Search results for: molecular mechanisms

Authors: Dan Kanmegne

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Africa will become the most populated continent by the end of the century, with around 4 billion inhabitants. Food security and climate changes will become continental issues since agricultural practices depend on climate but also contribute to global emissions and land degradation. Agroforestry has been identified as a cost-efficient and reliable strategy to address these two issues. It is defined as the integrated management of trees and crops/animals in the same land unit. Agroforestry provides benefits in terms of goods (fruits, medicine, wood, etc.) and services (windbreaks, fertility, etc.), and is acknowledged to have a great potential for carbon sequestration; therefore it can be integrated into reduction mechanisms of carbon emissions. Particularly in sub-Saharan Africa, the constraint stands in the lack of information about both areas under agroforestry and the characterization (composition, structure, and management) of each agroforestry system at the country level. This study describes and quantifies “what is where?”, earliest to the quantification of carbon stock in different systems. Remote sensing (RS) is the most efficient approach to map such a dynamic technology as agroforestry since it gives relatively adequate and consistent information over a large area at nearly no cost. RS data fulfill the good practice guidelines of the Intergovernmental Panel On Climate Change (IPCC) that is to be used in carbon estimation. Satellite data are getting more and more accessible, and the archives are growing exponentially. To retrieve useful information to support decision-making out of this large amount of data, satellite data needs to be organized so to ensure fast processing, quick accessibility, and ease of use. A new solution is a data cube, which can be understood as a multi-dimensional stack (space, time, data type) of spatially aligned pixels and used for efficient access and analysis. A data cube for Burkina Faso has been set up from the cooperation project between the international service provider WASCAL and Germany, which provides an accessible exploitation architecture of multi-temporal satellite data. The aim of this study is to map and characterize agroforestry systems using the Burkina Faso earth observation data cube. The approach in its initial stage is based on an unsupervised image classification of a normalized difference vegetation index (NDVI) time series from 2010 to 2018, to stratify the country based on the vegetation. Fifteen strata were identified, and four samples per location were randomly assigned to define the sampling units. For safety reasons, the northern part will not be part of the fieldwork. A total of 52 locations will be visited by the end of the dry season in February-March 2020. The field campaigns will consist of identifying and describing different agroforestry systems and qualitative interviews. A multi-temporal supervised image classification will be done with a random forest algorithm, and the field data will be used for both training the algorithm and accuracy assessment. The expected outputs are (i) map(s) of agroforestry dynamics, (ii) characteristics of different systems (main species, management, area, etc.); (iii) assessment report of Burkina Faso data cube.

Keywords: agroforestry systems, Burkina Faso, earth observation data cube, multi-temporal image classification

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Authors: T. Ul Rehman, S. Agnello, F. M. Gelardi, M. M. Calvino, G. Lazzara, G. Buscarino, M. Cannas

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Metal-Organic Frameworks (MOFs) have emerged as promising candidates for detecting metal ions owing to their large surface area, customizable porosity, and diverse functionalities. In recent years, there has been a surge in research focused on MOFs with luminescent properties. These frameworks are constructed through coordinated bonding between metal ions and multi-dentate ligands, resulting in inherent fluorescent structures. Their luminescent behavior is influenced by factors like structural composition, surface morphology, pore volume, and interactions with target analytes, particularly metal ions. MOFs exhibit various sensing mechanisms, including photo-induced electron transfer (PET) and charge transfer processes such as ligand-to-metal (LMCT) and metal-to-ligand (MLCT) transitions. Among these, MIL-53(Al) stands out due to its flexibility, stability, and specific affinity towards certain metal ions, making it a promising platform for selective metal ion sensing. This study investigates the structural, thermal, and luminescent properties of MIL-53(Al) metal-organic framework (MOF) upon Fe3+ cation exchange. Two separate sets of samples were prepared to activate the MOF powder at different temperatures. The first set of samples, referred to as MIL-53(Al), activated (120°C), was prepared by activating the raw powder in a glass tube at 120°C for 12 hours and then sealing it. The second set of samples, referred to as MIL-53(Al), activated (300°C), was prepared by activating the MIL-53(Al) powder in a glass tube at 300°C for 70 hours. Additionally, 25 mg of MIL-53(Al) powder was dispersed in 5 mL of Fe3+ solution at various concentrations (0.1-100 mM) for the cation exchange experiment. The suspension was centrifuged for five minutes at 10,000 rpm to extract MIL-53(Al) powder. After three rounds of washing with ultrapure water, MIL-53(Al) powder was heated at 120°C for 12 hours. For PXRD and TGA analyses, a sample of the obtained MIL-53(Al) was used. We also activated the cation-exchanged samples for time-resolved photoluminescence (TRPL) measurements at two distinct temperatures (120 and 300°C) for comparative analysis. Powder X-ray diffraction patterns reveal amorphization in samples with higher Fe3+ concentrations, attributed to alterations in coordination environments and ion exchange dynamics. Thermal decomposition analysis shows reduced weight loss in Fe3+-exchanged MOFs, indicating enhanced stability due to stronger metal-ligand bonds and altered decomposition pathways. Raman spectroscopy demonstrates intensity decrease, shape disruption, and frequency shifts, indicative of structural perturbations induced by cation exchange. Photoluminescence spectra exhibit ligand-based emission (π-π* or n-π*) and ligand-to-metal charge transfer (LMCT), influenced by activation temperature and Fe3+ incorporation. Quenching of luminescence intensity and shorter lifetimes upon Fe3+ exchange result from structural distortions and Fe3+ binding to organic linkers. In a nutshell, this research underscores the complex interplay between composition, structure, and properties in MOFs, offering insights into their potential for diverse applications in catalysis, gas storage, and luminescent devices.

Keywords: Fe³⁺ cation exchange, luminescent metal-organic frameworks (LMOFs), MIL-53(Al), solid-state analysis

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Authors: Supriya Ambawat, Subaran Singh, C. Tara Satyavathi, B. S. Rajpurohit, Ummed Singh, Balraj Singh

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Pearl millet [Pennisetum glaucum (L.) R. Br.] is an important staple food of the arid and semiarid tropical regions of Asia, Africa, and Latin America. It is rightly termed as nutricereal as it has high nutrition value and a good source of carbohydrate, protein, fat, ash, dietary fiber, potassium, magnesium, iron, zinc, etc. Pearl millet has low prolamine fraction and is gluten free which is useful for people having a gluten allergy. It has several health benefits like reduction in blood pressure, thyroid, diabe¬tes, cardiovascular and celiac diseases but its direct consumption as food has significantly declined due to several reasons. Keeping this in view, it is important to reorient the ef¬forts to generate demand through value-addition and quality improvement and create awareness on the nutritional merits of pearl millet. In India, through Indian Council of Agricultural Research-All India Coordinated Research Project on Pearl millet, multilocational coordinated trials for developed hybrids were conducted at various centers. The gene banks of pearl millet contain varieties with high levels of iron and zinc which were used to produce new pearl millet varieties with elevated iron levels bred with the high‐yielding varieties. Thus, using breeding approaches and biochemical analysis, a total of 167 hybrids and 61 varieties were identified and released for cultivation in different agro-ecological zones of the country which also includes some biofortified hybrids rich in Fe and Zn. Further, using several biotechnological interventions such as molecular markers, next-generation sequencing (NGS), association mapping, nested association mapping (NAM), MAGIC populations, genome editing, genotyping by sequencing (GBS), genome wide association studies (GWAS) advancement in millet improvement has become possible by identifying and tagging of genes underlying a trait in the genome. Using DArT markers very high density linkage maps were constructed for pearl millet. Improved HHB67 has been released using marker assisted selection (MAS) strategies, and genomic tools were used to identify Fe-Zn Quantitative Trait Loci (QTL). The draft genome sequence of millet has also opened various ways to explore pearl millet. Further, genomic positions of significantly associated simple sequence repeat (SSR) markers with iron and zinc content in the consensus map is being identified and research is in progress towards mapping QTLs for flour rancidity. The sequence information is being used to explore genes and enzymatic pathways responsible for rancidity of flour. Thus, development and application of several biotechnological approaches along with biofortification can accelerate the genetic gain targets for pearl millet improvement and help improve its quality.

Keywords: Biotechnological approaches, genomic tools, malnutrition, MAS, nutricereal, pearl millet, sequencing.

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Authors: Betelhem M. Negede, Maarten Voors, Hugo De Groote, Bart Minten

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Farmers in Ethiopia produce most of their own food during one agricultural season per year. Therefore, they need to use on-farm storage technologies to bridge the lean season and benefit from price arbitrage. Maize stored using traditional storage bags offer no protection from insects and molds, leading to high storage losses. In Ethiopia access to and use of modern storage technologies are still limited, restraining farmers to benefit from local maize price fluctuations. We used a randomized controlled trial among 871 maize farmers to evaluate the impacts of Purdue Improved Crop Storage (PICS) bags, also known as hermetic bags, on storage losses, and especially on behavioral changes with respect to consumption, marketing, and income among maize farmers in Ethiopia. This study builds upon the limited previous experimental research that has tried to understand farmers’ grain storage and post-harvest losses and identify mechanisms behind the persistence of these challenges. Our main hypothesis is that access to PICS bags allows farmers to increase production, storage and maize income. Also delay the length of maize storage, reduce maize post-harvest losses and improve their food security. Our results show that even though farmers received only three PICS bags that represent 10percent of their total maize stored, they delay their length of maize storage for sales by two weeks. However, we find no treatment effect on maize income, suggesting that the arbitrage of two weeks is too small. Also, we do not find any reduction in storage losses due to farmers’ reaction by selling early and by using cheap and readily available but potentially harmful storage chemicals. Looking at the heterogeneity treatment effects between the treatment variable and highland and lowland villages, we find a decrease in the percentage of maize stored by 4 percent in the highland villages. This confirms that location specific factors, such as agro-ecology and proximity to markets are important factors that influence whether and how much of the harvest a farmer stores. These findings highlight the benefits of hermetic storage bags, by allowing farmers to make inter-temporal arbitrage and by reducing potential health risks from storage chemicals. The main policy recommendation that emanates from our study is that postharvest losses reduction throughout the whole value chain is an important pathway to food and income security in Sub-Saharan Africa (SSA). However, future storage loss interventions with hermetic storage technologies should take into account the agro-ecology of the study area and quantify storage losses beyond farmers self-reported losses, such as the count and weigh method. Finally, studies on hermetic storage technologies indicate positive impacts on post-harvest losses and in improving food security, but the adoption and use of these technologies is currently still low in SSA. Therefore, future works on the scaling up of hermetic bags, should consider reasons why farmers only use PICS bags to store grains for consumption, which is usually related to a safety-first approach or due to lack of incentives (higher price from maize not treated with chemicals), and no grain quality check.

Keywords: arbitrage, PICS hermetic bags, post-harvest storage loss, RCT

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Authors: Mohamed M. Zaki, Maha M. Hady

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Salmonella spp. have been categorized as the world’s biggest threats to human health and poultry products are mostly incriminated sources. In Egypt, it was found that S. enteritidis and S. typhimurium are the most prevalent ones in poultry farms. It is recommended to eliminate salmonella from living bird by competing for salmonella contamination in feed in order to establish a healthy gut. The Feed acidifiers are the group of feed additives containing low-molecular-weight organic acids and/ or their salts which act as performance promoters by lowering the pH in the gut, optimizes digestion and inhibit bacterial growth. The inclusion of organic acid in pure form nonetheless effective in feed, yet, it is difficult to handle in feed mills as it is corrosive and produce more losses during pelleting process. The current study aimed at to evaluate the impact of incorporation of sodium diformate (SDF) and a commercial acidifier, CA (a mixture of butyric and propionic acids and their ammonium salts) at 0.4% dietary levels on broilers performance and the control S. enteritidis infection. Two hundreds and seventy unsexed cobb chickens were allotted in one of three treatments (90/ group) which were, the control (no acidifier, C- &C+), the 0.4% SDF (SDF- & SDF +) and the 0.4% CA (CA- & CA +) dietary levels for 35 days. Before the allocation of the groups, ten extra birds and a diet sample were bacteriologically examined to ensure negative contamination with salmonella. The birds were raised on deep-litter separated pens and had free access to feed and water all the time. The experimentally formulated diets were kept at 40C. After 24h access to the different dietary treatments, all the birds in the positive groups (n=15/ replicate) were inoculated intra-crop with 0.2 ml of 24 h broth culture of S. entertidis containing 1X 107 organisms while the negative-treated groups were inoculated with the same amount of the negative broth and second inoculation was done at 22 d of age. Colocal swabs were collected individually from all birds 2 h pre-inoculation to assure the absence of salmonella, then 1, 3, 5, 7, 21 days post-inoculation to recover salmonella. Performance parameter (body weight gain and feed efficiency) were calculated. Mortalities were recorded and reisolation of the salmonella was adopted to ensure it was the inoculated ones. The results revealed that the dietary acidification with sodium diformate significantly improved broilers performance and tends to produce heavier birds as compared to the negative control and CA groups. Moreover, the dietary inclusion of both acidifiers at level of 0.4% was able to eliminate mortalities completely at the relevant inoculation time. Regarding the shedding of S. enteritidius in positive groups, the SDF treatment resulted in significant (p<0.05) cessation of the shedding at 3 days post-inoculation compared to 7 days post-inoculation for the CA-group. In conclusion, sodium diformate at 0.4% dietary level in broiler diets has a valuable effect not only on broilers performance but also by eliminating S. enteritidis the main source of salmonella contamination in poultry farms which is feed.

Keywords: acidifier, broilers, Salmonalla spp, sodium diformate

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Authors: Sara Camino, Fernando Vega, Mercedes Cano, Benito Navarrete, José A. Camino

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Carbon capture and storage (CCS) technologies should play a relevant role towards low-carbon systems in the European Union by 2030. Partial oxy-combustion emerges as a promising CCS approach to mitigate anthropogenic CO₂ emissions. Its advantages respect to other CCS technologies rely on the production of a higher CO₂ concentrated flue gas than these provided by conventional air-firing processes. The presence of more CO₂ in the flue gas increases the driving force in the separation process and hence it might lead to further reductions of the energy requirements of the overall CO₂ capture process. A higher CO₂ concentrated flue gas should enhance the CO₂ capture by chemical absorption in solvent kinetic and CO₂ cyclic capacity. They have impact on the performance of the overall CO₂ absorption process by reducing the solvent flow-rate required for a specific CO₂ removal efficiency. Lower solvent flow-rates decreases the reboiler duty during the regeneration stage and also reduces the equipment size and pumping costs. Moreover, R&D activities in this field are focused on novel solvents and blends that provide lower CO₂ absorption enthalpies and therefore lower energy penalties associated to the solvent regeneration. In this respect, sterically hindered amines are considered potential solvents for CO₂ capture. They provide a low energy requirement during the regeneration process due to its molecular structure. However, its absorption kinetics are slow and they must be promoted by blending with faster solvents such as monoethanolamine (MEA) and piperazine (PZ). In this work, the kinetic behavior of two sterically hindered amines were studied under partial oxy-combustion conditions and compared with MEA. A lab-scale semi-batch reactor was used. The CO₂ composition of the synthetic flue gas varied from 15%v/v – conventional coal combustion – to 60%v/v – maximum CO₂ concentration allowable for an optimal partial oxy-combustion operation. Firstly, 2-amino-2-methyl-1-propanol (AMP) showed a hybrid behavior with fast kinetics and a low enthalpy of CO₂ absorption. The second solvent was Isophrondiamine (IF), which has a steric hindrance in one of the amino groups. Its free amino group increases its cyclic capacity. In general, the presence of higher CO₂ concentration in the flue gas accelerated the CO₂ absorption phenomena, producing higher CO₂ absorption rates. In addition, the evolution of the CO2 loading also exhibited higher values in the experiments using higher CO₂ concentrated flue gas. The steric hindrance causes a hybrid behavior in this solvent, between both fast and slow kinetic solvents. The kinetics rates observed in all the experiments carried out using AMP were higher than MEA, but lower than the IF. The kinetic enhancement experienced by AMP at a high CO2 concentration is slightly over 60%, instead of 70% – 80% for IF. AMP also improved its CO₂ absorption capacity by 24.7%, from 15%v/v to 60%v/v, almost double the improvements achieved by MEA. In IF experiments, the CO₂ loading increased around 10% from 15%v/v to 60%v/v CO₂ and it changed from 1.10 to 1.34 mole CO₂ per mole solvent, more than 20% of increase. This hybrid kinetic behavior makes AMP and IF promising solvents for partial oxy–combustion applications.

Keywords: absorption, carbon capture, partial oxy-combustion, solvent

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Authors: Siba Soren, Purnendu Parhi

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Today, the world is facing a severe challenge due to depletion of traditional fossil fuels. Scientists across the globe are working for a solution that involves a dramatic shift to practical and environmentally sustainable energy sources. High-capacity energy systems, such as metal-air batteries, fuel cells, are highly desirable to meet the urgent requirement of sustainable energies. Among the fuel cells, Direct methanol fuel cells (DMFCs) are recognized as an ideal power source for mobile applications and have received considerable attention in recent past. In this advanced electrochemical energy conversion technologies, Oxygen Reduction Reaction (ORR) is of utmost importance. However, the poor kinetics of cathodic ORR in DMFCs significantly hampers their possibilities of commercialization. The oxygen is reduced in alkaline medium either through a 4-electron (equation i) or a 2-electron (equation ii) reduction pathway at the cathode ((i) O₂ + 2H₂O + 4e⁻ → 4OH⁻, (ii) O₂ + H₂O + 2e⁻ → OH⁻ + HO₂⁻ ). Due to sluggish ORR kinetics the ability to control the reduction of molecular oxygen electrocatalytically is still limited. The electrocatalytic ORR starts with adsorption of O₂ on the electrode surface followed by O–O bond activation/cleavage and oxide removal. The reaction further involves transfer of 4 electrons and 4 protons. The sluggish kinetics of ORR, on the one hand, demands high loading of precious metal-containing catalysts (e.g., Pt), which unfavorably increases the cost of these electrochemical energy conversion devices. Therefore, synthesis of active electrocatalyst with an increase in ORR performance is need of the hour. In the recent literature, there are many reports on transition metal oxide (TMO) based ORR catalysts for their high activity TMOs are also having drawbacks like low electrical conductivity, which seriously affects the electron transfer process during ORR. It was found that 2D graphene layer is having high electrical conductivity, large surface area, and excellent chemical stability, appeared to be an ultimate choice as support material to enhance the catalytic performance of bare metal oxide. g-C₃N₄ is also another candidate that has been used by the researcher for improving the ORR performance of metal oxides. This material provides more active reaction sites than other N containing carbon materials. Rare earth oxide like CeO₂ is also a good candidate for studying the ORR activity as the metal oxide not only possess unique electronic properties but also possess catalytically active sites. Here we will discuss the ORR performance (in alkaline medium) of N-rGO/C₃N₄ supported nano Cerium Oxides hybrid synthesized by microwave assisted Solvothermal method. These materials exhibit superior electrochemical stability and methanol tolerance capability to that of commercial Pt/C.

Keywords: oxygen reduction reaction, electrocatalyst, cerium oxide, graphene

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Authors: Michael Brave, Mark Kroll, Steven Karch, Charles Wetli, Michael Graham, Sebastian Kunz, Dorin Panescu

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Background: Conducted electrical weapons (CEW) are now used in 107 countries and are a common law enforcement less-lethal force practice in the United Kingdom (UK), United States of America (USA), Canada, Australia, New Zealand, and others. Use of these devices is rarely temporally associated with the occurrence of sudden arrest-related deaths (ARD). Because such deaths are uncommon, few Medical Examiners (MEs) ever encounter one, and even fewer offices have established comprehensive investigative protocols. Without sufficient scientific data, the role, if any, played by a CEW in a given case is largely supplanted by conjecture often defaulting to a CEW-induced fatal cardiac arrhythmia. In addition to the difficulty in investigating individual deaths, the lack of information also detrimentally affects being able to define and evaluate the ARD cohort generally. More comprehensive, better information leads to better interpretation in individual cases and also to better research. The purpose of this presentation is to provide MEs with a comprehensive evidence-based checklist to assist in the assessment of CEW-ARD cases. Methods: PUBMED and Sociology/Criminology data bases were queried to find all medical, scientific, electrical, modeling, engineering, and sociology/criminology peer-reviewed literature for mentions of CEW or synonymous terms. Each paper was then individually reviewed to identify those that discussed possible bioelectrical mechanisms relating CEW to ARD. A Naranjo-type pharmacovigilance algorithm was also employed, when relevant, to identify and quantify possible direct CEW electrical myocardial stimulation. Additionally, CEW operational manuals and training materials were reviewed to allow incorporation of CEW-specific technical parameters. Results: Total relevant PUBMED citations of CEWs were less than 250, and reports of death extremely rare. Much relevant information was available from Sociology/Criminology data bases. Once the relevant published papers were identified, and reviewed, we compiled an annotated checklist of data that we consider critical to a thorough CEW-involved ARD investigation. Conclusion: We have developed an evidenced-based checklist that can be used by MEs and their staffs to assist them in identifying, collecting, documenting, maintaining, and objectively analyzing the role, if any, played by a CEW in any specific case of sudden death temporally associated with the use of a CEW. Even in cases where the collected information is deemed by the ME as insufficient for formulating an opinion or diagnosis to a reasonable degree of medical certainty, information collected as per the checklist will often be adequate for other stakeholders to use as a basis for informed decisions. Having reviewed the appropriate materials in a significant number of cases careful examination of the heart and brain is likely adequate. Channelopathy testing should be considered in some cases, however it may be considered cost prohibitive (aprox $3000). Law enforcement agencies may want to consider establishing a reserve fund to help manage such rare cases. The expense may stay the enormous costs associated with incident-precipitated litigation.

Keywords: ARD, CEW, police, TASER

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Authors: Uraib Sharaha, Ahmad Salman, Eladio Rodriguez-Diaz, Elad Shufan, Klaris Riesenberg, Irving J. Bigio, Mahmoud Huleihel

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Antimicrobial drugs have played an indispensable role in controlling illness and death associated with infectious diseases in animals and humans. However, the increasing resistance of bacteria to a broad spectrum of commonly used antibiotics has become a global healthcare problem. Many antibiotics had lost their effectiveness since the beginning of the antibiotic era because many bacteria have adapted defenses against these antibiotics. Rapid determination of antimicrobial susceptibility of a clinical isolate is often crucial for the optimal antimicrobial therapy of infected patients and in many cases can save lives. The conventional methods for susceptibility testing require the isolation of the pathogen from a clinical specimen by culturing on the appropriate media (this culturing stage lasts 24 h-first culturing). Then, chosen colonies are grown on media containing antibiotic(s), using micro-diffusion discs (second culturing time is also 24 h) in order to determine its bacterial susceptibility. Other methods, genotyping methods, E-test and automated methods were also developed for testing antimicrobial susceptibility. Most of these methods are expensive and time-consuming. Fourier transform infrared (FTIR) microscopy is rapid, safe, effective and low cost method that was widely and successfully used in different studies for the identification of various biological samples including bacteria; nonetheless, its true potential in routine clinical diagnosis has not yet been established. The new modern infrared (IR) spectrometers with high spectral resolution enable measuring unprecedented biochemical information from cells at the molecular level. Moreover, the development of new bioinformatics analyses combined with IR spectroscopy becomes a powerful technique, which enables the detection of structural changes associated with resistivity. The main goal of this study is to evaluate the potential of the FTIR microscopy in tandem with machine learning algorithms for rapid and reliable identification of bacterial susceptibility to antibiotics in time span of few minutes. The UTI E.coli bacterial samples, which were identified at the species level by MALDI-TOF and examined for their susceptibility by the routine assay (micro-diffusion discs), are obtained from the bacteriology laboratories in Soroka University Medical Center (SUMC). These samples were examined by FTIR microscopy and analyzed by advanced statistical methods. Our results, based on 700 E.coli samples, were promising and showed that by using infrared spectroscopic technique together with multivariate analysis, it is possible to classify the tested bacteria into sensitive and resistant with success rate higher than 90% for eight different antibiotics. Based on these preliminary results, it is worthwhile to continue developing the FTIR microscopy technique as a rapid and reliable method for identification antibiotic susceptibility.

Keywords: antibiotics, E.coli, FTIR, multivariate analysis, susceptibility, UTI

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Authors: Maryam Hajrezaie, Mahmood Ameen Abdulla, Nazia Abdul Majid, Hapipa Mohd Ali, Pouya Hassandarvish, Maryam Zahedi Fard

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Background: Colon cancer is one of the most prevalent cancers in the world and is the third leading cause of death among cancers in both males and females. The incidence of colon cancer is ranked fourth among all cancers but varies in different parts of the world. Cancer chemoprevention is defined as the use of natural or synthetic compounds capable of inducing biological mechanisms necessary to preserve genomic fidelity. Andrographolide is the major labdane diterpenoidal constituent of the plant Andrographis paniculata (family Acanthaceae), used extensively in the traditional medicine. Extracts of the plant and their constituents are reported to exhibit a wide spectrum of biological activities of therapeutic importance. Laboratory animal model studies have provided evidence that Andrographolide play a role in inhibiting the risk of certain cancers. Objective: Our aim was to evaluate the chemopreventive efficacy of the Andrographolide in the AOM induced rat model. Methods: To evaluate inhibitory properties of andrographolide on colonic aberrant crypt foci (ACF), five groups of 7-week-old male rats were used. Group 1 (control group) were fed with 10% Tween 20 once a day, Group 2 (cancer control) rats were intra-peritoneally injected with 15 mg/kg Azoxymethan, Gropu 3 (drug control) rats were injected with 15 mg/kg azoxymethan and 5-Flourouracil, Group 4 and 5 (experimental groups) were fed with 10 and 20 mg/kg andrographolide each once a day. After 1 week, the treatment group rats received subcutaneous injections of azoxymethane, 15 mg/kg body weight, once weekly for 2 weeks. Control rats were continued on Tween 20 feeding once a day and experimental groups 10 and 20 mg/kg andrographolide feeding once a day for 8 weeks. All rats were sacrificed 8 weeks after the azoxymethane treatment. Colons were evaluated grossly and histopathologically for ACF. Results: Administration of 10 mg/kg and 20 mg/kg andrographolide were found to be effectively chemoprotective, as evidenced microscopily and biochemically. Andrographolide suppressed total colonic ACF formation up to 40% to 60%, respectively, when compared with control group. Pre-treatment with andrographolide, significantly reduced the impact of AOM toxicity on plasma protein and urea levels as well as on plasma aspartate aminotransferase (AST), alanine aminotransferase (ALT), lactate dehydrogenase (LDH) and gamma-glutamyl transpeptidase (GGT) activities. Grossly, colorectal specimens revealed that andrographolide treatments decreased the mean score of number of crypts in AOM-treated rats. Importantly, rats fed andrographolide showed 75% inhibition of foci containing four or more aberrant crypts. The results also showed a significant increase in glutathione (GSH), superoxide dismutase (SOD), nitric oxide (NO), and Prostaglandin E2 (PGE2) activities and a decrease in malondialdehyde (MDA) level. Histologically all treatment groups showed a significant decrease of dysplasia as compared to control group. Immunohistochemical staining showed up-regulation of Hsp70 and down-regulation of Bax proteins. Conclusion: The current study demonstrated that Andrographolide reduce the number of ACF. According to these data, Andrographolide might be a promising chemoprotective activity, in a model of AOM-induced in ACF.

Keywords: chemopreventive, andrographolide, colon cancer, aberrant crypt foci (ACF)

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Authors: Luis Castiella, Mariano Rueda, Catalina Palacio

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The world’s rapid urbanisation represents an excellent opportunity to implement initiatives that are oriented towards a country’s general development. However, this phenomenon has created considerable pressure on current urban models, pushing them nearer to a crisis. As a result, several factors usually associated with underdevelopment have been steadily rising. Moreover, actions taken by public authorities have not been able to keep up with the speed of urbanisation, which has impeded them from meeting the demands of society, responding with reactionary policies instead of with coordinated, organised efforts. In contrast, the concept of a Smart City which emerged around two decades ago, in principle, represents a city that utilises innovative technologies to remedy the everyday issues of the citizen, empowering them with the newest available technology and information. This concept has come to adopt a wider meaning, including human and social capital, as well as productivity, economic growth, quality of life, environment and participative governance. These developments have also disrupted the management of institutions such as academia, which have become key in generating scientific advancements that can solve pressing problems, and in forming a specialised class that is able to follow up on these breakthroughs. In this light, the Ministry of Modernisation of the Argentinian Nation has created a model that is rooted in the concept of a ‘Smart City’. This effort considered all the dimensions that are at play in an urban environment, with careful monitoring of each sub-dimensions in order to establish the government’s priorities and improving the effectiveness of its operations. In an attempt to ameliorate the overall efficiency of the country’s economic and social development, these focused initiatives have also encouraged citizen participation and the cooperation of the private sector: replacing short-sighted policies with some that are coherent and organised. This process was developed gradually. The first stage consisted in building the model’s structure; the second, at applying the method created on specific case studies and verifying that the mechanisms used respected the desired technical and social aspects. Finally, the third stage consists in the repetition and subsequent comparison of this experiment in order to measure the effects on the ‘treatment group’ over time. The first trial was conducted on 717 municipalities and evaluated the dimension of Governance. Results showed that levels of governmental maturity varied sharply with relation to size: cities with less than 150.000 people had a strikingly lower level of governmental maturity than cities with more than 150.000 people. With the help of this analysis, some important trends and target population were made apparent, which enabled the public administration to focus its efforts and increase its probability of being successful. It also permitted to cut costs, time, and create a dynamic framework in tune with the population’s demands, improving quality of life with sustained efforts to develop social and economic conditions within the territorial structure.

Keywords: composite index, comprehensive model, smart cities, strategic framework

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Authors: T. N. Tran Thi, J. Morse, C. Detlefs, P. K. Cook, C. Yıldırım, A. C. Jakobsen, T. Zhou, J. Hartwig, V. Zurbig, D. Caliste, B. Fernandez, D. Eon, O. Loto, M. L. Hicks, A. Pakpour-Tabrizi, J. Baruchel

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The ability to grow boron-doped diamond epilayers of high crystalline quality is a prerequisite for the fabrication of diamond power electronic devices, in particular high voltage diodes and metal-oxide-semiconductor (MOS) transistors. Boron and intrinsic diamond layers are homoepitaxially overgrown by microwave assisted chemical vapour deposition (MWCVD) on single crystal high pressure, high temperature (HPHT) grown bulk diamond substrates. Various epilayer thicknesses were grown, with dopant concentrations ranging from 1021 atom/cm³ at nanometer thickness in the case of 'delta doping', up 1016 atom/cm³ and 50µm thickness or high electric field drift regions. The crystalline quality of these overgrown layers as regards defects, strain, distortion… is critical for the device performance through its relation to the final electrical properties (Hall mobility, breakdown voltage...). In addition to the optimization of the epilayer growth conditions in the MWCVD reactor, other important questions related to the crystalline quality of the overgrown layer(s) are: 1) what is the dependence on the bulk quality and surface preparation methods of the HPHT diamond substrate? 2) how do defects already present in the substrate crystal propagate into the overgrown layer; 3) what types of new defects are created during overgrowth, what are their growth mechanisms, and how can these defects be avoided? 4) how can we relate in a quantitative manner parameters related to the measured crystalline quality of the boron doped layer to the electronic properties of final processed devices? We describe synchrotron-based techniques developed to address these questions. These techniques allow the visualization of local defects and crystal distortion which complements the data obtained by other well-established analysis methods such as AFM, SIMS, Hall conductivity…. We have used Grazing Incidence X-ray Diffraction (GIXRD) at the ID01 beamline of the ESRF to study lattice parameters and damage (strain, tilt and mosaic spread) both in diamond substrate near surface layers and in thick (10–50 µm) overgrown boron doped diamond epi-layers. Micro- and nano-section topography have been carried out at both the BM05 and ID06-ESRF) beamlines using rocking curve imaging techniques to study defects which have propagated from the substrate into the overgrown layer(s) and their influence on final electronic device performance. These studies were performed using various commercially sourced HPHT grown diamond substrates, with the MWCVD overgrowth carried out at the Fraunhofer IAF-Germany. The synchrotron results are in good agreement with low-temperature (5°K) cathodoluminescence spectroscopy carried out on the grown samples using an Inspect F5O FESEM fitted with an IHR spectrometer.

Keywords: synchrotron X-ray diffaction, crystalline quality, defects, diamond overgrowth, rocking curve imaging

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Authors: Shaista Suhail

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As cancer populations is increasing sharply, the incidence of oral squamous cell carcinoma (OSCC) has also been expected to increase. Oral carcinogenesis is a highly complex, multistep process which involves accumulation of genetic alterations that lead to the induction of proteins promoting cell growth (encoded by oncogenes), increased enzymatic (telomerase) activity promoting cancer cell proliferation. The global increase in frequency and mortality, as well as the poor prognosis of oral squamous cell carcinoma, has intensified current research efforts in the field of prevention and early detection of this disease. The advances in the understanding of the molecular basis of oral cancer should help in the identification of new markers. The study of the carcinogenic process of the oral cancer, including continued analysis of new genetic alterations, along with their temporal sequencing during initiation, promotion and progression, will allow us to identify new diagnostic and prognostic factors, which will provide a promising basis for the application of more rational and efficient treatments. Telomerase activity has been readily found in most cancer biopsies, in premalignant lesions or germ cells. Activity of telomerase is generally absent in normal tissues. It is known to be induced upon immortalization or malignant transformation of human cells such as in oral cancer cells. Maintenance of telomeres plays an essential role during transformation of precancer to malignant stage. Mammalian telomeres, a specialized nucleoprotein structures are composed of large conctamers of the guanine-rich sequence 5_-TTAGGG-3_. The roles of telomeres in regulating both stability of genome and replicative immortality seem to contribute in essential ways in cancer initiation and progression. It is concluded that activity of telomerase can be used as a biomarker for diagnosis of malignant oral cancer and a target for inactivation in chemotherapy or gene therapy. Its expression will also prove to be an important diagnostic tool as well as a novel target for cancer therapy. The activation of telomerase may be an important step in tumorgenesis which can be controlled by inactivating its activity during chemotherapy. The expression and activity of telomerase are indispensable for cancer development. There are no drugs which can effect extremely to treat oral cancers. There is a general call for new emerging drugs or methods that are highly effective towards cancer treatment, possess low toxicity, and have a minor environment impact. Some novel natural products also offer opportunities for innovation in drug discovery. Natural compounds isolated from medicinal plants, as rich sources of novel anticancer drugs, have been of increasing interest with some enzyme (telomerase) blockage property. The alarming reports of cancer cases increase the awareness amongst the clinicians and researchers pertaining to investigate newer drug with low toxicity.

Keywords: oral carcinoma, telomere, telomerase, blockage

Procedia PDF Downloads 150

Authors: Irina Deputat, Anatoly Gribanov, Yuliya Dzhos, Alexandra Nekhoroshkova, Tatyana Yemelianova, Irina Bolshevidtseva, Irina Deryabina, Yana Kereush, Larisa Startseva, Tatyana Bagretsova, Irina Ikonnikova

Abstract:

In the modern world the number of elderly people increases. Preservation of functionality of an organism in the elderly becomes very important now. During aging the higher cortical functions such as feelings, perception, attention, memory, and ideation are gradual decrease. It is expressed in the rate of information processing reduction, volume of random access memory loss, ability to training and storing of new information decrease. Perspective directions in studying of aging neurophysiological parameters are brain imaging: computer electroencephalography, neuroenergy mapping of a brain, and also methods of studying of a neurodynamic brain processes. Research aim – to study features of a brain aging in elderly people by electroencephalogram (EEG) and the DC-potential level. We examined 130 people aged 55 - 74 years that did not have psychiatric disorders and chronic states in a decompensation stage. EEG was recorded with a 128-channel GES-300 system (USA). EEG recordings are collected while the participant sits at rest with their eyes closed for 3 minutes. For a quantitative assessment of EEG we used the spectral analysis. The range was analyzed on delta (0,5–3,5 Hz), a theta - (3,5–7,0 Hz), an alpha 1-(7,0–11,0 Hz) an alpha 2-(11–13,0 Hz), beta1-(13–16,5 Hz) and beta2-(16,5–20 Hz) ranges. In each frequency range spectral power was estimated. The 12-channel hardware-software diagnostic ‘Neuroenergometr-KM’ complex was applied for registration, processing and the analysis of a brain constant potentials level. The DC-potential level registered in monopolar leads. It is revealed that the EEG of elderly people differ in higher rates of spectral power in the range delta (р < 0,01) and a theta - (р < 0,05) rhythms, especially in frontal areas in aging. By results of the comparative analysis it is noted that elderly people 60-64 aged differ in higher values of spectral power alfa-2 range in the left frontal and central areas (р < 0,05) and also higher values beta-1 range in frontal and parieto-occipital areas (р < 0,05). Study of a brain constant potential level distribution revealed increase of total energy consumption on the main areas of a brain. In frontal leads we registered the lowest values of constant potential level. Perhaps it indicates decrease in an energy metabolism in this area and difficulties of executive functions. The comparative analysis of a potential difference on the main assignments testifies to unevenness of a lateralization of a brain functions at elderly people. The results of a potential difference between right and left hemispheres testify to prevalence of the left hemisphere activity. Thus, higher rates of functional activity of a cerebral cortex are peculiar to people of early advanced age (60-64 years) that points to higher reserve opportunities of central nervous system. By 70 years there are age changes of a cerebral power exchange and level of electrogenesis of a brain which reflect deterioration of a condition of homeostatic mechanisms of self-control and the program of processing of the perceptual data current flow.

Keywords: brain, DC-potential level, EEG, elderly people

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Authors: Aurora Sheehy, Caitlin Prince

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Within current orthodox medical protocols, trauma and mental health issues are deemed to reside within the realm of cognitive or psychological therapists and are marginalised in these areas, in part due to limited drugs option available, mostly manipulating neurotransmitters or sedating patients to reduce symptoms. By contrast, this research presents examples from the clinical practice of how trauma can be assessed and treated physiologically. Adverse Childhood Experiences (ACEs) are a tally of different types of abuse and neglect. It has been used as a measurable and reliable predictor of the likelihood of the development of autoimmune disease. It is a direct way to demonstrate reliably the health impact of traumatic life experiences. A second assessment tool is Allostatic Load, which refers to the cumulative effects that chronic stress has on mental and physical health. It records the decline of an individual’s physiological capacity to cope with their experience. It uses a specific grouping of serum testing and physical measures. It includes an assessment of neuroendocrine, cardiovascular, immune and metabolic systems. Allostatic load demonstrates the health impact that trauma has throughout the body. It forms part of an initial intake assessment in clinical practice and could also be used in research to evaluate treatment. Examining medicinal plants for their physiological, neurological and somatic effects through the lens of Polyvagal theory offers new opportunities for trauma treatments. In situations where Polyvagal theory recommends activities and exercises to enable parasympathetic activation, many herbs that affect Effector Memory T (TEM) cells also enact these responses. Traditional or Indigenous European herbs show the potential to support the polyvagal tone, through multiple mechanisms. As the ventral vagal nerve reaches almost every major organ, plants that have actions on these tissues can be understood via their polyvagal actions, such as monoterpenes as agents to improve respiratory vagal tone, cyanogenic glycosides to reset polyvagal tone, volatile oils rich in phenyl methyl esters improve both sympathetic and parasympathetic tone, bitters activate gut function and can strongly promote parasympathetic regulation. Auricular Acupuncture uses a system of somatotopic mapping of the auricular surface overlaid with an image of an inverted foetus with each body organ and system featured. Given that the concha of the auricle is the only place on the body where the Vagus Nerve neurons reach the surface of the skin, several investigators have evaluated non-invasive, transcutaneous electrical nerve stimulation (TENS) at auricular points. Drawn from an interdisciplinary evidence base and developed through clinical practice, these assessment and treatment tools are examples of practitioners in the field innovating out of necessity for the best outcomes for patients. This paper draws on case studies to direct future research.

Keywords: polyvagal, auricular acupuncture, trauma, herbs

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Authors: Oleg Kabantsev, Karomatullo Umarov

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The engineering analysis of earthquake consequences demonstrates a significantly different level of damage to load-bearing systems of different types. Buildings with reinforced concrete columns and separate shear-walls receive the highest level of damage. Traditional methods for predicting damage under earthquake excitations do not provide an answer to the question about the reasons for the increased vulnerability of reinforced concrete frames with shear-walls bearing systems. Thus, the study of the problem of formation and accumulation of damages in the structures reinforced concrete frame with shear-walls requires the use of new methods of assessment of the stress-strain state, as well as new approaches to the calculation of the distribution of forces and stresses in the load-bearing system based on account of various mechanisms of elastic-plastic deformation of reinforced concrete columns and walls. The results of research into the processes of non-linear deformation of structures with a transition to destruction (collapse) will allow to substantiate the characteristics of limit states of various structures forming an earthquake-resistant load-bearing system. The research of elastic-plastic deformation processes of reinforced concrete structures of frames with shear-walls is carried out on the basis of experimentally established parameters of limit deformations of concrete and reinforcement under dynamic excitations. Limit values of deformations are defined for conditions under which local damages of the maximum permissible level are formed in constructions. The research is performed by numerical methods using ETABS software. The research results indicate that under earthquake excitations, plastic deformations of various levels are formed in various groups of elements of the frame with the shear-wall load-bearing system. During the main period of seismic effects in the shear-wall elements of the load-bearing system, there are insignificant volumes of plastic deformations, which are significantly lower than the permissible level. At the same time, plastic deformations are formed in the columns and do not exceed the permissible value. At the final stage of seismic excitations in shear-walls, the level of plastic deformations reaches values corresponding to the plasticity coefficient of concrete , which is less than the maximum permissible value. Such volume of plastic deformations leads to an increase in general deformations of the bearing system. With the specified parameters of the deformation of the shear-walls in concrete columns, plastic deformations exceeding the limiting values develop, which leads to the collapse of such columns. Based on the results presented in this study, it can be concluded that the application seismic-force-reduction factor, common for the all load-bearing system, does not correspond to the real conditions of formation and accumulation of damages in elements of the load-bearing system. Using a single coefficient of seismic-force-reduction factor leads to errors in predicting the seismic resistance of reinforced concrete load-bearing systems. In order to provide the required level of seismic resistance buildings with reinforced concrete columns and separate shear-walls, it is necessary to use values of the coefficient of seismic-force-reduction factor differentiated by types of structural groups.1

Keywords: reinforced concrete structures, earthquake excitation, plasticity coefficients, seismic-force-reduction factor, nonlinear dynamic analysis

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Authors: Daniel Tscharnuter, Eliza Truszkiewicz, Gerald Pinter

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High-quality surfaces of plastic parts can be achieved in a very cost-effective manner using in-mold processes, where e.g. scratch resistant or high gloss polymer films are pre-formed and subsequently receive their support structure by injection molding. The pre-forming may be done by high-pressure forming. In this process, a polymer sheet is heated and subsequently formed into the mold by pressurized air. Due to the heat transfer to the cooled mold the polymer temperature drops below its glass transition temperature. This ensures that the deformed microstructure is retained after depressurizing, giving the sheet its final formed shape. The development of a forming process relies heavily on the experience of engineers and trial-and-error procedures. Repeated mold design and testing cycles are however both time- and cost-intensive. It is, therefore, desirable to study the process using reliable computer simulations. Through simulations, the construction of the mold and the effect of various process parameters, e.g. temperature levels, non-uniform heating or timing and magnitude of pressure, on the deformation of the polymer sheet can be analyzed. Detailed knowledge of the deformation is particularly important in the forming of polymer films with integrated electro-optical functions. Care must be taken in the placement of devices, sensors and electrical and optical paths, which are far more sensitive to deformation than the polymers. Reliable numerical prediction of the deformation of the polymer sheets requires sophisticated material models. Polymer films are often either transversely isotropic or orthotropic due to molecular orientations induced during manufacturing. The anisotropic behavior affects the resulting strain field in the deformed film. For example, parts of the same shape but different strain fields may be created by varying the orientation of the film with respect to the mold. The numerical simulation of the high-pressure forming of such films thus requires material models that can capture the nonlinear anisotropic mechanical behavior. There are numerous commercial polymer grades for the engineers to choose from when developing a new part. The effort required for comprehensive material characterization may be prohibitive, especially when several materials are candidates for a specific application. We, therefore, propose a class of models for compressible hyperelasticity, which may be determined from basic experimental data and which can capture key features of the mechanical response. Invariant-based hyperelastic models with a reduced number of invariants are formulated in a semi-numerical way, such that the models are determined from a single uniaxial tensile tests for isotropic materials, or two tensile tests in the principal directions for transversely isotropic or orthotropic materials. The simulation of the high pressure forming of an orthotropic polymer film is finally done using an orthotropic formulation of the hyperelastic model.

Keywords: hyperelastic, anisotropic, polymer film, thermoforming

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Authors: Sylvie Michel, Emmanuelle Gagnou, Joanne Hamet

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Researchers in the fields of AI and Robotics frequently encounter ethical dilemmas throughout their research endeavors. Various ethical challenges have been pinpointed in the existing literature, including biases and discriminatory outcomes, diffusion of responsibility, and a deficit in transparency within AI operations. This research aims to pinpoint these ethical quandaries faced by researchers and shed light on the mechanisms behind ethical decision-making in the research process. By synthesizing insights from existing literature and acknowledging prevalent shortcomings, such as overlooking the heterogeneous nature of decision-making, non-accumulative results, and a lack of consensus on numerous factors due to limited empirical research, the objective is to conceptualize and validate a model. This model will incorporate influences from individual perspectives and situational contexts, considering potential moderating factors in the ethical decision-making process. Qualitative analyses were conducted based on direct observation of an AI/Robotics research team focusing on collaborative robotics for several months. Subsequently, semi-structured interviews with 16 team members were conducted. The entire process took place during the first semester of 2023. Observations were analyzed using an analysis grid, and the interviews underwent thematic analysis using Nvivo software. An initial finding involves identifying the ethical challenges that AI/robotics researchers confront, underlining a disparity between practical applications and theoretical considerations regarding ethical dilemmas in the realm of AI. Notably, researchers in AI prioritize the publication and recognition of their work, sparking the genesis of these ethical inquiries. Furthermore, this article illustrated that researchers tend to embrace a consequentialist ethical framework concerning safety (for humans engaging with robots/AI), worker autonomy in relation to robots, and the societal implications of labor (can robots displace jobs?). A second significant contribution entails proposing a model for ethical decision-making within the AI/Robotics research sphere. The model proposed adopts a process-oriented approach, delineating various research stages (topic proposal, hypothesis formulation, experimentation, conclusion, and valorization). Across these stages and the ethical queries, they entail, a comprehensive four-point comprehension of ethical decision-making is presented: recognition of the moral quandary; moral judgment, signifying the decision-maker's aptitude to discern the morally righteous course of action; moral intention, reflecting the ability to prioritize moral values above others; and moral behavior, denoting the application of moral intention to the situation. Variables such as political inclinations ((anti)-capitalism, environmentalism, veganism) seem to wield significant influence. Moreover, age emerges as a noteworthy moderating factor. AI and robotics researchers are continually confronted with ethical dilemmas during their research endeavors, necessitating thoughtful decision-making. The contribution involves introducing a contextually tailored model, derived from meticulous observations and insightful interviews, enabling the identification of factors that shape ethical decision-making at different stages of the research process.

Keywords: ethical decision making, artificial intelligence, robotics, research

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Authors: Ashok Kumar, Parveen Parveen

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India is bestowed with an extremely high population of plant species with medicinal value and even has two biodiversity hotspots. Indian systems of medicine including Ayurveda, Siddha and Unani have historically been serving humankind across the world since time immemorial. About 1500 plant species have well been documented in Ayurvedic Nighantus as official medicinal plants. Additionally, several hundred species of plants are being routinely used as medicines by local people especially tribes living in and around forests. The natural resources for medicinal plants have unscientifically been over-exploited forcing rapid depletion in their genetic diversity. Moreover, renewed global interest in herbal medicines may even lead to additional depletion of medicinal plant wealth of the country, as about 95% collection of medicinal plants for pharmaceutical preparation is being carried out from natural forests. On the other hand, huge export market of medicinal and aromatic plants needs to be seriously tapped for enhancing inflow of foreign currency. Asparagus racemosus Willd., a member of family Liliaceae, is one of thirty-two plant species that have been identified as priority species for cultivation and conservation by the National Medicinal Plant Board (NMPB), Government of India. Though attention is being focused on standardization of agro-techniques and extraction methods, little has been designed on genetic improvement and selection of desired types with higher root production and saponin content, a basic ingredient of medicinal value. The saponin not only improves defense mechanisms and controls diabetes but the roots of this species promote secretion of breast milk, improved lost body weight and considered as an aphrodisiac. There is ample scope for genetic improvement of this species for enhancing productivity substantially, qualitatively and quantitatively. It is emphasized to select desired genotypes with sufficient genetic diversity for important economic traits. Hybridization between two genetically divergent genotypes could result in the synthesis of new F1 hybrids consisting of useful traits of both the parents. The evaluation of twenty seed sources of Asparagus racemosus assembled different geographical locations of India revelled high degree of variability for traits of economic importance. The maximum genotypic and phenotypic variance was observed for shoot height among shoot related traits and for root length among root related traits. The shoot height, genotypic variance, phenotypic variance, genotypic coefficient of variance, the phenotypic coefficient of variance was recorded to be 231.80, 3924.80, 61.26 and 1037.32, respectively, where those of the root length were 9.55, 16.80, 23.46 and 41.27, respectively. The maximum genetic advance and genetic gain were obtained for shoot height among shoot-related traits and root length among root-related traits. Index values were developed for all seed sources based on the four most important traits, and Panthnagar (Uttrakhand), Jodhpur (Rajasthan), Dehradun (Uttarakhand), Chandigarh (Punjab), Jammu (Jammu & Kashmir) and Solan (Himachal Pradesh) were found to be promising seed sources.

Keywords: asparagus, genetic, genotypes, variance

Procedia PDF Downloads 111

Authors: Ivanor Zardo, Fernanda Walper Da Cunha, Júlia Sarkis, Ligia Damasceno Ferreira Marczak

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Lipid oxidation is one of the most important deteriorating processes in oil industry, resulting in the losses of nutritional value of oils as well as changes in color, flavor and other physiological properties. Autoxidation of lipids occurs naturally between molecular oxygen and the unsaturation of fatty acids, forming fat-free radicals, peroxide free radicals and hydroperoxides. In order to avoid the lipid oxidation in vegetable oils, synthetic antioxidants such as butylated hydroxyanisole (BHA), butylated hydroxytoluene (BHT) and tertiary butyl hydro-quinone (TBHQ) are commonly used. However, the use of synthetic antioxidants has been associated with several health side effects and toxicity. The use of natural antioxidants as stabilizers of vegetable oils is being suggested as a sustainable alternative to synthetic antioxidants. The alternative that has been studied is the use of natural extracts obtained mainly from fruits, vegetables and seeds, which have a well-known antioxidant activity related mainly to the presence of phenolic compounds. The sunflower seed cake is rich in phenolic compounds (1 4% of the total mass), being the chlorogenic acid the major constituent. The aim of this study was to evaluate the in vitro application of the phenolic extract obtained from the sunflower seed cake as a retarder of the lipid oxidation reaction in soybean oil and to compare the results with a synthetic antioxidant. For this, the soybean oil, provided from the industry without any addition of antioxidants, was subjected to an accelerated storage test for 17 days at 65 °C. Six samples with different treatments were submitted to the test: control sample, without any addition of antioxidants; 100 ppm of synthetic antioxidant BHT; mixture of 50 ppm of BHT and 50 ppm of phenolic compounds; and 100, 500 and 1200 ppm of phenolic compounds. The phenolic compounds concentration in the extract was expressed in gallic acid equivalents. To evaluate the oxidative changes of the samples, aliquots were collected after 0, 3, 6, 10 and 17 days and analyzed for the peroxide, diene and triene conjugate values. The soybean oil sample initially had a peroxide content of 2.01 ± 0.27 meq of oxygen/kg of oil. On the third day of the treatment, only the samples treated with 100, 500 and 1200 ppm of phenolic compounds showed a considerable oxidation retard compared to the control sample. On the sixth day of the treatment, the samples presented a considerable increase in the peroxide value (higher than 13.57 meq/kg), and the higher the concentration of phenolic compounds, the lower the peroxide value verified. From the tenth day on, the samples had a very high peroxide value (higher than 55.39 meq/kg), where only the sample containing 1200 ppm of phenolic compounds presented significant oxidation retard. The samples containing the phenolic extract were more efficient to avoid the formation of the primary oxidation products, indicating effectiveness to retard the reaction. Similar results were observed for dienes and trienes. Based on the results, phenolic compounds, especially chlorogenic acid (the major phenolic compound of sunflower seed cake), can be considered as a potential partial or even total substitute for synthetic antioxidants.

Keywords: chlorogenic acid, natural antioxidant, vegetables oil deterioration, waste valorization

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Authors: Álvaro Ramírez Vidal, Martín Muñoz Morales, Francisco Jesús Fernández Morales, Luis Rodríguez Romero, José Villaseñor Camacho, Javier Llanos López

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In recent times, environmental problems have led to the extensive use of biological systems to solve them. Among the different types of biological systems, the use of plants such as aquatic macrophytes in constructed wetlands and terrestrial plant species for treating polluted soils and sludge has gained importance. Though the use of constructed wetlands for wastewater treatment is a well-researched domain, the slowness of pollutant degradation and high biomass production pose some challenges. Plants used in CW participate in different mechanisms for the capture and degradation of pollutants that also can retain some pharmaceutical and personal care products (PPCPs) that are very persistent in the environment. Thus, these systems present advantages in line with the guidelines published for the transition towards friendly and ecological procedures as they are environmentally friendly systems, consume low energy, or capture atmospheric CO₂. However, the use of CW presents some drawbacks, as the slowness of pollutant degradation or the production of important amounts of plant biomass, which need to be harvested and managed periodically. Taking this opportunity in mind, it is important to highlight that this residual biomass (of lignocellulosic nature) could be used as the feedstock for the generation of carbonaceous materials using thermochemical transformations such as slow pyrolysis or hydrothermal carbonization to produce high-value biomass-derived carbons through sustainable processes as adsorbents, catalysts…, thereby improving the circular carbon economy. Thus, this work carried out the analysis of some PPCPs commonly found in urban wastewater, as salicylic acid or ibuprofen, to evaluate the remediation carried out for the Phragmites Australis. Then, after the harvesting, this biomass can be used to synthesize electrodes through hydrothermal carbonization (HTC) and produce high-value biomass-derived carbons with electrocatalytic activity to remove heavy metals and persistent pollutants, promoting circular economy concepts. To do this, it was chosen biomass derived from the natural environment in high environmental risk as the Daimiel Wetlands National Park in the center of Spain, and the rest of the biomass developed in a CW specifically designed to remove pollutants. The research emphasizes the impact of the composition of the biomass waste and the synthetic parameters applied during HTC on the electrocatalytic activity. Additionally, this parameter can be related to the physicochemical properties, as porosity, surface functionalization, conductivity, and mass transfer of the electrodes lytic inks. Data revealed that carbon materials synthesized have good surface properties (good conductivities and high specific surface area) that enhance the electro-oxidants generated and promote the removal of PPCPs and the chemical oxygen demand of polluted waters.

Keywords: constructed wetlands, carbon materials, heavy metals, pharmaceutical and personal care products, hydrothermal carbonization

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Authors: Leo Nnamdi Ozurumba-Dwight

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Single-cell genomic analytical systems have proved to be a platform to isolate bulk cells into selected single cells for genomic, proteomic, and related metabolomic studies. This is enabling systematic investigations of the level of heterogeneity in a diverse and wide pool of cell populations. Single cell technologies, embracing techniques such as high parameter flow cytometry, single-cell sequencing, and high-resolution images are playing vital roles in these investigations on messenger ribonucleic acid (mRNA) molecules and related gene expressions in tracking the nature and course of disease conditions. This entails targeted molecular investigations on unit cells that help us understand cell behavoiur and expressions, which can be examined for their health implications on the health state of patients. One of the vital good sides of single-cell RNA sequencing (scRNA seq) is its probing capacity to detect deranged or abnormal cell populations present within homogenously perceived pooled cells, which would have evaded cursory screening on the pooled cell populations of biological samples obtained as part of diagnostic procedures. Despite conduction of just single-cell transcriptome analysis, scRNAseq now permits comparison of the transcriptome of the individual cells, which can be evaluated for gene expressional patterns that depict areas of heterogeneity with pharmaceutical drug discovery and clinical treatment applications. It is vital to strictly work through the tools of investigations from wet lab to bioinformatics and computational tooled analyses. In the precise steps for scRNAseq, it is critical to do thorough and effective isolation of viable single cells from the tissues of interest using dependable techniques (such as FACS) before proceeding to lysis, as this enhances the appropriate picking of quality mRNA molecules for subsequent sequencing (such as by the use of Polymerase Chain Reaction machine). Interestingly, scRNAseq can be deployed to analyze various types of biological samples such as embryos, nervous systems, tumour cells, stem cells, lymphocytes, and haematopoietic cells. In haematopoietic cells, it can be used to stratify acute myeloid leukemia patterns in patients, sorting them out into cohorts that enable re-modeling of treatment regimens based on stratified presentations. In immunotherapy, it can furnish specialist clinician-immunologist with tools to re-model treatment for each patient, an attribute of precision medicine. Finally, the good predictive attribute of scRNAseq can help reduce the cost of treatment for patients, thus attracting more patients who would have otherwise been discouraged from seeking quality clinical consultation help due to perceived high cost. This is a positive paradigm shift for patients’ attitudes primed towards seeking treatment.

Keywords: immunotherapy, transcriptome, re-modeling, mRNA, scRNA-seq

Procedia PDF Downloads 157

Authors: Mustapha A. Tijjani, Fanna I. Abdulrahman, Irfan Z. Khan, Umar K. Sandabe, Cong Li

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Air dried sample V. doniana after collection and identification was extracted with ethanol and further partition with chloroform, ethyl acetate and n-butanol. Ethanolic extract (11.9g) was fractionated on a silica gel accelerated column chromatography using solvents such as n-hexane, ethyl acetate and methanol. Each eluent fractions (150ml aliquots) were collected and monitored with thin layer chromatography. Fractions with similar Rf values from same solvents system were pooled together. Phytochemical test of all the fractions were performed using standard procedure. Complete elution yielded 48 fractions (150ml/fraction) which were pooled to 24 fractions base on the Rf values. It was further recombined and 12 fractions were obtained on the basis on Rf values and coded Vd1 to Vd12 fractions. Vd8 was further eluted with ethylacetate and methanol and gave fourteen sub fractions Vd8-a, -Vd8-m. Fraction Vd8-a (56mg) gave a white crystal compound coded V1. It was further checked on TLC and observed under ultraviolet lamp and was found to give a single spot. The Rf values were calculated to be 0.433. The melting point was determined using Gallenkamp capillary melting point apparatus and found to be 241-243°C uncorrected. Characterization of the isolated compound coded V1 was done using FT-infra-red spectroscopy, HNMR, 13CNMR(1and 2D) and HRESI-MS. The IR spectrum of compound V1 shows prominent peaks that corresponds to OHstr (3365cm-1) and C=0 (1652cm-1) etc. This spectrum suggests that among the functional moiety in compound V1 are the carbonyl and hydroxyl group. The 1H NMR (400 MHz) spectrum of compound V1 in DMSO-d6 displayed five singlet signals at δ 0.72 (3H, s, H-18), 0.79 (3H, s, H-19), 1.03 (3H, s, H-21), 1.04 (3H, s, H-26), 1.06 (3H, s, H-27) each integrating for three protons indicating the five methyl functional groups present in the compound. It further showed a broad singlet at δ 5.58 integrated for 1 H due to an olefinic H-atom adjacent to the carbonyl carbon atom. Three signals at δ 3.10 (d, J = 9.0 Hz, H-22), 3.59 (m, 1H, 2H-a) and 3.72 (m, 1H, 3H-e), each integrating for one proton is due to oxymethine protons indicating that three oxymethine H-atoms are present in the compound. These all signals are characteristic to the ecdysteroid skeletons. The 13C-NMR spectrum showed the presence of 27 carbon atoms, suggesting that may be steroid skeleton. The DEPT-135 experiment showed the presence of five CH3, eight CH2, and seven CH groups, and seven quaternary C-atoms. The molecular formula was established as C27H44O7 by high resolution electron spray ionization-mass spectroscopy (HRESI-MS) positive ion mode m/z 481.3179. The signals in mass spectrum are 463, 445, and 427 peaks corresponding to losses of one, two, three, or four water molecules characteristic for ecdysterone skeleton reported in the literature. Based on the spectral analysis (HNMR, 13CNMR, DEPT, HMQC, IR, HRESI-MS) the compound V1 is thus concluded to have ecdysteriod skeleton and conclusively conforms with 2β, 3β 14α, 20R, 22R, 25-hexahydroxy-5 β cholest-7-ene-6- one, or 2, 3, 14, 20, 22, 25 hexahydroxy cholest-7-ene-6-one commonly known as 20-hydroxyecdysone.

Keywords: vitex, phytochemical, purification, isolation, chromatography, spectroscopy

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Authors: Razieh Karimi Aghcheh, Christian Kubicek, Joseph Strauss, Gerhard Braus

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Filamentous fungi are of considerable economic and social significance for human health, nutrition and in white biotechnology. These organisms are dominant producers of a range of primary metabolites such as citric acid, microbial lipids (biodiesel) and higher unsaturated fatty acids (HUFAs). In particular, they produce also important but structurally complex secondary metabolites with enormous therapeutic applications in pharmaceutical industry, for example: cephalosporin, penicillin, taxol, zeranol and ergot alkaloids. Several fungal secondary metabolites, which are significantly relevant to human health do not only include antibiotics, but also e.g. lovastatin, a well-known antihypercholesterolemic agent produced by Aspergillus. terreus, or aflatoxin, a carcinogen produced by A. flavus. In addition to their roles for human health and agriculture, some fungi are industrially and commercially important: Species of the ascomycete genus Hypocrea spp. (teleomorph of Trichoderma) have been demonstrated as efficient producer of highly active cellulolytic enzymes. This trait makes them effective in disrupting and depolymerization of lignocellulosic materials and thus applicable tools in number of biotechnological areas as diverse as clothes-washing detergent, animal feed, and pulp and fuel productions. Fungal LaeA/LAE1 (Loss of aflR Expression A) homologs their gene products act at the interphase between secondary metabolisms, cellulase production and development. Lack of the corresponding genes results in significant physiological changes including loss of secondary metabolite and lignocellulose degrading enzymes production. At the molecular level, the encoded proteins are presumably methyltransferases or demethylases which act directly or indirectly at heterochromatin and interact with velvet domain proteins. Velvet proteins bind to DNA and affect expression of secondary metabolites (SMs) genes and cellulases. The dynamic interplay between LaeA/LAE1, velvet proteins and additional interaction partners is the key for an understanding of the coordination of metabolic and morphological functions of fungi and is required for a biotechnological control of the formation of desired bioactive products. Aspergilli and Trichoderma represent different biotechnologically significant species with significant differences in the LaeA/LAE1-Velvet protein machinery and their target proteins. We, therefore, performed a comparative study of the interaction partners of this machinery and the dynamics of the various protein-protein interactions using our robust proteomic and mass spectrometry techniques. This enhances our knowledge about the fungal coordination of secondary metabolism, cellulase production and development and thereby will certainly improve recombinant fungal strain construction for the production of industrial secondary metabolite or lignocellulose hydrolytic enzymes.

Keywords: cellulases, LaeA/1, proteomics, secondary metabolites

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Authors: E. Carraro, Sa. Bonetta, Si. Bonetta, E. Ceretti, G. C. V. Viola, C. Pignata, S. Levorato, T. Salvatori, S. Vannini, V. Romanazzi, A. Carducci, G. Donzelli, T. Schilirò, A. De Donno, T. Grassi, S. Bonizzoni, A. Bonetti, G. Gilli, U. Gelatti

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In 2013, air pollution and particulate matter were classified as carcinogenic to human by the IARC. At present, PM is Europe's most problematic pollutant in terms of harm to health, as reported by European Environmental Agency (EEA) in the EEA Technical Report on Air quality in Europe, 2015. A percentage between 17-30 of the EU urban population lives in areas where the EU air quality 24-hour limit value for PM10 is exceeded. Many studies have found a consistent association between exposure to PM and the incidence and mortality for some chronic diseases (i.e. lung cancer, cardiovascular diseases). Among the mechanisms responsible for these adverse effects, genotoxic damage is of particular concern. Children are a high-risk group in terms of the health effects of air pollution and early exposure during childhood can increase the risk of developing chronic diseases in adulthood. The MAPEC_LIFE (Monitoring Air Pollution Effects on Children for supporting public health policy) is a project founded by EU Life+ Programme (LIFE12 ENV/IT/000614) which intends to evaluate the associations between air pollution and early biological effects in children and to propose a model for estimating the global risk of early biological effects due to air pollutants and other factors in children. This work is focused on the micronuclei frequency in child buccal cells in association with airborne PM levels taking into account the influence of other factors associated with the lifestyle of children. The micronucleus test was performed in exfoliated buccal cells of 6–8 years old children from 5 Italian towns with different air pollution levels. Data on air quality during the study period were obtained from the Regional Agency for Environmental Protection. A questionnaire administered to children’s parents was used to obtain details on family socio-economic status, children health condition, exposures to other indoor and outdoor pollutants (i.e. passive smoke) and life-style, with particular reference to eating habits. During the first sampling campaign (winter 2014-15) 1315 children were recruited and sampled for Micronuclei test in buccal cells. In the sampling period the levels of the main pollutants and PM10 were, as expected, higher in the North of Italy (PM10 mean values 62 μg/m3 in Torino and 40 μg/m3 in Brescia) than in the other towns (Pisa, Perugia, Lecce). A higher Micronucleus frequency in buccal cells of children was found in Brescia (0.6/1000 cells) than in the other towns (range 0.3-0.5/1000 cells). The statistical analysis underlines a relation of the micronuclei frequency with PM concentrations, traffic level near child residence, and level of education of parents. The results suggest that, in addition to air pollution exposure, some other factors, related to lifestyle or further exposures, may influence micronucleus frequency and cellular response to air pollutants.

Keywords: air pollution, buccal cells, children, micronucleus cytome assay

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Authors: Naima Mohammadi

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The present paper critically reports on the emergency of Iranian international students in a large public university in Italy. Although the most sizeable diaspora of Iranians dates back to the 1979 revolution, a huge wave of Iranian female students travelled abroad after the Iranian Green Movement (2009) due to the intensification of gender discrimination and Islamization. To explore the experience of Iranian female students at an Italian public university, two complementary methods were adopted: a focus group and individual interviews. Focus groups yield detailed collective conversations and provide researchers with an opportunity to observe the interaction between participants, rather than between participant and researcher, which generates data. Semi-structured interviews allow participants to share their stories in their own words and speak about personal experiences and opinions. Research participants were invited to participate through a public call in a Telegram group of Iranian students. Theoretical and purposive sampling was applied to select participants. All participants were assured that full anonymity would be ensured and they consented to take part in the research. A two-hour focus group was held in English with participants in the presence and some online. They were asked to share their motivations for studying in Italy and talk about their experiences both within and outside the university context. Each of these interviews lasted from 45 to 60 minutes and was mostly carried out online and in Farsi. The focus group consisted of 8 Iranian female post-graduate students. In analyzing the data a blended approach was adopted, with a combination of deductive and inductive coding. According to research findings, although 9/11 was the beginning of the West’s challenges against Muslims, the nuclear threats of Islamic regimes promoted the toughest international sanctions against Iranians as a nation across the world. Accordingly, carrying an Iranian identity contributes to social, political, and economic exclusion. Research findings show that geopolitical factors such as international sanctions and Islamophobia, and a lack of reciprocity in terms of recognition, have created a sense of stigmatization for veiled and unveiled Iranian female students who are the largest groups of ‘non-European Muslim international students’ enrolled in Italian universities. Participants addressed how their nationality has devalued their public image and negatively impacted their self-confidence and self-realization in academia. They highlighted the experience of an unwelcoming atmosphere by different groups of people and institutes, such as receiving marked students’ badges, rejected bank account requests, failed visa processes, secondary security screening selection, and hyper-visibility of veiled students. This study corroborates the need for institutions to pay attention to geopolitical factors and religious diversity in student recruitment and provide support mechanisms and access to basic rights. Accordingly, it is suggested that Higher Education Institutions (HEIs) have a social and moral responsibility towards the discrimination and both social and academic exclusion of Iranian students.

Keywords: Iranian diaspora, female students, recognition theory, inclusive university

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Authors: Poojan Gharat, Haridas Pal, Sharmistha Dutta Choudhury

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Tuning photophysical properties of guest dyes through host-guest interactions involving macrocyclic hosts are the attractive research areas since past few decades, as these changes can directly be implemented in chemical sensing, molecular recognition, fluorescence imaging and dye laser applications. Excited state intramolecular proton transfer (ESIPT) is an intramolecular prototautomerization process display by some specific dyes. The process is quite amenable to tunability by the presence of different macrocyclic hosts. The present study explores the interesting effect of p-sulfonatocalix[n]arene (SCXn) and cyclodextrin (CD) hosts on the excited-state prototautomeric equilibrium of Chrysazine (CZ), a model antitumour drug. CZ exists exclusively in its normal form (N) in the ground state. However, in the excited state, the excited N* form undergoes ESIPT along with its pre-existing intramolecular hydrogen bonds, giving the excited state prototautomer (T*). Accordingly, CZ shows a single absorption band due to N form, but two emission bands due to N* and T* forms. Facile prototautomerization of CZ is considerably inhibited when the dye gets bound to SCXn hosts. However, in spite of lower binding affinity, the inhibition is more profound with SCX6 host as compared to SCX4 host. For CD-CZ system, while prototautomerization process is hindered by the presence of β-CD, it remains unaffected in the presence of γCD. Reduction in the prototautomerization process of CZ by SCXn and βCD hosts is unusual, because T* form is less dipolar in nature than the N*, hence binding of CZ within relatively hydrophobic hosts cavities should have enhanced the prototautomerization process. At the same time, considering the similar chemical nature of two CD hosts, their effect on prototautomerization process of CZ would have also been similar. The atypical effects on the prototautomerization process of CZ by the studied hosts are suggested to arise due to the partial inclusion or external binding of CZ with the hosts. As a result, there is a strong possibility of intermolecular H-bonding interaction between CZ dye and the functional groups present at the portals of SCXn and βCD hosts. Formation of these intermolecular H-bonds effectively causes the pre-existing intramolecular H-bonding network within CZ molecule to become weak, and this consequently reduces the prototautomerization process for the dye. Our results suggest that rather than the binding affinity between the dye and host, it is the orientation of CZ in the case of SCXn-CZ complexes and the binding stoichiometry in the case of CD-CZ complexes that play the predominant role in influencing the prototautomeric equilibrium of the dye CZ. In the case of SCXn-CZ complexes, the results obtained through experimental findings are well supported by quantum chemical calculations. Similarly for CD-CZ systems, binding stoichiometries obtained through geometry optimization studies on the complexes between CZ and CD hosts correlate nicely with the experimental results. Formation of βCD-CZ complexes with 1:1 stoichiometry while formation of γCD-CZ complexes with 1:1, 1:2 and 2:2 stoichiometries are revealed from geometry optimization studies and these results are in good accordance with the observed effects by the βCD and γCD hosts on the ESIPT process of CZ dye.

Keywords: intermolecular proton transfer, macrocyclic hosts, quantum chemical studies, photophysical studies

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Authors: Yazan S. Khaled, Shazana Shamsuddin, Jim Tiernan, Mike McPherson, Thomas Hughes, Paul Millner, David G. Jayne

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Introduction: There is a need for real-time imaging of colorectal cancer (CRC) to allow tailored surgery to the disease stage. Fluorescence guided laparoscopic imaging of primary colorectal cancer and the draining lymphatics would potentially bring stratified surgery into clinical practice and realign future CRC management to the needs of patients. Fluorescent nanoparticles can offer many advantages in terms of intra-operative imaging and therapy (theranostic) in comparison with traditional soluble reagents. Nanoparticles can be functionalised with diverse reagents and then targeted to the correct tissue using an antibody or Affimer (artificial binding protein). We aimed to develop and test fluorescent silica nanoparticles and targeted against CRC using an anti-carcinoembryonic antigen (CEA) Affimer (Aff). Methods: Anti-CEA and control Myoglobin Affimer binders were subcloned into the expressing vector pET11 followed by transformation into BL21 Star™ (DE3) E.coli. The expression of Affimer binders was induced using 0.1 mM isopropyl β-D-1-thiogalactopyranoside (IPTG). Cells were harvested, lysed and purified using nickle chelating affinity chromatography. The photosensitiser Foslip (soluble analogue of 5,10,15,20-Tetra(m-hydroxyphenyl) chlorin) was incorporated into the core of silica nanoparticles using water-in-oil microemulsion technique. Anti-CEA or control Affs were conjugated to silica nanoparticles surface using sulfosuccinimidyl-4-(N-maleimidomethyl) cyclohexane-1-carboxylate (sulfo SMCC) chemical linker. Binding of CEA-Aff or control nanoparticles to colorectal cancer cells (LoVo, LS174T and HC116) was quantified in vitro using confocal microscopy. Results: The molecular weights of the obtained band of Affimers were ~12.5KDa while the diameter of functionalised silica nanoparticles was ~80nm. CEA-Affimer targeted nanoparticles demonstrated 9.4, 5.8 and 2.5 fold greater fluorescence than control in, LoVo, LS174T and HCT116 cells respectively (p < 0.002) for the single slice analysis. A similar pattern of successful CEA-targeted fluorescence was observed in the maximum image projection analysis, with CEA-targeted nanoparticles demonstrating 4.1, 2.9 and 2.4 fold greater fluorescence than control particles in LoVo, LS174T, and HCT116 cells respectively (p < 0.0002). There was no significant difference in fluorescence for CEA-Affimer vs. CEA-Antibody targeted nanoparticles. Conclusion: We are the first to demonstrate that Foslip-doped silica nanoparticles conjugated to anti-CEA Affimers via SMCC allowed tumour cell-specific fluorescent targeting in vitro, and had shown sufficient promise to justify testing in an animal model of colorectal cancer. CEA-Affimer appears to be a suitable targeting molecule to replace CEA-Antibody. Targeted silica nanoparticles loaded with Foslip photosensitiser is now being optimised to drive photodynamic killing, via reactive oxygen generation.

Keywords: colorectal cancer, silica nanoparticles, Affimers, antibodies, imaging

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Authors: Reham Khalaf-Nazzal, Imad Dweikat, Paula Gimenez, Iker Oyenarte, Alfonso Martinez-Cruz, Domonik Muller

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Metal cation transport mediator (CNNM) gene family comprises 4 isoforms that are expressed in various human tissues. Structurally, CNNMs are complex proteins that contain an extracellular N-terminal domain preceding a DUF21 transmembrane domain, a ‘Bateman module’ and a C-terminal cNMP-binding domain. Mutations in CNNM2 cause familial dominant hypomagnesaemia. Growing evidence highlights the role of CNNM2 in neurodevelopment. Mutations in CNNM2 have been implicated in epilepsy, intellectual disability, schizophrenia, and others. In the present study, we aim to elucidate the function of CNNM2 in the developing brain. Thus, we present the genetic origin of symptoms in two family cohorts. In the first family, three siblings of a consanguineous Palestinian family in which parents are first cousins, and consanguinity ran over several generations, presented a varying degree of intellectual disability, cone-rod dystrophy, and autism spectrum disorder. Exome sequencing and segregation analysis revealed the presence of homozygous pathogenic mutation in the CNNM2 gene, the parents were heterozygous for that gene mutation. Magnesium blood levels were normal in the three children and their parents in several measurements. They had no symptoms of hypomagnesemia. The CNNM2 mutation in this family was found to locate in the CBS1 domain of the CNNM2 protein. The crystal structure of the mutated CNNM2 protein was not significantly different from the wild-type protein, and the binding of AMP or MgATP was not dramatically affected. This suggests that the CBS1 domain could be involved in pure neurodevelopmental functions independent of its magnesium-handling role, and this mutation could have affected a protein partner binding or other functions in this protein. In the second family, another autosomal dominant CNNM2 mutation was found to run in a large family with multiple individuals over three generations. All affected family members had hypomagnesemia and hypermagnesuria. Oral supplementation of magnesium did not increase the levels of magnesium in serum significantly. Some affected members of this family have defects in fine motor skills such as dyslexia and dyslalia. The detected mutation is located in the N-terminal part, which contains a signal peptide thought to be involved in the sorting and routing of the protein. In this project, we describe heterogenous clinical phenotypes related to CNNM2 mutations and protein functions. In the first family, and up to the authors’ knowledge, we report for the first time the involvement of CNNM2 in retinal photoreceptor development and function. In addition, we report the presence of a neurophenotype independent of magnesium status related to the CNNM2 protein mutation. Taking into account the different modes of inheritance and the different positions of the mutations within CNNM2 and its different structural and functional domains, it is likely that CNNM2 might be involved in a wide spectrum of neuropsychiatric comorbidities with considerable varying phenotypes.

Keywords: magnesium transport, autosomal recessive, autism, neurodevelopment, CBS domain

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Authors: Rhiannon Barker, Gregory Hartwell, Matt Egan, Karen Lock

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Background: Evidence suggests that mental health (MH) issues in children and young people (CYP) in the UK are on the rise. Of particular concern is data that indicates that the pandemic, together with the impact of school closures, have accentuated already pronounced inequalities; children from families on low incomes or from black and minority ethnic groups are reportedly more likely to have been adversely impacted. This study aimed to help identify specific support which may facilitate the building of a positive school climate and protect student mental health, particularly in the wake of school closures following the pandemic. It has important implications for integrated working between schools and statutory health services. Methods: The research comprised of three parts; scoping, case studies, and a stakeholder workshop to explore and consolidate results. The scoping phase included a literature review alongside interviews with a range of stakeholders from government, academia, and the third sector. Case studies were then conducted in two London state schools. Results: Our research identified how student MH was being impacted by a range of factors located at different system levels, both internal to the school and in the wider community. School climate, relating both to a shared system of beliefs and values, as well as broader factors including style of leadership, teaching, discipline, safety, and relationships -all played a role in the experience of school life and, consequently, the MH of both students and staff. Participants highlighted the importance of a whole school approach and ensuring that support for student MH was not separated from academic achievement, as well as the importance of identifying and applying universal measuring systems to establish levels of MH need. Our findings suggest that a school’s climate is influenced by the style and strength of its leadership, while this school climate - together with mechanisms put in place to respond to MH needs (both statutory and non-statutory) - plays a key role in supporting student MH. Implications: Schools in England have a responsibility to decide on the nature of MH support provided for their students, and there is no requirement for them to report centrally on the form this provision takes. The reality on the ground, as our study suggests, is that MH provision varies significantly between schools, particularly in relation to ‘lower’ levels of need which are not covered by statutory requirements. A valid concern may be that in the huge raft of possible options schools have to support CYP wellbeing, too much is left to chance. Work to support schools in rebuilding their cultures post-lockdowns must include the means to identify and promote appropriate tools and techniques to facilitate regular measurement of student MH. This will help establish both the scale of the problem and monitor the effectiveness of the response. A strong vision from a school’s leadership team that emphasises the importance of student wellbeing, running alongside (but not overshadowed by) academic attainment, should help shape a school climate to promote beneficial MH outcomes. The sector should also be provided with support to improve the consistency and efficacy of MH provision in schools across the country.

Keywords: mental health, schools, young people, whole-school culture

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