Search results for: synthetic dataset

Authors: Kostas Kouvaris, Anastasia Eleftheriou, Georgios A. Sarantitis, Apostolos Chondronasios

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To achieve the objective of almost zero carbon energy solutions by 2050, the EU needs to accelerate the development of integrated, highly efficient and environmentally friendly solutions. In this direction, district heating and cooling (DHC) emerges as a viable and more efficient alternative to conventional, decentralized heating and cooling systems, enabling a combination of more efficient renewable and competitive energy supplies. In this paper, we develop a forecasting tool for near real-time local weather and thermal energy demand predictions for an entire DHC network. In this fashion, we are able to extend the functionality and to improve the energy efficiency of the DHC network by predicting and adjusting the heat load that is distributed from the heat generation plant to the connected buildings by the heat pipe network. Two case-studies are considered; one for Vransko, Slovenia and one for Montpellier, France. The data consists of i) local weather data, such as humidity, temperature, and precipitation, ii) weather forecast data, such as the outdoor temperature and iii) DHC operational parameters, such as the mass flow rate, supply and return temperature. The external temperature is found to be the most important energy-related variable for space conditioning, and thus it is used as an external parameter for the energy demand models. For the development of the forecasting tool, we use state-of-the-art deep neural networks and more specifically, recurrent networks with long-short-term memory cells, which are able to capture complex non-linear relations among temporal variables. Firstly, we develop models to forecast outdoor temperatures for the next 24 hours using local weather data for each case-study. Subsequently, we develop models to forecast thermal demand for the same period, taking under consideration past energy demand values as well as the predicted temperature values from the weather forecasting models. The contributions to the scientific and industrial community are three-fold, and the empirical results are highly encouraging. First, we are able to predict future thermal demand levels for the two locations under consideration with minimal errors. Second, we examine the impact of the outdoor temperature on the predictive ability of the models and how the accuracy of the energy demand forecasts decreases with the forecast horizon. Third, we extend the relevant literature with a new dataset of thermal demand and examine the performance and applicability of machine learning techniques to solve real-world problems. Overall, the solution proposed in this paper is in accordance with EU targets, providing an automated smart energy management system, decreasing human errors and reducing excessive energy production.

Keywords: machine learning, LSTMs, district heating and cooling system, thermal demand

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Authors: Hasan Demiroğlu, Uğur Avcıbaşı, Serhan Sakarya, Perihan Ünak

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Implanted devices are progressively practiced in innovative medicine to relieve pain or improve a compromised function. Implant-associated infections represent an emerging complication, caused by organisms which adhere to the implant surface and grow embedded in a protective extracellular polymeric matrix, known as a biofilm. In addition, the microorganisms within biofilms enter a stationary growth phase and become phenotypically resistant to most antimicrobials, frequently causing treatment failure. In such cases, surgical removal of the implant is often required, causing high morbidity and substantial healthcare costs. Staphylococcus aureus is the most common pathogen causing implant-associated infections. Successful treatment of these infections includes early surgical intervention and antimicrobial treatment with bactericidal drugs that also act on the surface-adhering microorganisms. Linezolid is a promising anti-microbial with ant-staphylococcal activity, used for the treatment of MRSA infections. Linezolid is a synthetic antimicrobial and member of oxazolidinoni group, with a bacteriostatic or bactericidal dose-dependent antimicrobial mechanism against gram-positive bacteria. Intensive use of antibiotics, have emerged multi-resistant organisms over the years and major problems have begun to be experienced in the treatment of infections occurred with them. While new drugs have been developed worldwide, on the other hand infections formed with microorganisms which gained resistance against these drugs were reported and the scale of the problem increases gradually. Scientific studies about the production of bacterial biofilm increased in recent years. For this purpose, we investigated the activity of Lin, Lin radiolabeled with 131I (131I-Lin) and cold iodinated Lin (127I-Lin) against clinical strains of Staphylococcus aureus DSM 4910 in biofilm. In the first stage, radio and cold labeling studies were performed. Quality-control studies of Lin and iodo (radio and cold) Lin derivatives were carried out by using TLC (Thin Layer Radiochromatography) and HPLC (High Pressure Liquid Chromatography). In this context, it was found that the binding yield was obtained to be about 86±2 % for 131I-Lin. The minimal inhibitory concentration (MIC) of Lin, 127I-Lin and 131I-Lin for Staphylococcus aureus DSM 4910 strain were found to be 1µg/mL. In time-kill studies of Lin, 127I-Lin and 131I-Lin were producing ≥ 3 log10 decreases in viable counts (cfu/ml) within 6 h at 2 and 4 fold of MIC respectively. No viable bacteria were observed within the 24 h of the experiments. Biofilm eradication of S. aureus started with 64 µg/mL of Lin, 127I-Lin and 131I-Lin, and OD630 was 0.507±0.0.092, 0.589±0.058 and 0.266±0.047, respectively. The media control of biofilm producing Staphylococcus was 1.675±0,01 (OD630). 131I and 127I did not have any effects on biofilms. Lin and 127I-Lin were found less effectively than 131I-Lin at killing cells in biofilm and biofilm eradication. Our results demonstrate that the 131I-Lin have potent anti-biofilm activity against S. aureus compare to Lin, 127I-Lin and media control. This is suggested that, 131I may have harmful effect on biofilm structure.

Keywords: iodine-131, linezolid, radiolabeling, slime layer, Staphylococcus

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Authors: Lijuan Li

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Nitric oxide (NO) has become a fascinating entity in biological chemistry over the past few years. It is a gaseous lipophilic radical molecule that plays important roles in several physiological and pathophysiological processes in mammals, including activating the immune response, serving as a neurotransmitter, regulating the cardiovascular system, and acting as an endothelium-derived relaxing factor. NO functions in eukaryotes both as a signal molecule at nanomolar concentrations and as a cytotoxic agent at micromolar concentrations. The latter arises from the ability of NO to react readily with a variety of cellular targets leading to thiol S-nitrosation, amino acid N-nitrosation, and nitrosative DNA damage. Nitric oxide can readily bind to metals to give metal-nitrosyl (M-NO) complexes. Some of these species are known to play roles in biological NO storage and transport. These complexes have different biological, photochemical, or spectroscopic properties due to distinctive structural features. These recent discoveries have spawned a great interest in the development of transition metal complexes containing NO, particularly its iron complexes that are central to the role of nitric oxide in the body. Spectroscopic evidence would appear to implicate species of “Fe(NO)2+” type in a variety of processes ranging from polymerization, carcinogenesis, to nitric oxide stores. Our research focuses on isolation and structural studies of non-heme iron nitrosyls that mimic biologically active compounds and can potentially be used for anticancer drug therapy. We have shown that reactions between Fe(NO)2(CO)2 and a series of imidazoles generated new non-heme iron nitrosyls of the form Fe(NO)2(L)2 [L = imidazole, 1-methylimidazole, 4-methylimidazole, benzimidazole, 5,6-dimethylbenzimidazole, and L-histidine] and a tetrameric cluster of [Fe(NO)2(L)]4 (L=Im, 4-MeIm, BzIm, and Me2BzIm), resulted from the interactions of Fe(NO)2 with a series of substituted imidazoles was prepared. Recently, a series of sulfur bridged iron di nitrosyl complexes with the general formula of [Fe(µ-RS)(NO)2]2 (R = n-Pr, t-Bu, 6-methyl-2-pyridyl, and 4,6-dimethyl-2-pyrimidyl), were synthesized by the reaction of Fe(NO)2(CO)2 with thiols or thiolates. Their structures and properties were studied by IR, UV-vis, 1H-NMR, EPR, electrochemistry, X-ray diffraction analysis and DFT calculations. IR spectra of these complexes display one weak and two strong NO stretching frequencies (νNO) in solution, but only two strong νNO in solid. DFT calculations suggest that two spatial isomers of these complexes bear 3 Kcal energy difference in solution. The paramagnetic complexes [Fe2(µ-RS)2(NO)4]-, have also been investigated by EPR spectroscopy. Interestingly, the EPR spectra of complexes exhibit an isotropic signal of g = 1.998 - 2.004 without hyperfine splitting. The observations are consistent with the results of calculations, which reveal that the unpaired electron dominantly delocalize over the two sulfur and two iron atoms. The difference of the g values between the reduced form of iron-sulfur clusters and the typical monomeric di nitrosyl iron complexes is explained, for the first time, by of the difference in unpaired electron distributions between the two types of complexes, which provides the theoretical basis for the use of g value as a spectroscopic tool to differentiate these biologically active complexes.

Keywords: di nitrosyl iron complex, metal nitrosyl, non-heme iron, nitric oxide

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Authors: Prescilla Lambert, Christophe Roos, Mounim Lebrini

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For several years, the Caribbean islands and West Africa have had to deal with the massive arrival of the brown seaweed Sargassum. Overall, this macroalgae, which constitutes a habitat for a great diversity of marine organisms, is also an additional stress factor for the marine environment (e.g., coral reefs). In addition, the accumulation followed by the significant decomposition of the Sargassum spp. biomass on the coast leads to the release of toxic gases (H₂S and NH₃), which calls into question the functioning of the economic, health and tourist life of the island and the other interested territories. Originally, these algae are formed by the eutrophication of the oceans accentuated by global warming. Unfortunately, scientists predict a significant recurrence of these Sargassum strandings for years to come. It is therefore more than necessary to find solutions by putting in place a sustainable management plan for this phenomenon. Martinique, a small island in the Caribbean arc, is one of the many areas impacted by Sargassum seaweed strandings. Since 2011, there has been a constant increase in the degradation of the materials present in this region, largely due to toxic/corrosive gases released by the algae decomposition. In order to protect the structures and the vulnerable building materials while limiting the use of synthetic/petroleum based molecules as much as possible, research is being conducted on molecules of natural origin. Thus, thanks to the chemical composition, which comprise molecules with interesting properties, algae such as Sargassum could potentially help to solve many issues. Therefore, this study focuses on the green extraction and characterization of molecules from the species Sargassum fluitans and Sargassum natans present in Martinique. The secondary metabolites found in these extracts showed variability in yield rates due to local climatic conditions. The tests carried out shed light on the anticorrosive and antibacterial potential of the algae. These extracts can thus be described as natural inhibitors. The effect of variation in inhibitor concentrations was tested in electrochemistry using electrochemical impedance spectroscopy and polarization curves. The analysis of electrochemical results obtained by direct immersion in the extracts and self-assembled molecular layers (SAMs) for Sargassum fluitans III, Sargassum natans I and VIII species was conclusive in acid and alkaline environments. The excellent results obtained reveal an inhibitory efficacy of 88% at 50mg/L for the crude extract of Sargassum fluitans III and efficacies greater than 97% for the chemical families of Sargassum fluitans III. Similarly, microbiological tests also suggest a bactericidal character. Results for Sargassum fluitans III crude extract show a minimum inhibitory concentration (MIC) of 0.005 mg/mL on Gram-negative bacteria and a MIC greater than 0.6 mg/mL on Gram-positive bacteria. These results make it possible to consider the management of local and international issues while valuing a biomass rich in biodegradable molecules. The next step in this study will therefore be the evaluation of the toxicity of Sargassum spp..

Keywords: Sargassum, secondary metabolites, anticorrosive, antibacterial, natural inhibitors

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Authors: Vladimir Berezin, Aizhan Turmagambetova, Andrey Bogoyavlenskiy, Pavel Alexyuk, Madina Alexyuk, Irina Zaitceva, Nadezhda Sokolova

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Introduction: Influenza viruses could infect approximately 5% to 10% of the global human population annually, resulting in serious social and economic damage. Vaccination and etiotropic antiviral drugs are used for the prevention and treatment of influenza. Vaccination is important; however, antiviral drugs represent the second line of defense against new emerging influenza virus strains for which vaccines may be unsuccessful. However, the significant drawback of commercial synthetic anti-flu drugs is the appearance of drug-resistant influenza virus strains. Therefore, the search and development of new anti-flu drugs efficient against drug-resistant strains is an important medical problem for today. The aim of this work was a study of four phenolic acids of plant origin (Gallic, Syringic, Vanillic, and Protocatechuic acids) as a possible tool for treatment against influenza virus. Methods: Phenolic acids; gallic, syringic, vanillic, and protocatechuic have been prepared by extraction from plant tissues and purified using high-performance liquid chromatography fractionation. Avian influenza virus, strain A/Tern/South Africa/1/1961 (H5N3) and human epidemic influenza virus, strain A/Almaty/8/98 (H3N2) resistant to commercial anti-flu drugs (Rimantadine, Oseltamivir) were used for testing antiviral activity. Viruses were grown in the allantoic cavity of 10 days old chicken embryos. The chemotherapeutic index (CTI), determined as the ratio of an average toxic concentration of the tested compound (TC₅₀) to the average effective virus-inhibition concentration (EC₅₀), has been used as a criteria of specific antiviral action. Results: The results of study have shown that the structure of phenolic acids significantly affected their ability to suppress the reproduction of tested influenza virus strains. The highest antiviral activity among tested phenolic acids was detected for gallic acid, which contains three hydroxyl groups in the molecule at C3, C4, and C5 positions. Antiviral activity of gallic acid against A/H5N3 and A/H3N2 influenza virus strains was higher than antiviral activity of Oseltamivir and Rimantadine. gallic acid inhibited almost 100% of the infection activity of both tested viruses. Protocatechuic acid, which possesses 2 hydroxyl groups (C3 and C4) have shown weaker antiviral activity in comparison with gallic acid and inhibited less than 10% of virus infection activity. Syringic acid, which contains two hydroxyl groups (C3 and C5), was able to suppress up to 12% of infection activity. Substitution of two hydroxyl groups by methoxy groups resulted in the complete loss of antiviral activity. Vanillic acid, which is different from protocatechuic acid by replacing of C3 hydroxyl group to methoxy group, was able to suppress about 30% of infection activity of tested influenza viruses. Conclusion: For pronounced antiviral activity, the molecular of phenolic acid must have at least two hydroxyl groups. Replacement of hydroxyl groups to methoxy group leads to a reduction of antiviral properties. Gallic acid demonstrated high antiviral activity against influenza viruses, including Rimantadine and Oseltamivir resistant strains, and could be used as a potential candidate for the development of antiviral drug against influenza virus.

Keywords: antiviral activity, influenza virus, drug resistance, phenolic acids

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Authors: Nino Kupatadze, Mzevinar Bedinashvili, Tamar Memanishvili, Manana Gurielidze, David Tugushi, Ramaz Katsarava

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Bacteria easily colonize the surfaces of tissues, surgical devices (implants, orthopedics, catheters, etc.), and instruments causing surgical device related infections. Therefore, the battle against bacteria and the prevention of surgical devices from biofilm formation is one of the main challenges of biomedicine today. Our strategy to the solution of this problem consists in using antimicrobial polymeric coatings as effective “shields” to protect surfaces from bacteria’s colonization and biofilm formation. As one of the most promising approaches look be the use of antimicrobial bioerodible polymeric nanocomposites containing silver nanoparticles (AgNPs). We assume that the combination of an erodible polymer with a strong bactericide should put obstacles to bacteria to occupy the surface and to form biofilm. It has to be noted that this kind of nanocomposites are also promising as wound dressing materials to treat infected superficial wounds. Various synthetic and natural polymers were used for creating biocomposites containing AgNPs as both particles' stabilizers and matrices forming elastic films at surfaces. One of the most effective systems to fabricate AgNPs is an ethanol solution of polyvinylpyrrolidone(PVP) with dissolved AgNO3–ethanol serves as a AgNO3 reductant and PVP as AgNPs stabilizer (through the interaction of nanoparticles with nitrogen atom of the amide group). Though PVP is biocompatible and film-forming polymer, it is not a good candidate to design either "biofilm shield" or wound dressing material because of a high solubility in water – though the solubility of PVP provides the desirable release of AgNPs from the matrix, but the coating is easily washable away from the surfaces. More promising as matrices look water insoluble but bioerodible polymers that can provide the release of AgNPs and form long-lasting coatings at the surfaces. For creating bioerodible water-insoluble antimicrobial coatings containing AgNPs, we selected amino acid based biodegradable polymers(AABBPs)–poly(ester amide)s, poly(ester urea)s, their copolymers containing amide and related groups capable to stabilize AgNPs. Among a huge variety of AABBPs reported we selected the polymers soluble in ethanol. For preparing AgNPs containing nanocompositions AABBPs and AgNO3 were dissolved in ethanol and subjected to photochemical reduction using daylight-irradiation. The formation of AgNPs was observed visually by coloring the solutions in brownish-red. The obtained AgNPs were characterized by UV-spectroscopy, transmission electron microscopy(TEM), and dynamic light scattering(DLS). According to the UV and TEM data, the photochemical reduction resulted presumably in spherical AgNPs with rather high contribution of the particles below 10 nm that are known as responsible for the antimicrobial activity. DLS study showed that average size of nanoparticles formed after photo-reduction in ethanol solution ranged within 50 nm. The in vitro antimicrobial activity study of the new nanocomposite material is in progress now.

Keywords: nanocomposites, silver nanoparticles, polymer, biodegradable

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Authors: D. Malouch, M. Berchel, C. Dreanno, S. Stachowski-Haberkorn, P-A. Jaffres

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Biofouling is a complex natural phenomenon that involves biological, physical and chemical properties related to the environment, the submerged surface and the living organisms involved. Bio-colonization of artificial structures can cause various economic and environmental impacts. The increase in costs associated with the over-consumption of fuel from biocolonized vessels has been widely studied. Measurement drifts from submerged sensors, as well as obstructions in heat exchangers, and deterioration of offshore structures are major difficulties that industries are dealing with. Therefore, surfaces that inhibit biocolonization are required in different areas (water treatment, marine paints, etc.) and many efforts have been devoted to produce efficient and eco-compatible antifouling agents. The different steps of surface fouling are widely described in literature. Studying the biofilm and its stages provides a better understanding of how to elaborate more efficient antifouling strategies. Several approaches are currently applied, such as the use of biocide anti-fouling paint (mainly with copper derivatives) and super-hydrophobic coatings. While these two processes are proving to be the most effective, they are not entirely satisfactory, especially in a context of a changing legislation. Nowadays, the challenge is to prevent biofouling with non-biocide compounds, offering a cost effective solution, but with no toxic effects on marine organisms. Since the micro-fouling phase plays an important role in the regulation of the following steps of biofilm formation, it is desired to reduce or delate biofouling of a given surface by inhibiting the micro-fouling at its early stages. In our recent works, we reported that some amphiphilic compounds exhibited bacteriostatic or bactericidal properties at a concentration that did not affect mammalian eukaryotic cells. These remarkable properties invited us to assess this type of bio-inspired phospholipids to prevent the colonization of surfaces by marine bacteria. Of note, other studies reported that amphiphilic compounds interacted with bacteria leading to a reduction of their development. An amphiphilic compound is a molecule consisting of a hydrophobic domain and a polar head (ionic or non-ionic). These compounds appear to have interesting antifouling properties: some ionic compounds have shown antimicrobial activity, and zwitterions can reduce nonspecific adsorption of proteins. Herein, we investigate the potential of amphiphilic compounds as inhibitors of bacterial growth and marine biofilm formation. The aim of this study is to compare the efficacy of four synthetic phospholipids that features a cationic charge or a zwitterionic polar-head group to prevent microfouling with marine bacteria. Toxicity of these compounds was also studied in order to identify the most promising compounds that inhibit biofilm development and show low cytotoxicity on two links representative of coastal marine food webs: phytoplankton and oyster larvae.

Keywords: amphiphilic phospholipids, biofilm, marine fouling, non-toxique assays

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Authors: Laura Roe

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This study draws on twelve months of ethnographic fieldwork conducted in 2017 with heroin and poly-substance users in Scotland and explores experiences of time and temporality as factors in continuing drug use. The research largely took place over the year in which drug-related deaths in Scotland reached a record high, and were statistically recorded as the highest in Europe. This qualitative research is therefore significant in understanding both evolving patterns of drug use and the experiential lifeworlds of those who use heroin and other substances in high doses. Methodologies included participant observation, structured and semi-structured interviews, and unstructured conversations with twenty-two regular participants. The fieldwork was conducted in two needle exchanges, a community recovery group and in the community. The initial aim of the study was to assess evolving patterns of drug preferences in order to explore a clinical and user-reported rise in the use of novel psychoactive substances (NPS), which are typically considered to be highly potent, synthetic substances, often available at a low cost. It was found, however, that while most research participants had experimented with NPS with varying intensity, those who used every day regularly consumed heroin, methadone, and alcohol with benzodiazepines such as diazepam or anticonvulsants such as gabapentin. The research found that many participants deliberately pursued the non-fatal effects of overdose, aiming to induce states of dissociation, detachment and uneven consciousness, and did so by both mixing substances and experimenting with novel modes of consumption. Temporality was significant in the decision to consume cocktails of substances, as users described wishing to sever themselves from time; entering into states of ‘non-time’ and insensibility through specific modes of intoxication. Time and temporality similarly impacted other aspects of addicted life. Periods of attempted abstinence witnessed a slowing of time’s passage that was tied to affective states of boredom and melancholy, in addition to a disruptive return of distressing and difficult memories. Abject past memories frequently dominated and disrupted the present, which otherwise could be highly immersive due to the time and energy-consuming nature of seeking drugs while in financial difficulty. There was furthermore a discordance between individual user temporalities and the strict time-based regimes of recovery services and institutional bodies, and the study aims to highlight the impact of such a disjuncture on the efficacy of treatment programs. Many participants had difficulty in adhering to set appointments or temporal frameworks due to their specific temporal situatedness. Overall, exploring increasing tendencies of heroin users in Scotland towards poly-substance use, this study draws on experiences and perceptions of time, analysing how temporality comes to bear on the ways drugs are sought and consumed, and how recovery is imagined and enacted. The study attempts to outline the experiential, intimate and subjective worlds of heroin and poly-substance users while explicating the structural and historical factors that shape them.

Keywords: addiction, poly-substance use, temporality, timelessness

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Authors: Richard Abel

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In the United States, increased incarceration rates have caused many adolescents to feel the strain of parental absence. This absence is then manifest through adolescent feelings of parental rejection. Additionally, upon reentry maternal incarceration may be related to adolescents experienced perceived excessive disciple. It is possible parents engage in this manner of discipline attempting to prevent the child from taking the same path to incarceration as the parent. According to General Strain Theory, adolescents encountering strain are likely to experience negative emotions. The emotion that is most likely to lead to delinquency is anger through reduced inhibitions and motivation to act. Additionally, males are more likely to engage in delinquent behavior, regardless of experiencing strain. This is not the case for every male who experiences maternal incarceration, parental rejection, excessive discipline, or anger. There are protective factors that enable agency within individuals. One such protective factor is mastery, or the perception that one is in control of his or her own future. The model proposed in this research suggests maternal incarceration is associated with increased parental rejection and excessive discipline in males. Males experiencing parental rejection and excessive discipline are likely to experience increased anger, which is then associated with increases in delinquent behavior. This model explores whether agency, in the form of mastery, mediates the relationship between strains and negative emotions, or between negative emotions and delinquent behavior. The Kaplan Longitudinal and Multigenerational Study (KLAMS) dataset is uniquely situated to analyze this model providing longitudinal data collected from both parents and their offspring. Maternal incarceration is constructed using parental responses such that the mother was incarcerated after the child’s birth, and any incarceration that happened prior to birth is excluded. The remaining variables of the study are all constructed from varying waves of the adolescent survey. Parental rejection, along with control variables for age, race, parental socioeconomic status, neighborhood effects, delinquent peers, and prior delinquent behavior are all constructed using Wave I data. To increase causal inference, the negative emotion of anger and the mediating variable of mastery are measured during Wave II. Lastly, delinquent behavior is measured at Wave III. Results of the analysis show expected relationships such that adolescent males encountering maternal incarceration show increased perception of parental rejection and excessive discipline. Additionally, there is a positive relationship between parental rejection and excessive discipline at Wave I and feelings of anger at Wave II for males. For males experiencing either of these strains in Wave I, feelings of anger in Wave II are found to be associated with increased delinquent behavior in Wave III. Mastery was found to mediate the relationship between both parental rejection and excessive discipline and anger, but no such mediation occurs in the relationship between anger and delinquency, regardless of the strain being experienced. These findings suggest adolescent males who feel they are in control of their own lives are less likely to experience negative emotions produced by the occurrence of strain, thereby decreasing male engagement in delinquent behavior later in life.

Keywords: delinquency, mastery, maternal incarceration, strain

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Authors: Amarendar Reddy Addula

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Definition of Artificial Intelligence: Artificial intelligence is the simulation of mortal intelligence processes by machines, especially computer systems. Explicit operations of AI comprise expert systems, natural language processing, and speech recognition, and machine vision. Artificial Intelligence (AI) is an original medium for digital business, according to a new report by Gartner. The last 10 times represent an advance period in AI’s development, prodded by the confluence of factors, including the rise of big data, advancements in cipher structure, new machine literacy ways, the materialization of pall computing, and the vibrant open- source ecosystem. Influence of AI to a broader set of use cases and druggies and its gaining fashionability because it improves AI’s versatility, effectiveness, and rigidity. Edge AI will enable digital moments by employing AI for real- time analytics closer to data sources. Gartner predicts that by 2025, further than 50 of all data analysis by deep neural networks will do at the edge, over from lower than 10 in 2021. Responsible AI is a marquee term for making suitable business and ethical choices when espousing AI. It requires considering business and societal value, threat, trust, translucency, fairness, bias mitigation, explainability, responsibility, safety, sequestration, and nonsupervisory compliance. Responsible AI is ever more significant amidst growing nonsupervisory oversight, consumer prospects, and rising sustainability pretensions. Generative AI is the use of AI to induce new vestiges and produce innovative products. To date, generative AI sweats have concentrated on creating media content similar as photorealistic images of people and effects, but it can also be used for law generation, creating synthetic irregular data, and designing medicinals and accoutrements with specific parcels. AI is the subject of a wide- ranging debate in which there's a growing concern about its ethical and legal aspects. Constantly, the two are varied and nonplussed despite being different issues and areas of knowledge. The ethical debate raises two main problems the first, abstract, relates to the idea and content of ethics; the alternate, functional, and concerns its relationship with the law. Both set up models of social geste, but they're different in compass and nature. The juridical analysis is grounded on anon-formalistic scientific methodology. This means that it's essential to consider the nature and characteristics of the AI as a primary step to the description of its legal paradigm. In this regard, there are two main issues the relationship between artificial and mortal intelligence and the question of the unitary or different nature of the AI. From that theoretical and practical base, the study of the legal system is carried out by examining its foundations, the governance model, and the nonsupervisory bases. According to this analysis, throughout the work and in the conclusions, International Law is linked as the top legal frame for the regulation of AI.

Keywords: artificial intelligence, ethics & human rights issues, laws, international laws

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Authors: Sara Rejeb, Catherine Duveau, Tabea Rebafka

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To monitor the production process of turbofan aircraft engines, multiple measurements of various geometrical parameters are systematically recorded on manufactured parts. Engine parts are subject to extremely high standards as they can impact the performance of the engine. Therefore, it is essential to analyze these databases to better understand the influence of the different parameters on the engine's performance. Self-organizing maps are unsupervised neural networks which achieve two tasks simultaneously: they visualize high-dimensional data by projection onto a 2-dimensional map and provide clustering of the data. This technique has become very popular for data exploration since it provides easily interpretable results and a meaningful global view of the data. As such, self-organizing maps are usually applied to aircraft engine condition monitoring. As databases in this field are huge and complex, they naturally contain multiple missing entries for various reasons. The classical Kohonen algorithm to compute self-organizing maps is conceived for complete data only. A naive approach to deal with partially observed data consists in deleting items or variables with missing entries. However, this requires a sufficient number of complete individuals to be fairly representative of the population; otherwise, deletion leads to a considerable loss of information. Moreover, deletion can also induce bias in the analysis results. Alternatively, one can first apply a common imputation method to create a complete dataset and then apply the Kohonen algorithm. However, the choice of the imputation method may have a strong impact on the resulting self-organizing map. Our approach is to address simultaneously the two problems of computing a self-organizing map and imputing missing values, as these tasks are not independent. In this work, we propose an extension of self-organizing maps for partially observed data, referred to as missSOM. First, we introduce a criterion to be optimized, that aims at defining simultaneously the best self-organizing map and the best imputations for the missing entries. As such, missSOM is also an imputation method for missing values. To minimize the criterion, we propose an iterative algorithm that alternates the learning of a self-organizing map and the imputation of missing values. Moreover, we develop an accelerated version of the algorithm by entwining the iterations of the Kohonen algorithm with the updates of the imputed values. This method is efficiently implemented in R and will soon be released on CRAN. Compared to the standard Kohonen algorithm, it does not come with any additional cost in terms of computing time. Numerical experiments illustrate that missSOM performs well in terms of both clustering and imputation compared to the state of the art. In particular, it turns out that missSOM is robust to the missingness mechanism, which is in contrast to many imputation methods that are appropriate for only a single mechanism. This is an important property of missSOM as, in practice, the missingness mechanism is often unknown. An application to measurements on one type of part is also provided and shows the practical interest of missSOM.

Keywords: imputation method of missing data, partially observed data, robustness to missingness mechanism, self-organizing maps

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Authors: B. Godefroy, D. Beladjine, K. Beddiar

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In France, construction BIM actors commonly evoke the BIM gains for exploitation by integrating of the life cycle of a building. The standardization of level 7 of development would achieve this stage of the digital model. The householders include local public authorities, social landlords, public institutions (health and education), enterprises, facilities management companies. They have a dual role: owner and manager of their housing complex. In a context of financial constraint, the BIM of exploitation aims to control costs, make long-term investment choices, renew the portfolio and enable environmental standards to be met. It assumes a knowledge of the existing buildings, marked by its size and complexity. The information sought must be synthetic and structured, it concerns, in general, a real estate complex. We conducted a study with professionals about their concerns and ways to use it to see how householders could benefit from this development. To obtain results, we had in mind the recurring interrogation of the project management, on the needs of the operators, we tested the following stages: 1) Inculcate a minimal culture of BIM with multidisciplinary teams of the operator then by business, 2) Learn by BIM tools, the adaptation of their trade in operations, 3) Understand the place and creation of a graphic and technical database management system, determine the components of its library so their needs, 4) Identify the cross-functional interventions of its managers by business (operations, technical, information system, purchasing and legal aspects), 5) Set an internal protocol and define the BIM impact in their digital strategy. In addition, continuity of management by the integration of construction models in the operation phase raises the question of interoperability in the control of the production of IFC files in the operator’s proprietary format and the export and import processes, a solution rivaled by the traditional method of vectorization of paper plans. Companies that digitize housing complex and those in FM produce a file IFC, directly, according to their needs without recourse to the model of construction, they produce models business for the exploitation. They standardize components, equipment that are useful for coding. We observed the consequences resulting from the use of the BIM in the property industry and, made the following observations: a) The value of data prevail over the graphics, 3D is little used b) The owner must, through his organization, promote the feedback of technical management information during the design phase c) The operator's reflection on outsourcing concerns the acquisition of its information system and these services, observing the risks and costs related to their internal or external developments. This study allows us to highlight: i) The need for an internal organization of operators prior to a response to the construction management ii) The evolution towards automated methods for creating models dedicated to the exploitation, a specialization would be required iii) A review of the communication of the project management, management continuity not articulating around his building model, it must take into account the environment of the operator and reflect on its scope of action.

Keywords: information system, interoperability, models for exploitation, property industry

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Authors: Farnaz Alborzi, Angelika Schmitz, Rainer Stamminger

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Reducing water temperatures in the wash phase of a washing programme and increasing the overall cycle durations are the latest trends in decreasing energy consumption of washing programmes. Since the implementation of the new energy efficiency classes in 2010, manufacturers seem to apply the aforementioned washing strategy with lower temperatures combined with longer programme durations extensively to realise energy-savings needed to meet the requirements of the highest energy efficiency class possible. A semi-representative on-line survey in eleven European countries (Czech Republic, Finland, France, Germany, Hungary, Italy, Poland, Romania, Spain, Sweden and the United Kingdom) was conducted by Bonn University in 2015 to shed light on consumer opinion and behaviour regarding the effects of the lower washing temperature and longer cycle duration in laundry washing on consumers’ acceptance of the programme. The risk of the long wash cycle is that consumers might not use the energy efficient Standard programmes and will think of this option as inconvenient and therefore switch to shorter, but more energy consuming programmes. Furthermore, washing in a lower temperature may lead to the problem of cross-contamination. Washing behaviour of over 5,000 households was studied in this survey to provide support and guidance for manufacturers and policy designers. Qualified households were chosen following a predefined quota: -Involvement in laundry washing: substantial, -Distribution of gender: more than 50 % female , -Selected age groups: -20–39 years, -40–59 years, -60–74 years, -Household size: 1, 2, 3, 4 and more than 4 people. Furthermore, Eurostat data for each country were used to calculate the population distribution in the respective age class and household size as quotas for the consumer survey distribution in each country. Before starting the analyses, the validity of each dataset was controlled with the aid of control questions. After excluding the outlier data, the number of the panel diminished from 5,100 to 4,843. The primary outcome of the study is European consumers are willing to save water and energy in a laundry washing but reluctant to use long programme cycles since they don’t believe that the long cycles could be energy-saving. However, the results of our survey don’t confirm that there is a relation between frequency of using Standard cotton (Eco) or Energy-saving programmes and the duration of the programmes. It might be explained by the fact that the majority of washing programmes used by consumers do not take so long, perhaps consumers just choose some additional time reduction option when selecting those programmes and this finding might be changed if the Energy-saving programmes take longer. Therefore, it may be assumed that introducing the programme duration as a new measure on a revised energy label would strongly influence the consumer at the point of sale. Furthermore, results of the survey confirm that consumers are more willing to use lower temperature programmes in order to save energy than accepting longer programme cycles and majority of them accept deviation from the nominal temperature of the programme as long as the results are good.

Keywords: duration, energy-saving, standard programmes, washing temperature

Procedia PDF Downloads 220

Authors: Noura Al Akkari, Aurélie Foucquier, Sylvain Lespinats

Abstract:

Load monitoring is a management process for energy consumption towards energy savings and energy efficiency. Non Intrusive Load Monitoring (NILM) is one method of load monitoring used for disaggregation purposes. NILM is a technique for identifying individual appliances based on the analysis of the whole residence data retrieved from the main power meter of the house. Our NILM framework starts with data acquisition, followed by data preprocessing, then event detection, feature extraction, then general appliance modeling and identification at the final stage. The event detection stage is a core component of NILM process since event detection techniques lead to the extraction of appliance features. Appliance features are required for the accurate identification of the household devices. In this research work, we aim at developing a new event detection methodology with accurate load disaggregation to extract appliance features. Time-domain features extracted are used for tuning general appliance models for appliance identification and classification steps. We use unsupervised algorithms such as Dynamic Time Warping (DTW). The proposed method relies on detecting areas of operation of each residential appliance based on the power demand. Then, detecting the time at which each selected appliance changes its states. In order to fit with practical existing smart meters capabilities, we work on low sampling data with a frequency of (1/60) Hz. The data is simulated on Load Profile Generator software (LPG), which was not previously taken into consideration for NILM purposes in the literature. LPG is a numerical software that uses behaviour simulation of people inside the house to generate residential energy consumption data. The proposed event detection method targets low consumption loads that are difficult to detect. Also, it facilitates the extraction of specific features used for general appliance modeling. In addition to this, the identification process includes unsupervised techniques such as DTW. To our best knowledge, there exist few unsupervised techniques employed with low sampling data in comparison to the many supervised techniques used for such cases. We extract a power interval at which falls the operation of the selected appliance along with a time vector for the values delimiting the state transitions of the appliance. After this, appliance signatures are formed from extracted power, geometrical and statistical features. Afterwards, those formed signatures are used to tune general model types for appliances identification using unsupervised algorithms. This method is evaluated using both simulated data on LPG and real-time Reference Energy Disaggregation Dataset (REDD). For that, we compute performance metrics using confusion matrix based metrics, considering accuracy, precision, recall and error-rate. The performance analysis of our methodology is then compared with other detection techniques previously used in the literature review, such as detection techniques based on statistical variations and abrupt changes (Variance Sliding Window and Cumulative Sum).

Keywords: electrical disaggregation, DTW, general appliance modeling, event detection

Procedia PDF Downloads 73

Authors: Niklas Ravn-Boess, Nainita Bhowmick, Takamitsu Hattori, Shohei Koide, Christopher Park, Dimitris Placantonakis

Abstract:

Background: Glioblastoma (GBM) is the most common and deadly primary brain malignancy in adults. Tumor propagation, brain invasion, and resistance to therapy critically depend on GBM stem-like cells (GSCs); however, the mechanisms that regulate GSC self-renewal are incompletely understood. Given the aggressiveness and poor prognosis of GBM, it is imperative to find biomarkers that could also translate into novel drug targets. Along these lines, we have identified a cell surface antigen, CD97 (ADGRE5), an adhesion G protein-coupled receptor (GPCR), that is expressed on GBM cells but is absent from non-neoplastic brain tissue. CD97 has been shown to promote invasiveness, angiogenesis, and migration in several human cancers, but its frequency of expression and functional role in regulating GBM growth and survival, and its potential as a therapeutic target has not been investigated. Design: We assessed CD97 mRNA and protein expression in patient derived GBM samples and cell lines using publicly available RNA-sequencing datasets and flow cytometry, respectively. To assess CD97 function, we generated shRNA lentiviral constructs that target a sequence in the CD97 extracellular domain (ECD). A scrambled shRNA (scr) with no predicted targets in the genome was used as a control. We evaluated CD97 shRNA lentivirally transduced GBM cells for Ki67, Annexin V, and DAPI. We also tested CD97 KD cells for their ability to self-renew using clonogenic tumorsphere formation assays. Further, we utilized synthetic Abs (sAbs) generated against the ECD of CD97 to test for potential antitumor effects using patient-derived GBM cell lines. Results: CD97 mRNA expression was expressed at high levels in all GBM samples available in the TCGA cohort. We found high levels of surface CD97 protein expression in 6/6 patient-derived GBM cell cultures, but not human neural stem cells. Flow cytometry confirmed downregulation of CD97 in CD97 shRNA lentivirally transduced cells. CD97 KD induced a significant reduction in cell growth in 3 independent GBM cell lines representing mesenchymal and proneural subtypes, which was accompanied by reduced (~20%) Ki67 staining and increased (~30%) apoptosis. Incubation of GBM cells with sAbs (20 ug/ ml) against the ECD of CD97 for 3 days induced GSC differentiation, as determined by the expression of GFAP and Tubulin. Using three unique GBM patient derived cultures, we found that CD97 KD attenuated the ability of GBM cells to initiate sphere formation by over 300 fold, consistent with an impairment in GSC self-renewal. Conclusion: Loss of CD97 expression in patient-derived GBM cells markedly decreases proliferation, induces cell death, and reduces tumorsphere formation. sAbs against the ECD of CD97 reduce tumorsphere formation, recapitulating the phenotype of CD97 KD, suggesting that sAbs that inhibit CD97 function exhibit anti-tumor activity. Collectively, these findings indicate that CD97 is necessary for the proliferation and survival of human GBM cells and identify CD97 as a promising therapeutically targetable vulnerability in GBM.

Keywords: adhesion GPCR, CD97, GBM stem cell, glioblastoma

Procedia PDF Downloads 133

Authors: Muhammad Ahnaf Zahin, Yaw Adu-Gyamfi

Abstract:

Bus transit is a crucial component of transportation networks, especially in urban areas. Any intelligent transportation system must have accurate real-time information on bus travel times since it minimizes waiting times for passengers at different stations along a route, improves service reliability, and significantly optimizes travel patterns. Bus agencies must enhance the quality of their information service to serve their passengers better and draw in more travelers since people waiting at bus stops are frequently anxious about when the bus will arrive at their starting point and when it will reach their destination. For solving this issue, different models have been developed for predicting bus travel times recently, but most of them are focused on smaller road networks due to their relatively subpar performance in high-density urban areas on a vast network. This paper develops a deep learning-based architecture using a single-step multi-station forecasting approach to predict average bus travel times for numerous routes, stops, and trips on a large-scale network using heterogeneous bus transit data collected from the GTFS database. Over one week, data was gathered from multiple bus routes in Saint Louis, Missouri. In this study, Gated Recurrent Unit (GRU) neural network was followed to predict the mean vehicle travel times for different hours of the day for multiple stations along multiple routes. Historical time steps and prediction horizon were set up to 5 and 1, respectively, which means that five hours of historical average travel time data were used to predict average travel time for the following hour. The spatial and temporal information and the historical average travel times were captured from the dataset for model input parameters. As adjacency matrices for the spatial input parameters, the station distances and sequence numbers were used, and the time of day (hour) was considered for the temporal inputs. Other inputs, including volatility information such as standard deviation and variance of journey durations, were also included in the model to make it more robust. The model's performance was evaluated based on a metric called mean absolute percentage error (MAPE). The observed prediction errors for various routes, trips, and stations remained consistent throughout the day. The results showed that the developed model could predict travel times more accurately during peak traffic hours, having a MAPE of around 14%, and performed less accurately during the latter part of the day. In the context of a complicated transportation network in high-density urban areas, the model showed its applicability for real-time travel time prediction of public transportation and ensured the high quality of the predictions generated by the model.

Keywords: gated recurrent unit, mean absolute percentage error, single-step forecasting, travel time prediction.

Procedia PDF Downloads 68

Authors: R. Tamborrino, F. Rinaudo

Abstract:

Digital technologies offer possibilities to effectively convert historical archives into instruments of knowledge able to provide a guide for the interpretation of historical phenomena. Digital conversion and management of those documents allow the possibility to add other sources in a unique and coherent model that permits the intersection of different data able to open new interpretations and understandings. Urban history uses, among other sources, the inventories that register human activities in a specific space (e.g. cadastres, censuses, etc.). The geographic localisation of that information inside cartographic supports allows for the comprehension and visualisation of specific relationships between different historical realities registering both the urban space and the peoples living there. These links that merge the different nature of data and documentation through a new organisation of the information can suggest a new interpretation of other related events. In all these kinds of analysis, the use of GIS platforms today represents the most appropriate answer. The design of the related databases is the key to realise the ad-hoc instrument to facilitate the analysis and the intersection of data of different origins. Moreover, GIS has become the digital platform where it is possible to add other kinds of data visualisation. This research deals with the industrial development of Turin at the beginning of the 20th century. A census of factories realized just prior to WWI provides the opportunity to test the potentialities of GIS platforms for the analysis of urban landscape modifications during the first industrial development of the town. The inventory includes data about location, activities, and people. GIS is shaped in a creative way linking different sources and digital systems aiming to create a new type of platform conceived as an interface integrating different kinds of data visualisation. The data processing allows linking this information to an urban space, and also visualising the growth of the city at that time. The sources, related to the urban landscape development in that period, are of a different nature. The emerging necessity to build, enlarge, modify and join different buildings to boost the industrial activities, according to their fast development, is recorded by different official permissions delivered by the municipality and now stored in the Historical Archive of the Municipality of Turin. Those documents, which are reports and drawings, contain numerous data on the buildings themselves, including the block where the plot is located, the district, and the people involved such as the owner, the investor, and the engineer or architect designing the industrial building. All these collected data offer the possibility to firstly re-build the process of change of the urban landscape by using GIS and 3D modelling technologies thanks to the access to the drawings (2D plans, sections and elevations) that show the previous and the planned situation. Furthermore, they access information for different queries of the linked dataset that could be useful for different research and targets such as economics, biographical, architectural, or demographical. By superimposing a layer of the present city, the past meets to the present-industrial heritage, and people meet urban history.

Keywords: digital urban history, census, digitalisation, GIS, modelling, digital humanities

Procedia PDF Downloads 190

Authors: Lee Tasker, Ali Karrech, Jeffrey Shragge, Matthew Josh

Abstract:

Monitoring for the deterioration of concrete infrastructure is an important assessment tool for an engineer and difficulties can be experienced with monitoring for deterioration within an infrastructure. If a failure crack, or fluid seepage through such a crack, is observed from the surface often the source location of the deterioration is not known. Geophysical methods are used to assist engineers with assessing the subsurface conditions of materials. Techniques such as Ground Penetrating Radar (GPR) provide information on the location of buried infrastructure such as pipes and conduits, positions of reinforcements within concrete blocks, and regions of voids/cavities behind tunnel lining. This experiment underlines the application of GPR as an infrastructure-monitoring tool to highlight and monitor regions of possible deterioration within a concrete test wall due to an increase in the generation of fractures; in particular, during a time period of applied load to a concrete wall up to and including structural failure. A three-point load was applied to a concrete test wall of dimensions 1700 x 600 x 300 mm³ in increments of 10 kN, until the wall structurally failed at 107.6 kN. At each increment of applied load, the load was kept constant and the wall was scanned using GPR along profile lines across the wall surface. The measured radar amplitude responses of the GPR profiles, at each applied load interval, were reconstructed into depth-slice grids and presented at fixed depth-slice intervals. The corresponding depth-slices were subtracted from each data set to compare the radar amplitude response between datasets and monitor for changes in the radar amplitude response. At lower values of applied load (i.e., 0-60 kN), few changes were observed in the difference of radar amplitude responses between data sets. At higher values of applied load (i.e., 100 kN), closer to structural failure, larger differences in radar amplitude response between data sets were highlighted in the GPR data; up to 300% increase in radar amplitude response at some locations between the 0 kN and 100 kN radar datasets. Distinct regions were observed in the 100 kN difference dataset (i.e., 100 kN-0 kN) close to the location of the final failure crack. The key regions observed were a conical feature located between approximately 3.0-12.0 cm depth from surface and a vertical linear feature located approximately 12.1-21.0 cm depth from surface. These key regions have been interpreted as locations exhibiting an increased change in pore-space due to increased mechanical loading, or locations displaying an increase in volume of micro-cracks, or locations showing the development of a larger macro-crack. The experiment showed that GPR is a useful geophysical monitoring tool to assist engineers with highlighting and monitoring regions of large changes of radar amplitude response that may be associated with locations of significant internal structural change (e.g. crack development). GPR is a non-destructive technique that is fast to deploy in a production setting. GPR can assist with reducing risk and costs in future infrastructure maintenance programs by highlighting and monitoring locations within the structure exhibiting large changes in radar amplitude over calendar-time.

Keywords: 4D GPR, engineering geophysics, ground penetrating radar, infrastructure monitoring

Procedia PDF Downloads 175

Authors: Iman Farasat, Howard M. Salis

Abstract:

Engineered genetic circuits reprogram cellular behavior to act as living computers with applications in detecting cancer, creating self-controlling artificial tissues, and dynamically regulating metabolic pathways. Phenemenological models are often used to simulate and design genetic circuit behavior towards a desired behavior. While such models assume that each circuit component’s function is modular and independent, even small changes in a circuit (e.g. a new promoter, a change in transcription factor expression level, or even a new media) can have significant effects on the circuit’s function. Here, we use statistical thermodynamics to account for the several factors that control transcriptional regulation in bacteria, and experimentally demonstrate the model’s accuracy across 825 measurements in several genetic contexts and hosts. We then employ our first principles model to design, experimentally construct, and characterize a family of signal amplifying genetic circuits (genetic OpAmps) that expand the dynamic range of cell sensors. To develop these models, we needed a new approach to measuring the in vivo binding free energies of transcription factors (TFs), a key ingredient of statistical thermodynamic models of gene regulation. We developed a new high-throughput assay to measure RNA polymerase and TF binding free energies, requiring the construction and characterization of only a few constructs and data analysis (Figure 1A). We experimentally verified the assay on 6 TetR-homolog repressors and a CRISPR/dCas9 guide RNA. We found that our binding free energy measurements quantitatively explains why changing TF expression levels alters circuit function. Altogether, by combining these measurements with our biophysical model of translation (the RBS Calculator) as well as other measurements (Figure 1B), our model can account for changes in TF binding sites, TF expression levels, circuit copy number, host genome size, and host growth rate (Figure 1C). Model predictions correctly accounted for how these 8 factors control a promoter’s transcription rate (Figure 1D). Using the model, we developed a design framework for engineering multi-promoter genetic circuits that greatly reduces the number of degrees of freedom (8 factors per promoter) to a single dimensionless unit. We propose the Ptashne (Pt) number to encapsulate the 8 co-dependent factors that control transcriptional regulation into a single number. Therefore, a single number controls a promoter’s output rather than these 8 co-dependent factors, and designing a genetic circuit with N promoters requires specification of only N Pt numbers. We demonstrate how to design genetic circuits in Pt number space by constructing and characterizing 15 2-repressor OpAmp circuits that act as signal amplifiers when within an optimal Pt region. We experimentally show that OpAmp circuits using different TFs and TF expression levels will only amplify the dynamic range of input signals when their corresponding Pt numbers are within the optimal region. Thus, the use of the Pt number greatly simplifies the genetic circuit design, particularly important as circuits employ more TFs to perform increasingly complex functions.

Keywords: transcription factor, synthetic biology, genetic circuit, biophysical model, binding energy measurement

Procedia PDF Downloads 469

Authors: Darren A. Whitaker, Dan Palmer, Jens Wesholowski, James Flaherty, John Mack, Ahmad B. Albadarin, Gavin Walker

Abstract:

Traditional mechanosynthesis has been performed by either ball milling or manual grinding. However, neither of these techniques allow the easy application of process control. The temperature may change unpredictably due to friction in the process. Hence the amount of energy transferred to the reactants is intrinsically non-uniform. Recently, it has been shown that the use of Twin-Screw extrusion (TSE) can overcome these limitations. Additionally, TSE enables a platform for continuous synthesis or manufacturing as it is an open-ended process, with feedstocks at one end and product at the other. Several materials including metal-organic frameworks (MOFs), co-crystals and small organic molecules have been produced mechanochemically using TSE. The described advantages of TSE are offset by drawbacks such as increased process complexity (a large number of process parameters) and variation in feedstock flow impacting on product quality. To handle the above-mentioned drawbacks, this study utilizes UV-Vis spectrophotometry (InSpectroX, ColVisTec) as an online tool to gain real-time information about the quality of the product. Additionally, this is combined with real-time process information in an Advanced Process Control system (PharmaMV, Perceptive Engineering) allowing full supervision and control of the TSE process. Further, by characterizing the dynamic behavior of the TSE, a model predictive controller (MPC) can be employed to ensure the process remains under control when perturbed by external disturbances. Two reactions were studied; a Knoevenagel condensation reaction of barbituric acid and vanillin and, the direct amidation of hydroquinone by ammonium acetate to form N-Acetyl-para-aminophenol (APAP) commonly known as paracetamol. Both reactions could be carried out continuously using TSE, nuclear magnetic resonance (NMR) spectroscopy was used to confirm the percentage conversion of starting materials to product. This information was used to construct partial least squares (PLS) calibration models within the PharmaMV development system, which relates the percent conversion to product to the acquired UV-Vis spectrum. Once this was complete, the model was deployed within the PharmaMV Real-Time System to carry out automated optimization experiments to maximize the percentage conversion based on a set of process parameters in a design of experiments (DoE) style methodology. With the optimum set of process parameters established, a series of PRBS process response tests (i.e. Pseudo-Random Binary Sequences) around the optimum were conducted. The resultant dataset was used to build a statistical model and associated MPC. The controller maximizes product quality whilst ensuring the process remains at the optimum even as disturbances such as raw material variability are introduced into the system. To summarize, a combination of online spectral monitoring and advanced process control was used to develop a robust system for optimization and control of two TSE based mechanosynthetic processes.

Keywords: continuous synthesis, pharmaceutical, spectroscopy, advanced process control

Procedia PDF Downloads 172

Authors: Jianli Jiang, Bai-Chen Xie

Abstract:

The climate issue has aroused global concern. Achieving sustainable development is a good path for countries to mitigate environmental and climatic pressures, although there are many difficulties. The first step towards sustainable development is to evaluate the environmental efficiency of the energy industry with proper methods. The power sector is a major source of CO2, SO2, and NOx emissions. Evaluating the environmental efficiency (EE) of power systems is the premise to alleviate the terrible situation of energy and the environment. Data Envelopment Analysis (DEA) has been widely used in efficiency studies. However, measuring the efficiency of a system (be it a nation, region, sector, or business) is a challenging task. The classic DEA takes the decision-making units (DMUs) as independent, which neglects the interaction between DMUs. While ignoring these inter-regional links may result in a systematic bias in the efficiency analysis; for instance, the renewable power generated in a certain region may benefit the adjacent regions while the SO2 and CO2 emissions act oppositely. This study proposes a spatial network DEA (SNDEA) with a slack measure that can capture the spatial spillover effects of inputs/outputs among DMUs to measure efficiency. This approach is used to study the EE of China's power system, which consists of generation, transmission, and distribution departments, using a panel dataset from 2014 to 2020. In the empirical example, the energy and patent inputs, the undesirable CO2 output, and the renewable energy (RE) power variables are tested for a significant spatial spillover effect. Compared with the classic network DEA, the SNDEA result shows an obvious difference tested by the global Moran' I index. From a dynamic perspective, the EE of the power system experiences a visible surge from 2015, then a sharp downtrend from 2019, which keeps the same trend with the power transmission department. This phenomenon benefits from the market-oriented reform in the Chinese power grid enacted in 2015. The rapid decline in the environmental efficiency of the transmission department in 2020 was mainly due to the Covid-19 epidemic, which hinders economic development seriously. While the EE of the power generation department witnesses a declining trend overall, this is reasonable, taking the RE power into consideration. The installed capacity of RE power in 2020 is 4.40 times that in 2014, while the power generation is 3.97 times; in other words, the power generation per installed capacity shrank. In addition, the consumption cost of renewable power increases rapidly with the increase of RE power generation. These two aspects make the EE of the power generation department show a declining trend. Incorporation of the interactions among inputs/outputs into the DEA model, this paper proposes an efficiency evaluation method on the basis of the DEA framework, which sheds some light on efficiency evaluation in regional studies. Furthermore, the SNDEA model and the spatial DEA concept can be extended to other fields, such as industry, country, and so on.

Keywords: spatial network DEA, environmental efficiency, sustainable development, power system

Procedia PDF Downloads 101

Authors: Noura Al Akkari, Aurélie Foucquier, Sylvain Lespinats

Abstract:

Load monitoring is a management process for energy consumption towards energy savings and energy efficiency. Non Intrusive Load Monitoring (NILM) is one method of load monitoring used for disaggregation purposes. NILM is a technique for identifying individual appliances based on the analysis of the whole residence data retrieved from the main power meter of the house. Our NILM framework starts with data acquisition, followed by data preprocessing, then event detection, feature extraction, then general appliance modeling and identification at the final stage. The event detection stage is a core component of NILM process since event detection techniques lead to the extraction of appliance features. Appliance features are required for the accurate identification of the household devices. In this research work, we aim at developing a new event detection methodology with accurate load disaggregation to extract appliance features. Time-domain features extracted are used for tuning general appliance models for appliance identification and classification steps. We use unsupervised algorithms such as Dynamic Time Warping (DTW). The proposed method relies on detecting areas of operation of each residential appliance based on the power demand. Then, detecting the time at which each selected appliance changes its states. In order to fit with practical existing smart meters capabilities, we work on low sampling data with a frequency of (1/60) Hz. The data is simulated on Load Profile Generator software (LPG), which was not previously taken into consideration for NILM purposes in the literature. LPG is a numerical software that uses behaviour simulation of people inside the house to generate residential energy consumption data. The proposed event detection method targets low consumption loads that are difficult to detect. Also, it facilitates the extraction of specific features used for general appliance modeling. In addition to this, the identification process includes unsupervised techniques such as DTW. To our best knowledge, there exist few unsupervised techniques employed with low sampling data in comparison to the many supervised techniques used for such cases. We extract a power interval at which falls the operation of the selected appliance along with a time vector for the values delimiting the state transitions of the appliance. After this, appliance signatures are formed from extracted power, geometrical and statistical features. Afterwards, those formed signatures are used to tune general model types for appliances identification using unsupervised algorithms. This method is evaluated using both simulated data on LPG and real-time Reference Energy Disaggregation Dataset (REDD). For that, we compute performance metrics using confusion matrix based metrics, considering accuracy, precision, recall and error-rate. The performance analysis of our methodology is then compared with other detection techniques previously used in the literature review, such as detection techniques based on statistical variations and abrupt changes (Variance Sliding Window and Cumulative Sum).

Keywords: general appliance model, non intrusive load monitoring, events detection, unsupervised techniques;

Procedia PDF Downloads 77

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

Abstract:

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)

Procedia PDF Downloads 427

Authors: Fernanda Bravo Cornejo, Camilo Cerda Sarabia, Belén Díaz Díaz, Diego Santibañez Oyarce, Esteban Gómez Terán, Hugo Osses Prado, Raúl Caulier-Cisterna, Jorge Vergara-Quezada, Ana Moya-Beltrán

Abstract:

Streptococcus pyogenes is a gram-positive bacteria involved in a wide range of diseases and is a major-human-specific bacterial pathogen. In Chile, this year the 'Ministerio de Salud' declared an alert due to the increase in strains throughout the year. This increase can be attributed to the multitude of factors including antimicrobial resistance (AMR) and Virulence Factors (VF). Understanding these VF and AMR is crucial for developing effective strategies and improving public health responses. Moreover, experimental identification and characterization of these pathogenic mechanisms are labor-intensive and time-consuming. Therefore, new computational methods are required to provide robust techniques for accelerating this identification. Advances in Machine Learning (ML) algorithms represent the opportunity to refine and accelerate the discovery of VF associated with Streptococcus pyogenes. In this work, we evaluate the accuracy of various machine learning models in predicting the virulence factors and antimicrobial resistance of Streptococcus pyogenes, with the objective of providing new methods for identifying the pathogenic mechanisms of this organism.Our comprehensive approach involved the download of 32,798 genbank files of S. pyogenes from NCBI dataset, coupled with the incorporation of data from Virulence Factor Database (VFDB) and Antibiotic Resistance Database (CARD) which contains sequences of AMR gene sequence and resistance profiles. These datasets provided labeled examples of both virulent and non-virulent genes, enabling a robust foundation for feature extraction and model training. We employed preprocessing, characterization and feature extraction techniques on primary nucleotide/amino acid sequences and selected the optimal more for model training. The feature set was constructed using sequence-based descriptors (e.g., k-mers and One-hot encoding), and functional annotations based on database prediction. The ML models compared are logistic regression, decision trees, support vector machines, neural networks among others. The results of this work show some differences in accuracy between the algorithms, these differences allow us to identify different aspects that represent unique opportunities for a more precise and efficient characterization and identification of VF and AMR. This comparative analysis underscores the value of integrating machine learning techniques in predicting S. pyogenes virulence and AMR, offering potential pathways for more effective diagnostic and therapeutic strategies. Future work will focus on incorporating additional omics data, such as transcriptomics, and exploring advanced deep learning models to further enhance predictive capabilities.

Keywords: antibiotic resistance, streptococcus pyogenes, virulence factors., machine learning

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Authors: Jia Li, Xing Wei, Yuchen Hong, Yang Lu

Abstract:

Detecting vehicle behavior has always been the focus of intelligent transportation, but with the explosive growth of the number of vehicles and the complexity of the road environment, the vehicle behavior videos captured by traditional surveillance have been unable to satisfy the study of vehicle behavior. The traditional method of manually labeling vehicle behavior is too time-consuming and labor-intensive, but the existing object detection and tracking algorithms have poor practicability and low behavioral location detection rate. This paper proposes a vehicle behavior detection algorithm based on the dual-stream convolution network and the multi-dimensional video dynamic detection network. In the videos, the straight-line behavior of the vehicle will default to the background behavior. The Changing lanes, turning and turning around are set as target behaviors. The purpose of this model is to automatically mark the target behavior of the vehicle from the untrimmed videos. First, the target behavior proposals in the long video are extracted through the dual-stream convolution network. The model uses a dual-stream convolutional network to generate a one-dimensional action score waveform, and then extract segments with scores above a given threshold M into preliminary vehicle behavior proposals. Second, the preliminary proposals are pruned and identified using the multi-dimensional video dynamic detection network. Referring to the hierarchical reinforcement learning, the multi-dimensional network includes a Timer module and a Spacer module, where the Timer module mines time information in the video stream and the Spacer module extracts spatial information in the video frame. The Timer and Spacer module are implemented by Long Short-Term Memory (LSTM) and start from an all-zero hidden state. The Timer module uses the Transformer mechanism to extract timing information from the video stream and extract features by linear mapping and other methods. Finally, the model fuses time information and spatial information and obtains the location and category of the behavior through the softmax layer. This paper uses recall and precision to measure the performance of the model. Extensive experiments show that based on the dataset of this paper, the proposed model has obvious advantages compared with the existing state-of-the-art behavior detection algorithms. When the Time Intersection over Union (TIoU) threshold is 0.5, the Average-Precision (MP) reaches 36.3% (the MP of baselines is 21.5%). In summary, this paper proposes a vehicle behavior detection model based on multi-dimensional dynamic detection network. This paper introduces spatial information and temporal information to extract vehicle behaviors in long videos. Experiments show that the proposed algorithm is advanced and accurate in-vehicle timing behavior detection. In the future, the focus will be on simultaneously detecting the timing behavior of multiple vehicles in complex traffic scenes (such as a busy street) while ensuring accuracy.

Keywords: vehicle behavior detection, convolutional neural network, long short-term memory, deep learning

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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: George Zhou, Yunchan Chen, Candace Chien

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Kidney replacement therapy is the current standard of care for end-stage renal diseases. In-center or home hemodialysis remains an integral component of the therapeutic regimen. Arteriovenous fistulas (AVF) make up the vascular circuit through which blood is filtered and returned. Naturally, AVF patency determines whether adequate clearance and filtration can be achieved and directly influences clinical outcomes. Our aim was to build a deep learning model for automated AVF stenosis screening based on the sound of blood flow through the AVF. A total of 311 patients with AVF were enrolled in this study. Blood flow sounds were collected using a digital stethoscope. For each patient, blood flow sounds were collected at 6 different locations along the patient’s AVF. The 6 locations are artery, anastomosis, distal vein, middle vein, proximal vein, and venous arch. A total of 1866 sounds were collected. The blood flow sounds are labeled as “patent” (normal) or “stenotic” (abnormal). The labels are validated from concurrent ultrasound. Our dataset included 1527 “patent” and 339 “stenotic” sounds. We show that blood flow sounds vary significantly along the AVF. For example, the blood flow sound is loudest at the anastomosis site and softest at the cephalic arch. Contextualizing the sound with location metadata significantly improves classification performance. How to encode and incorporate categorical metadata is an active area of research1. Herein, we study ordinal (i.e., integer) encoding schemes. The numerical representation is concatenated to the flattened feature vector. We train a vision transformer (ViT) on spectrogram image representations of the sound and demonstrate that using scalar multiples of our integer encodings improves classification performance. Models are evaluated using a 10-fold cross-validation procedure. The baseline performance of our ViT without any location metadata achieves an AuROC and AuPRC of 0.68 ± 0.05 and 0.28 ± 0.09, respectively. Using the following encodings of Artery:0; Arch: 1; Proximal: 2; Middle: 3; Distal 4: Anastomosis: 5, the ViT achieves an AuROC and AuPRC of 0.69 ± 0.06 and 0.30 ± 0.10, respectively. Using the following encodings of Artery:0; Arch: 10; Proximal: 20; Middle: 30; Distal 40: Anastomosis: 50, the ViT achieves an AuROC and AuPRC of 0.74 ± 0.06 and 0.38 ± 0.10, respectively. Using the following encodings of Artery:0; Arch: 100; Proximal: 200; Middle: 300; Distal 400: Anastomosis: 500, the ViT achieves an AuROC and AuPRC of 0.78 ± 0.06 and 0.43 ± 0.11. respectively. Interestingly, we see that using increasing scalar multiples of our integer encoding scheme (i.e., encoding “venous arch” as 1,10,100) results in progressively improved performance. In theory, the integer values do not matter since we are optimizing the same loss function; the model can learn to increase or decrease the weights associated with location encodings and converge on the same solution. However, in the setting of limited data and computation resources, increasing the importance at initialization either leads to faster convergence or helps the model escape a local minimum.

Keywords: arteriovenous fistula, blood flow sounds, metadata encoding, deep learning

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Authors: Sachin Jain, Daniel Perez-Astudillo, Dunia A. Bachour, Antonio P. Sanfilippo

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The future of solar energy in Qatar is evolving steadily. Hence, high-quality spatial solar radiation data is of the uttermost requirement for any planning and commissioning of solar technology. Generally, two types of solar radiation data are available: satellite data and ground observations. Satellite solar radiation data is developed by the physical and statistical model. Ground data is collected by solar radiation measurement stations. The ground data is of high quality. However, they are limited to distributed point locations with the high cost of installation and maintenance for the ground stations. On the other hand, satellite solar radiation data is continuous and available throughout geographical locations, but they are relatively less accurate than ground data. To utilize the advantage of both data, a product has been developed here which provides spatial continuity and higher accuracy than any of the data alone. The popular satellite databases: National Solar radiation Data Base, NSRDB (PSM V3 model, spatial resolution: 4 km) is chosen here for merging with ground-measured solar radiation measurement in Qatar. The spatial distribution of ground solar radiation measurement stations is comprehensive in Qatar, with a network of 13 ground stations. The monthly average of the daily total Global Horizontal Irradiation (GHI) component from ground and satellite data is used for error analysis. The normalized root means square error (NRMSE) values of 3.31%, 6.53%, and 6.63% for October, November, and December 2019 were observed respectively when comparing in-situ and NSRDB data. The method is based on the Empirical Bayesian Kriging Regression Prediction model available in ArcGIS, ESRI. The workflow of the algorithm is based on the combination of regression and kriging methods. A regression model (OLS, ordinary least square) is fitted between the ground and NSBRD data points. A semi-variogram is fitted into the experimental semi-variogram obtained from the residuals. The kriging residuals obtained after fitting the semi-variogram model were added to NSRBD data predicted values obtained from the regression model to obtain the final predicted values. The NRMSE values obtained after merging are respectively 1.84%, 1.28%, and 1.81% for October, November, and December 2019. One more explanatory variable, that is the ground elevation, has been incorporated in the regression and kriging methods to reduce the error and to provide higher spatial resolution (30 m). The final GHI maps have been created after merging, and NRMSE values of 1.24%, 1.28%, and 1.28% have been observed for October, November, and December 2019, respectively. The proposed merging method has proven as a highly accurate method. An additional method is also proposed here to generate calibrated maps by using regression and kriging model and further to use the calibrated model to generate solar radiation maps from the explanatory variable only when not enough historical ground data is available for long-term analysis. The NRMSE values obtained after the comparison of the calibrated maps with ground data are 5.60% and 5.31% for November and December 2019 month respectively.

Keywords: global horizontal irradiation, GIS, empirical bayesian kriging regression prediction, NSRDB

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Authors: Serap Durkut, A. Eser Elcin, Y. Murat Elcin

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Stimuli-sensitive polymeric hydrogels have received extensive attention in the biomedical field due to their sensitivity to physical and chemical stimuli (temperature, pH, ionic strength, light, etc.). This study describes the rheological properties of a novel thermoresponsive poly(N-vinylcaprolactam)-g-collagen hydrogel. In the study, we first synthesized a facile and novel synthetic carboxyl group-terminated thermo-responsive poly(N-vinylcaprolactam)-COOH (PNVCL-COOH) via free radical polymerization. Further, this compound was effectively grafted with native collagen, by utilizing the covalent bond between the carboxylic acid groups at the end of the chains and amine groups of the collagen using cross-linking agent (EDC/NHS), forming PNVCL-g-Col. Newly-formed hybrid hydrogel displayed novel properties, such as increased mechanical strength and thermoresponsive characteristics. PNVCL-g-Col showed low critical solution temperature (LCST) at 38ºC, which is very close to the body temperature. Rheological studies determine structural–mechanical properties of the materials and serve as a valuable tool for characterizing. The rheological properties of hydrogels are described in terms of two dynamic mechanical properties: the elastic modulus G′ (also known as dynamic rigidity) representing the reversible stored energy of the system, and the viscous modulus G″, representing the irreversible energy loss. In order to characterize the PNVCL-g-Col, the rheological properties were measured in terms of the function of temperature and time during phase transition. Below the LCST, favorable interactions allowed the dissolution of the polymer in water via hydrogen bonding. At temperatures above the LCST, PNVCL molecules within PNVCL-g-Col aggregated due to dehydration, causing the hydrogel structure to become dense. When the temperature reached ~36ºC, both the G′ and G″ values crossed over. This indicates that PNVCL-g-Col underwent a sol-gel transition, forming an elastic network. Following temperature plateau at 38ºC, near human body temperature the sample displayed stable elastic network characteristics. The G′ and G″ values of the PNVCL-g-Col solutions sharply increased at 6-9 minute interval, due to rapid transformation into gel-like state and formation of elastic networks. Copolymerization with collagen leads to an increase in G′, as collagen structure contains a flexible polymer chain, which bestows its elastic properties. Elasticity of the proposed structure correlates with the number of intermolecular cross-links in the hydrogel network, increasing viscosity. However, at 8 minutes, G′ and G″ values sharply decreased for pure collagen solutions due to the decomposition of the elastic and viscose network. Complex viscosity is related to the mechanical performance and resistance opposing deformation of the hydrogel. Complex viscosity of PNVCL-g-Col hydrogel was drastically changed with temperature and the mechanical performance of PNVCL-g-Col hydrogel network increased, exhibiting lesser deformation. Rheological assessment of the novel thermo-responsive PNVCL-g-Col hydrogel, exhibited that the network has stronger mechanical properties due to both permanent stable covalent bonds and physical interactions, such as hydrogen- and hydrophobic bonds depending on temperature.

Keywords: poly(N-vinylcaprolactam)-g-collagen, thermoresponsive polymer, rheology, elastic modulus, stimuli-sensitive

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Authors: Ram Sharma, Esha Chatterjee, Santosh Kumar Guru, Kunal Nepali

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A tractable anti-lung cancer agent was identified via the installation of a Ring C expanded synthetic analogue of the alkaloid vasicinone [7,8,9,10-tetrahydroazepino[2,1-b] quinazolin-12(6H)-one (TAZQ)] as a surface recognition part in the HDAC inhibitory three-component model. Noteworthy to mention that the candidature of TAZQ was deemed suitable for accommodation in HDAC inhibitory pharmacophore as per the results of the fragment recruitment process conducted by our laboratory. TAZQ was pinpointed through the fragment screening program as a synthetically flexible fragment endowed with some moderate cell growth inhibitory activity against the lung cancer cell lines, and it was anticipated that the use of the aforementioned fragment to generate hydroxamic acid functionality (zinc-binding motif) bearing HDAC inhibitors would boost the antitumor efficacy of TAZQ. Consistent with our aim of applying epigenetic targets to the treatment of lung cancer, a strikingly potent anti-lung cancer scaffold (compound 6) was pinpointed through a series of in-vitro experiments. Notably, the compounds manifested a magnificent activity profile against KRAS and EGFR mutant lung cancer cell lines (IC50 = 0.80 - 0.96 µM), and the effects were found to be mediated through preferential HDAC6 inhibition (IC50 = 12.9 nM). In addition to HDAC6 inhibition, the compounds also elicited HDAC1 and HDAC3 inhibitory activity with an IC50 value of 49.9 nM and 68.5 nM, respectively. The HDAC inhibitory ability of compound 6 was also confirmed from the results of the western blot experiment that revealed its potential to decrease the expression levels of HDAC isoforms (HDAC1, HDAC3, and HDAC6). Noteworthy to mention that complete downregulation of the HDAC6 isoform was exerted by compound 6 at 0.5 and 1 µM. Moreover, in another western blot experiment, treatment with hydroxamic acid 6 led to upregulation of H3 acK9 and α-Tubulin acK40 levels, ascertaining its inhibitory activity toward both the class I HDACs and Class II B HDACs. The results of other assays were also encouraging as treatment with compound 6 led to the suppression of the colony formation ability of A549 cells, induction of apoptosis, and increase in autophagic flux. In silico studies led us to rationalize the results of the experimental assay, and some key interactions of compound 6 with the amino acid residues of HDAC isoforms were identified. In light of the impressive activity spectrum of compound 6, a pH-responsive nanocarrier (hyaluronic acid-compound 6 nanoparticles) was prepared. The dialysis bag approach was used for the assessment of the nanoparticles under both normal and acidic circumstances, and the pH-sensitive nature of hyaluronic acid-compound 6 nanoparticles was confirmed. Delightfully, the nanoformulation was devoid of cytotoxicity against the L929 mouse fibroblast cells (normal settings) and exhibited selective cytotoxicity towards the A549 lung cancer cell lines. In a nutshell, compound 6 appears to be a promising adduct, and a detailed investigation of this compound might yield a therapeutic for the treatment of lung cancer.

Keywords: HDAC inhibitors, lung cancer, scaffold, hyaluronic acid, nanoparticles

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