnaire for the participants to add on competencies beyond the checklist. Rudimentary findings show agreeable concerns on the significance and necessity of conceptualization and assessment of key competencies for children in preschools, and a key competencies framework composed of 7 domains and 25 indicators was constructed. Meanwhile, the findings also show issues in the current assessment practices of children’s competencies, such as lack of effective assessment tools, lack of teacher capacity in applying the tools to evaluating children and advancing children development accordingly. Finally, the authors put forth suggestions and implications for China and international communities in terms of restructuring early childhood key competencies framework, and promoting child development centered reform in early childhood education quality evaluation and development.

Keywords: assessment, conceptualization, early childhood education quality in China, key competencies

Procedia PDF Downloads 224
131 Zeolite 4A-confined Ni-Co Nanocluster: An Efficient and Durable Electrocatalyst for Alkaline Methanol Oxidation Reaction

Authors: Sarmistha Baruah, Akshai Kumar, Nageswara Rao Peela

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The global energy crisis due to the dependence on fossil fuels and its limited reserves as well as environmental pollution are key concerns to the research communities. However, the implementation of alcohol-based fuel cells such as methanol is anticipated as a reliable source of future energy technology due to their high energy density, environment friendliness, ease of storage, transportation, etc. To drive the anodic methanol oxidation reaction (MOR) in direct methanol fuel cells (DMFCs), an active and long-lasting catalyst is necessary for efficient energy conversion from methanol. Recently, transition metal-zeolite-based materials have been considered versatile catalysts for a variety of industrial and lab-scale processes. Large specific surface area, well-organized micropores, and adjustable acidity/basicity are characteristics of zeolites that make them excellent supports for immobilizing small-sized and highly dispersed metal species. Significant advancement in the production and characterization of well-defined metal clusters encapsulated within zeolite matrix has substantially expanded the library of materials available, and consequently, their catalytic efficacy. In this context, we developed bimetallic Ni-Co catalysts encapsulated within LTA (also known as 4A) zeolite via a method combined with the in-situ encapsulation of metal species using hydrothermal treatment followed by a chemical reduction process. The prepared catalyst was characterized using advanced characterization techniques, such as X-ray diffraction (XRD), field emission transmission electron microscope (FETEM), field emission scanning electron microscope (FESEM), energy dispersive X-ray (EDX), and X-ray photoelectron spectroscopy (XPS). The electrocatalytic activity of the catalyst for MOR was carried out in an alkaline medium at room temperature using techniques such as cyclic voltammetry (CV), and chronoamperometry (CA). The resulting catalyst exhibited better catalytic activity of 12.1 mA cm-2 at 1.12 V vs Ag/AgCl and retained remarkable stability (~77%) even after 1000 cycles CV test for the electro-oxidation of methanol in alkaline media without any significant microstructural changes. The high surface area, better Ni-Co species integration in the zeolite, and the ample amount of surface hydroxyl groups contribute to highly dispersed active sites and quick analyte diffusion, which provide notable MOR kinetics. Thus, this study will open up new possibilities to develop a noble metal-free zeolite-based electrocatalyst due to its simple synthesis steps, large-scale fabrication, improved stability, and efficient activity for DMFC application.

Keywords: alkaline media, bimetallic, encapsulation, methanol oxidation reaction, LTA zeolite.

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130 Switchable Lipids: From a Molecular Switch to a pH-Sensitive System for the Drug and Gene Delivery

Authors: Jeanne Leblond, Warren Viricel, Amira Mbarek

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Although several products have reached the market, gene therapeutics are still in their first stages and require optimization. It is possible to improve their lacking efficiency by the use of carefully engineered vectors, able to carry the genetic material through each of the biological barriers they need to cross. In particular, getting inside the cell is a major challenge, because these hydrophilic nucleic acids have to cross the lipid-rich plasmatic and/or endosomal membrane, before being degraded into lysosomes. It takes less than one hour for newly endocytosed liposomes to reach highly acidic lysosomes, meaning that the degradation of the carried gene occurs rapidly, thus limiting the transfection efficiency. We propose to use a new pH-sensitive lipid able to change its conformation upon protonation at endosomal pH values, leading to the disruption of the lipidic bilayer and thus to the fast release of the nucleic acids into the cytosol. It is expected that this new pH-sensitive mechanism promote endosomal escape of the gene, thereby its transfection efficiency. The main challenge of this work was to design a preparation presenting fast-responding lipidic bilayer destabilization properties at endosomal pH 5 while remaining stable at blood pH value and during storage. A series of pH-sensitive lipids able to perform a conformational switch upon acidification were designed and synthesized. Liposomes containing these switchable lipids, as well as co-lipids were prepared and characterized. The liposomes were stable at 4°C and pH 7.4 for several months. Incubation with siRNA led to the full entrapment of nucleic acids as soon as the positive/negative charge ratio was superior to 2. The best liposomal formulation demonstrated a silencing efficiency up to 10% on HeLa cells, very similar to a commercial agent, with a lowest toxicity than the commercial agent. Using flow cytometry and microscopy assays, we demonstrated that drop of pH was required for the transfection efficiency, since bafilomycin blocked the transfection efficiency. Additional evidence was brought by the synthesis of a negative control lipid, which was unable to switch its conformation, and consequently exhibited no transfection ability. Mechanistic studies revealed that the uptake was mediated through endocytosis, by clathrin and caveolae pathways, as reported for previous lipid nanoparticle systems. This potent system was used for the treatment of hypercholesterolemia. The switchable lipids were able to knockdown PCSK9 expression on human hepatocytes (Huh-7). Its efficiency is currently evaluated on in vivo mice model of PCSK9 KO mice. In summary, we designed and optimized a new cationic pH-sensitive lipid for gene delivery. Its transfection efficiency is similar to the best available commercial agent, without the usually associated toxicity. The promising results lead to its use for the treatment of hypercholesterolemia on a mice model. Anticancer applications and pulmonary chronic disease are also currently investigated.

Keywords: liposomes, siRNA, pH-sensitive, molecular switch

Procedia PDF Downloads 184
129 Comparison of GIS-Based Soil Erosion Susceptibility Models Using Support Vector Machine, Binary Logistic Regression and Artificial Neural Network in the Southwest Amazon Region

Authors: Elaine Lima Da Fonseca, Eliomar Pereira Da Silva Filho

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The modeling of areas susceptible to soil loss by hydro erosive processes consists of a simplified instrument of reality with the purpose of predicting future behaviors from the observation and interaction of a set of geoenvironmental factors. The models of potential areas for soil loss will be obtained through binary logistic regression, artificial neural networks, and support vector machines. The choice of the municipality of Colorado do Oeste in the south of the western Amazon is due to soil degradation due to anthropogenic activities, such as agriculture, road construction, overgrazing, deforestation, and environmental and socioeconomic configurations. Initially, a soil erosion inventory map constructed through various field investigations will be designed, including the use of remotely piloted aircraft, orbital imagery, and the PLANAFLORO/RO database. 100 sampling units with the presence of erosion will be selected based on the assumptions indicated in the literature, and, to complement the dichotomous analysis, 100 units with no erosion will be randomly designated. The next step will be the selection of the predictive parameters that exert, jointly, directly, or indirectly, some influence on the mechanism of occurrence of soil erosion events. The chosen predictors are altitude, declivity, aspect or orientation of the slope, curvature of the slope, composite topographic index, flow power index, lineament density, normalized difference vegetation index, drainage density, lithology, soil type, erosivity, and ground surface temperature. After evaluating the relative contribution of each predictor variable, the erosion susceptibility model will be applied to the municipality of Colorado do Oeste - Rondônia through the SPSS Statistic 26 software. Evaluation of the model will occur through the determination of the values of the R² of Cox & Snell and the R² of Nagelkerke, Hosmer and Lemeshow Test, Log Likelihood Value, and Wald Test, in addition to analysis of the Confounding Matrix, ROC Curve and Accumulated Gain according to the model specification. The validation of the synthesis map resulting from both models of the potential risk of soil erosion will occur by means of Kappa indices, accuracy, and sensitivity, as well as by field verification of the classes of susceptibility to erosion using drone photogrammetry. Thus, it is expected to obtain the mapping of the following classes of susceptibility to erosion very low, low, moderate, very high, and high, which may constitute a screening tool to identify areas where more detailed investigations need to be carried out, applying more efficient social resources.

Keywords: modeling, susceptibility to erosion, artificial intelligence, Amazon

Procedia PDF Downloads 41
128 The Practise of Hand Drawing as a Premier Form of Representation in Architectural Design Teaching: The Case of FAUP

Authors: Rafael Santos, Clara Pimenta Do Vale, Barbara Bogoni, Poul Henning Kirkegaard

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In the last decades, the relevance of hand drawing has decreased in the scope of architectural education. However, some schools continue to recognize its decisive role, not only in the architectural design teaching, but in the whole of architectural training. With this paper it is intended to present the results of a research developed on the following problem: the practise of hand drawing as a premier form of representation in architectural design teaching. The research had as its object the educational model of the Faculty of Architecture of the University of Porto (FAUP) and was led by three main objectives: to identify the circumstance that promoted hand drawing as a form of representation in FAUP's model; to characterize the types of hand drawing and their role in that model; to determine the particularities of hand drawing as a premier form of representation in architectural design teaching. Methodologically, the research was conducted according to a qualitative embedded single-case study design. The object – i.e., the educational model – was approached in FAUP case considering its Context and three embedded unities of analysis: the educational Purposes, Principles and Practices. In order to guide the procedures of data collection and analysis, a Matrix for the Characterization (MCC) was developed. As a methodological tool, the MCC allowed to relate the three embedded unities of analysis with the three main sources of evidence where the object manifests itself: the professors, expressing how the model is Assumed; the architectural design classes, expressing how the model is Achieved; and the students, expressing how the model is Acquired. The main research methods used were the naturalistic and participatory observation, in-person-interview and documentary and bibliographic review. The results reveal that the educational model of FAUP – following the model of the former Porto School – was largely due to the methodological foundations created with the hand drawing teaching-learning processes. In the absence of a culture of explicit theoretical elaboration or systematic research, hand drawing was the support for the continuity of the school, an expression of a unified thought about what should be the reflection and practice of architecture. As a form of representation, hand drawing plays a transversal role in the entire educational model, since its purposes are not limited to the conception of architectural design – it is also a means for perception, analysis and synthesis. Regarding the architectural design teaching, there seems to be an understanding of three complementary dimensions of didactics: the instrumental, methodological and propositional dimension. At FAUP, hand drawing is recognized as the common denominator among these dimensions, according to the idea of "globality of drawing". It is expected that the knowledge base developed in this research may have three main contributions: to contribute to the maintenance and valorisation of FAUP’s model; through the precise description of the methodological procedures, to contribute by transferability to similar studies; through the critical and objective framework of the problem underlying the hand drawing in architectural design teaching, to contribute to the broader discussion concerning the contemporary challenges on architectural education.

Keywords: architectural design teaching, architectural education, forms of representation, hand drawing

Procedia PDF Downloads 97
127 Rotterdam in Transition: A Design Case for a Low-Carbon Transport Node in Lombardijen

Authors: Halina Veloso e Zarate, Manuela Triggianese

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The urban challenges posed by rapid population growth, climate adaptation, and sustainable living have compelled Dutch cities to reimagine their built environment and transportation systems. As a pivotal contributor to CO₂ emissions, the transportation sector in the Netherlands demands innovative solutions for transitioning to low-carbon mobility. This study investigates the potential of transit oriented development (TOD) as a strategy for achieving carbon reduction and sustainable urban transformation. Focusing on the Lombardijen station area in Rotterdam, which is targeted for significant densification, this paper presents a design-oriented exploration of a low-carbon transport node. By employing a research-by-design methodology, this study delves into multifaceted factors and scales, aiming to propose future scenarios for Lombardijen. Drawing from a synthesis of existing literature, applied research, and practical insights, a robust design framework emerges. To inform this framework, governmental data concerning the built environment and material embodied carbon are harnessed. However, the restricted access to crucial datasets, such as property ownership information from the cadastre and embodied carbon data from De Nationale Milieudatabase, underscores the need for improved data accessibility, especially during the concept design phase. The findings of this research contribute fundamental insights not only to the Lombardijen case but also to TOD studies across Rotterdam's 13 nodes and similar global contexts. Spatial data related to property ownership facilitated the identification of potential densification sites, underscoring its importance for informed urban design decisions. Additionally, the paper highlights the disparity between the essential role of embodied carbon data in environmental assessments for building permits and its limited accessibility due to proprietary barriers. Although this study lays the groundwork for sustainable urbanization through TOD-based design, it acknowledges an area of future research worthy of exploration: the socio-economic dimension. Given the complex socio-economic challenges inherent in the Lombardijen area, extending beyond spatial constraints, a comprehensive approach demands integration of mobility infrastructure expansion, land-use diversification, programmatic enhancements, and climate adaptation. While the paper adopts a TOD lens, it refrains from an in-depth examination of issues concerning equity and inclusivity, opening doors for subsequent research to address these aspects crucial for holistic urban development.

Keywords: Rotterdam zuid, transport oriented development, carbon emissions, low-carbon design, cross-scale design, data-supported design

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126 Composition and Catalytic Behaviour of Biogenic Iron Containing Materials Obtained by Leptothrix Bacteria Cultivation in Different Growth Media

Authors: M. Shopska, D. Paneva, G. Kadinov, Z. Cherkezova-Zheleva, I. Mitov

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The iron containing materials are used as catalysts in different processes. The chemical methods of their synthesis use toxic and expensive chemicals; sophisticated devices; energy consumption processes that raise their cost. Besides, dangerous waste products are formed. At present time such syntheses are out of date and wasteless technologies are indispensable. The bioinspired technologies are consistent with the ecological requirements. Different microorganisms participate in the biomineralization of the iron and some phytochemicals are involved, too. The methods for biogenic production of iron containing materials are clean, simple, nontoxic, realized at ambient temperature and pressure, cheaper. The biogenic iron materials embrace different iron compounds. Due to their origin these substances are nanosized, amorphous or poorly crystalline, porous and have number of useful properties like SPM, high magnetism, low toxicity, biocompatibility, absorption of microwaves, high surface area/volume ratio, active sites on the surface with unusual coordination that distinguish them from the bulk materials. The biogenic iron materials are applied in the heterogeneous catalysis in different roles - precursor, active component, support, immobilizer. The application of biogenic iron oxide materials gives rise to increased catalytic activity in comparison with those of abiotic origin. In our study we investigated the catalytic behavior of biomasses obtained by cultivation of Leptothrix bacteria in three nutrition media – Adler, Fedorov, and Lieske. The biomass composition was studied by Moessbauer spectroscopy and transmission IRS. Catalytic experiments on CO oxidation were carried out using in situ DRIFTS. Our results showed that: i) the used biomasses contain α-FeOOH, γ-FeOOH, γ-Fe2O3 in different ratios; ii) the biomass formed in Adler medium contains γ-FeOOH as main phase. The CO conversion was about 50% as evaluated by decreased integrated band intensity in the gas mixture spectra during the reaction. The main phase in the spent sample is γ-Fe2O3; iii) the biomass formed in Lieske medium contains α-FeOOH. The CO conversion was about 20%. The main phase in the spent sample is α-Fe2O3; iv) the biomass formed in Fedorov medium contains γ-Fe2O3 as main phase. CO conversion in the test reaction was about 19%. The results showed that the catalytic activity up to 200°C resulted predominantly from α-FeOOH and γ-FeOOH. The catalytic activity at temperatures higher than 200°C was due to the formation of γ-Fe2O3. The oxyhydroxides, which are the principal compounds in the biomass, have low catalytic activity in the used reaction; the maghemite has relatively good catalytic activity; the hematite has activity commensurate with that of the oxyhydroxides. Moreover it can be affirmed that catalytic activity is inherent in maghemite, which is obtained by transformation of the biogenic lepidocrocite, i.e. it has biogenic precursor.

Keywords: nanosized biogenic iron compounds, catalytic behavior in reaction of CO oxidation, in situ DRIFTS, Moessbauer spectroscopy

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125 ENDO-β-1,4-Xylanase from Thermophilic Geobacillus stearothermophilus: Immobilization Using Matrix Entrapment Technique to Increase the Stability and Recycling Efficiency

Authors: Afsheen Aman, Zainab Bibi, Shah Ali Ul Qader

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Introduction: Xylan is a heteropolysaccharide composed of xylose monomers linked together through 1,4 linkages within a complex xylan network. Owing to wide applications of xylan hydrolytic products (xylose, xylobiose and xylooligosaccharide) the researchers are focusing towards the development of various strategies for efficient xylan degradation. One of the most important strategies focused is the use of heat tolerant biocatalysts which acts as strong and specific cleaving agents. Therefore, the exploration of microbial pool from extremely diversified ecosystem is considerably vital. Microbial populations from extreme habitats are keenly explored for the isolation of thermophilic entities. These thermozymes usually demonstrate fast hydrolytic rate, can produce high yields of product and are less prone to microbial contamination. Another possibility of degrading xylan continuously is the use of immobilization technique. The current work is an effort to merge both the positive aspects of thermozyme and immobilization technique. Methodology: Geobacillus stearothermophilus was isolated from soil sample collected near the blast furnace site. This thermophile is capable of producing thermostable endo-β-1,4-xylanase which cleaves xylan effectively. In the current study, this thermozyme was immobilized within a synthetic and a non-synthetic matrice for continuous production of metabolites using entrapment technique. The kinetic parameters of the free and immobilized enzyme were studied. For this purpose calcium alginate and polyacrylamide beads were prepared. Results: For the synthesis of immobilized beads, sodium alginate (40.0 gL-1) and calcium chloride (0.4 M) was used amalgamated. The temperature (50°C) and pH (7.0) optima of immobilized enzyme remained same for xylan hydrolysis however, the enzyme-substrate catalytic reaction time raised from 5.0 to 30.0 minutes as compared to free counterpart. Diffusion limit of high molecular weight xylan (corncob) caused a decline in Vmax of immobilized enzyme from 4773 to 203.7 U min-1 whereas, Km value increased from 0.5074 to 0.5722 mg ml-1 with reference to free enzyme. Immobilized endo-β-1,4-xylanase showed its stability at high temperatures as compared to free enzyme. It retained 18% and 9% residual activity at 70°C and 80°C, respectively whereas; free enzyme completely lost its activity at both temperatures. The Immobilized thermozyme displayed sufficient recycling efficiency and can be reused up to five reaction cycles, indicating that this enzyme can be a plausible candidate in paper processing industry. Conclusion: This thermozyme showed better immobilization yield and operational stability with the purpose of hydrolyzing the high molecular weight xylan. However, the enzyme immobilization properties can be improved further by immobilizing it on different supports for industrial purpose.

Keywords: immobilization, reusability, thermozymes, xylanase

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124 MOF [(4,4-Bipyridine)₂(O₂CCH₃)₂Zn]N as Heterogeneous Acid Catalysts for the Transesterification of Canola Oil

Authors: H. Arceo, S. Rincon, C. Ben-Youssef, J. Rivera, A. Zepeda

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Biodiesel has emerged as a material with great potential as a renewable energy replacement to current petroleum-based diesel. Recently, biodiesel production is focused on the development of more efficient, sustainable process with lower costs of production. In this sense, a “green” approach to biodiesel production has stimulated the use of sustainable heterogeneous acid catalysts, that are better alternatives to conventional processes because of their simplicity and the simultaneous promotion of esterification and transesterification reactions from low-grade, highly-acidic and water containing oils without the formation of soap. The focus of this methodology is the development of new heterogeneous catalysts that under ordinary reaction conditions could reach yields similar to homogeneous catalysis. In recent years, metal organic frameworks (MOF) have attracted much interest for their potential as heterogeneous acid catalysts. They are crystalline porous solids formed by association of transition metal ions or metal–oxo clusters and polydentate organic ligands. This hybridization confers MOFs unique features such as high thermal stability, larger pore size, high specific area, high selectivity and recycling potential. Thus, MOF application could be a way to improve the biodiesel production processes. In this work, we evaluated the catalytic activity of MOF [(4,4-bipyridine)2(O₂CCH₃)2Zn]n (MOF Zn-I) for the synthesis of biodiesel from canola oil. The reaction conditions were optimized using the response surface methodology with a compound design central with 24. The variables studied were: Reaction temperature, amount of catalyst, molar ratio oil: MetOH and reaction time. The preparation MOF Zn-I was performed by mixing 5 mmol 4´4 dipyridine dissolved in 25 mL methanol with 10 mmol Zn(O₂CCH₃)₂ ∙ 2H₂O in 25 mL water. The crystals were obtained by slow evaporation of the solvents at 60°C for 18 h. The prepared catalyst was characterized using X-ray diffraction (XRD) and Fourier transform infrared spectrometer (FT-IR). The prepared catalyst was characterized using X-ray diffraction (XRD) and Fourier transform infrared spectrometer (FT-IR). Experiments were performed using commercially available canola oil in ace pressure tube under continuous stirring. The reaction was filtered and vacuum distilled to remove the catalyst and excess alcohol, after which it was centrifuged to separate the obtained biodiesel and glycerol. 1H NMR was used to calculate the process yield. GC-MS was used to quantify the fatty acid methyl ester (FAME). The results of this study show that the acid catalyst MOF Zn-I could be used as catalyst for biodiesel production through heterogeneous transesterification of canola oil with FAME yield 82 %. The optimum operating condition for the catalytic reaction were of 142°C, 0.5% catalyst/oil weight ratio, 1:30 oil:MeOH molar ratio and 5 h reaction time.

Keywords: fatty acid methyl ester, heterogeneous acid catalyst, metal organic framework, transesterification

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

Authors: Ankur Chaudhuri, Sibani Sen Chakraborty

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

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

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122 Linguistic Cyberbullying, a Legislative Approach

Authors: Simona Maria Ignat

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Bullying online has been an increasing studied topic during the last years. Different approaches, psychological, linguistic, or computational, have been applied. To our best knowledge, a definition and a set of characteristics of phenomenon agreed internationally as a common framework are still waiting for answers. Thus, the objectives of this paper are the identification of bullying utterances on Twitter and their algorithms. This research paper is focused on the identification of words or groups of words, categorized as “utterances”, with bullying effect, from Twitter platform, extracted on a set of legislative criteria. This set is the result of analysis followed by synthesis of law documents on bullying(online) from United States of America, European Union, and Ireland. The outcome is a linguistic corpus with approximatively 10,000 entries. The methods applied to the first objective have been the following. The discourse analysis has been applied in identification of keywords with bullying effect in texts from Google search engine, Images link. Transcription and anonymization have been applied on texts grouped in CL1 (Corpus linguistics 1). The keywords search method and the legislative criteria have been used for identifying bullying utterances from Twitter. The texts with at least 30 representations on Twitter have been grouped. They form the second corpus linguistics, Bullying utterances from Twitter (CL2). The entries have been identified by using the legislative criteria on the the BoW method principle. The BoW is a method of extracting words or group of words with same meaning in any context. The methods applied for reaching the second objective is the conversion of parts of speech to alphabetical and numerical symbols and writing the bullying utterances as algorithms. The converted form of parts of speech has been chosen on the criterion of relevance within bullying message. The inductive reasoning approach has been applied in sampling and identifying the algorithms. The results are groups with interchangeable elements. The outcomes convey two aspects of bullying: the form and the content or meaning. The form conveys the intentional intimidation against somebody, expressed at the level of texts by grammatical and lexical marks. This outcome has applicability in the forensic linguistics for establishing the intentionality of an action. Another outcome of form is a complex of graphemic variations essential in detecting harmful texts online. This research enriches the lexicon already known on the topic. The second aspect, the content, revealed the topics like threat, harassment, assault, or suicide. They are subcategories of a broader harmful content which is a constant concern for task forces and legislators at national and international levels. These topic – outcomes of the dataset are a valuable source of detection. The analysis of content revealed algorithms and lexicons which could be applied to other harmful contents. A third outcome of content are the conveyances of Stylistics, which is a rich source of discourse analysis of social media platforms. In conclusion, this corpus linguistics is structured on legislative criteria and could be used in various fields.

Keywords: corpus linguistics, cyberbullying, legislation, natural language processing, twitter

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