Search results for: gene expression profiles
Commenced in January 2007
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Edition: International
Paper Count: 3877

Search results for: gene expression profiles

277 Characterization and Evaluation of the Dissolution Increase of Molecular Solid Dispersions of Efavirenz

Authors: Leslie Raphael de M. Ferraz, Salvana Priscylla M. Costa, Tarcyla de A. Gomes, Giovanna Christinne R. M. Schver, Cristóvão R. da Silva, Magaly Andreza M. de Lyra, Danilo Augusto F. Fontes, Larissa A. Rolim, Amanda Carla Q. M. Vieira, Miracy M. de Albuquerque, Pedro J. Rolim-Neto

Abstract:

Efavirenz (EFV) is a drug used as first-line treatment of AIDS. However, it has poor aqueous solubility and wettability, presenting problems in the gastrointestinal tract absorption and bioavailability. One of the most promising strategies to improve the solubility is the use of solid dispersions (SD). Therefore, this study aimed to characterize SD EFZ with the polymers: PVP-K30, PVPVA 64 and SOLUPLUS in order to find an optimal formulation to compose a future pharmaceutical product for AIDS therapy. Initially, Physical Mixtures (PM) and SD with the polymers were obtained containing 10, 20, 50 and 80% of drug (w/w) by the solvent method. The best formulation obtained between the SD was selected by in vitro dissolution test. Finally, the drug-carrier system chosen, in all ratios obtained, were analyzed by the following techniques: Differential Scanning Calorimetry (DSC), polarization microscopy, Scanning Electron Microscopy (SEM) and spectrophotometry of absorption in the region of infrared (IR). From the dissolution profiles of EFV, PM and SD, the values of area Under The Curve (AUC) were calculated. The data showed that the AUC of all PM is greater than the isolated EFV, this result is derived from the hydrophilic properties of the polymers thus favoring a decrease in surface tension between the drug and the dissolution medium. In adittion, this ensures an increasing of wettability of the drug. In parallel, it was found that SD whom had higher AUC values, were those who have the greatest amount of polymer (with only 10% drug). As the amount of drug increases, it was noticed that these results either decrease or are statistically similar. The AUC values of the SD using the three different polymers, followed this decreasing order: SD PVPVA 64-EFV 10% > SD PVP-K30-EFV 10% > SD Soluplus®-EFV 10%. The DSC curves of SD’s did not show the characteristic endothermic event of drug melt process, suggesting that the EFV was converted to its amorphous state. The analysis of polarized light microscopy showed significant birefringence of the PM’s, but this was not observed in films of SD’s, thus suggesting the conversion of the drug from the crystalline to the amorphous state. In electron micrographs of all PM, independently of the percentage of the drug, the crystal structure of EFV was clearly detectable. Moreover, electron micrographs of the SD with the two polymers in different ratios investigated, we observed the presence of particles with irregular size and morphology, also occurring an extensive change in the appearance of the polymer, not being possible to differentiate the two components. IR spectra of PM corresponds to the overlapping of polymer and EFV bands indicating thereby that there is no interaction between them, unlike the spectra of all SD that showed complete disappearance of the band related to the axial deformation of the NH group of EFV. Therefore, this study was able to obtain a suitable formulation to overcome the solubility limitations of the EFV, since SD PVPVA 64-EFZ 10% was chosen as the best system in delay crystallization of the prototype, reaching higher levels of super saturation.

Keywords: characterization, dissolution, Efavirenz, solid dispersions

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276 Using Differentiated Instruction Applying Cognitive Approaches and Strategies for Teaching Diverse Learners

Authors: Jolanta Jonak, Sylvia Tolczyk

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Educational systems are tasked with preparing students for future success in academic or work environments. Schools strive to achieve this goal, but often it is challenging as conventional teaching approaches are often ineffective in increasingly diverse educational systems. In today’s ever-increasing global society, educational systems become increasingly diverse in terms of cultural and linguistic differences, learning preferences and styles, ability and disability. Through increased understanding of disabilities and improved identification processes, students having some form of disabilities tend to be identified earlier than in the past, meaning that more students with identified disabilities are being supported in our classrooms. Also, a large majority of students with disabilities are educated in general education environments. Due to cognitive makeup and life experiences, students have varying learning styles and preferences impacting how they receive and express what they are learning. Many students come from bi or multilingual households and with varying proficiencies in the English language, further impacting their learning. All these factors need to be seriously considered when developing learning opportunities for student's. Educators try to adjust their teaching practices as they discover that conventional methods are often ineffective in reaching each student’s potential. Many teachers do not have the necessary educational background or training to know how to teach students whose learning needs are more unique and may vary from the norm. This is further complicated by the fact that many classrooms lack consistent access to interventionists/coaches that are adequately trained in evidence-based approaches to meet the needs of all students, regardless of what their academic needs may be. One evidence-based way for providing successful education for all students is by incorporating cognitive approaches and strategies that tap into affective, recognition, and strategic networks in the student's brain. This can be done through Differentiated Instruction (DI). Differentiated Instruction is increasingly recognized model that is established on the basic principles of Universal Design for Learning. This form of support ensures that regardless of the students’ learning preferences and cognitive learning profiles, they have opportunities to learn through approaches that are suitable to their needs. This approach improves the educational outcomes of students with special needs and it benefits other students as it accommodates learning styles as well as the scope of unique learning needs that are evident in the typical classroom setting. Differentiated Instruction also is recognized as an evidence-based best practice in education and is highly effective when it is implemented within the tiered system of the Response to Intervention (RTI) model. Recognition of DI becomes more common; however, there is still limited understanding of the effective implementation and use of strategies that can create unique learning environments for each student within the same setting. Through employing knowledge of a variety of instructional strategies, general and special education teachers can facilitate optimal learning for all students, with and without a disability. A desired byproduct of DI is that it can eliminate inaccurate perceptions about the students’ learning abilities, unnecessary referrals for special education evaluations, and inaccurate decisions about the presence of a disability.

Keywords: differentiated instruction, universal design for learning, special education, diversity

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275 Valuing Cultural Ecosystem Services of Natural Treatment Systems Using Crowdsourced Data

Authors: Andrea Ghermandi

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Natural treatment systems such as constructed wetlands and waste stabilization ponds are increasingly used to treat water and wastewater from a variety of sources, including stormwater and polluted surface water. The provision of ancillary benefits in the form of cultural ecosystem services makes these systems unique among water and wastewater treatment technologies and greatly contributes to determine their potential role in promoting sustainable water management practices. A quantitative analysis of these benefits, however, has been lacking in the literature. Here, a critical assessment of the recreational and educational benefits in natural treatment systems is provided, which combines observed public use from a survey of managers and operators with estimated public use as obtained using geotagged photos from social media as a proxy for visitation rates. Geographic Information Systems (GIS) are used to characterize the spatial boundaries of 273 natural treatment systems worldwide. Such boundaries are used as input for the Application Program Interfaces (APIs) of two popular photo-sharing websites (Flickr and Panoramio) in order to derive the number of photo-user-days, i.e., the number of yearly visits by individual photo users in each site. The adequateness and predictive power of four univariate calibration models using the crowdsourced data as a proxy for visitation are evaluated. A high correlation is found between photo-user-days and observed annual visitors (Pearson's r = 0.811; p-value < 0.001; N = 62). Standardized Major Axis (SMA) regression is found to outperform Ordinary Least Squares regression and count data models in terms of predictive power insofar as standard verification statistics – such as the root mean square error of prediction (RMSEP), the mean absolute error of prediction (MAEP), the reduction of error (RE), and the coefficient of efficiency (CE) – are concerned. The SMA regression model is used to estimate the intensity of public use in all 273 natural treatment systems. System type, influent water quality, and area are found to statistically affect public use, consistently with a priori expectations. Publicly available information regarding the home location of the sampled visitors is derived from their social media profiles and used to infer the distance they are willing to travel to visit the natural treatment systems in the database. Such information is analyzed using the travel cost method to derive monetary estimates of the recreational benefits of the investigated natural treatment systems. Overall, the findings confirm the opportunities arising from an integrated design and management of natural treatment systems, which combines the objectives of water quality enhancement and provision of cultural ecosystem services through public use in a multi-functional approach and compatibly with the need to protect public health.

Keywords: constructed wetlands, cultural ecosystem services, ecological engineering, waste stabilization ponds

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274 Auditory Function in Hypothyroidism as Compared to Controls

Authors: Mrunal Phatak

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Introduction: Thyroid hormone is important for the normal function of the auditory system. Hearing impairment can occur insidiously in subclinical hypothyroidism. The present study was undertaken with the aim of evaluating audiological tests like tuning fork tests, pure tone audiometry, brainstem evoked auditory potentials (BAEPs), and auditory reaction time (ART) in hypothyroid women and in age and sex-matched controls to evaluate the effect of thyroid hormone on hearing. The objective of the study was to investigate hearing status by the audiological profile in hypothyroidism (group 1) and healthy controls (group 2) to compare the audiological profile between these groups and find the correlation of levels of TSH, T3 and T4 with the above parameters. Material and methods: A total sample size of 124 women in the age group of 30 to 50 years was recruited and divided into the Cases group comprising 62 newly diagnosed hypothyroid women and a Control group having 62 women with normal thyroid profiles. Otoscopic examination, tuning fork tests, Pure tone audiometry tests (PTA). Brain Stem Auditory Evoked Potential (BAEP) and Auditory Reaction Time (ART) were done in both ears, i.e., a total of 248 ears of all subjects. Results: By BAEPs, hearing impairment was detected in a total of 64 years (51.61%). A significant increase was seen in Wave V latency, IPL I-V and IPL III-V, and the decrease was seen in the amplitude of Wave I and V in both the ears cases. A positive correlation of Wave V latency of the Right and Left ears is seen with TSH levels (p < 0.001) and a negative correlation with T3 (>0.05) and with T4 (p < 0.01). The negative correlation of wave V amplitude of the Right and Left ears is seen with TSH levels (p < 0.001), and a significant positive correlation is seen with T3 and T4. Pure tone audiometry parameters showed hearing impairment of conductive (31.29%), sensorineural (36.29%), as well as mixed type (15.32%). Hearing loss was mild in 65.32% of ears and moderate in 17.74% of ears. Pure tone averages (PTA) were significantly increased in cases than in controls in both ears. A significant positive correlation of PTA of Right and Left ears is seen with TSH levels (p<0.05). A negative correlation between T3 and T4 is seen. A significant increase in HF ART and LF ART is seen in cases as compared to controls. A positive correlation between ART of high frequency and low frequency is seen with TSH levels and a negative correlation with T3 and T4 (p > 0.05). Conclusion: The abnormal BAEPs in hypothyroid women suggest an impaired central auditory pathway. BAEP abnormalities are indicative of a nonspecific injury in the bulbo-ponto-mesencephalic centers. The results of auditory investigations suggest a causal relationship between hypothyroidism and hearing loss. The site of lesion in the auditory pathway is probably at several levels, namely, in the middle ear and at cochlear and retrocochlear sites. Prolonged ART also suggests an impairment in central processing mechanisms. The results of the present study conclude that the probable reason for hearing impairment in hypothyroidism may be delayed impulse conduction in the acoustic nerve up to the level of the midbrain (IPL I-V, III-V), particularly the inferior colliculus (wave V). There is also impairment in central processing mechanisms, as shown by prolonged ART.

Keywords: hypothyroidism, deafness, pure tone audiometry, brain stem auditory evoked potential

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273 Behavioral Analysis of Anomalies in Intertemporal Choices Through the Concept of Impatience and Customized Strategies for Four Behavioral Investor Profiles With an Application of the Analytic Hierarchy Process: A Case Study

Authors: Roberta Martino, Viviana Ventre

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The Discounted Utility Model is the essential reference for calculating the utility of intertemporal prospects. According to this model, the value assigned to an outcome is the smaller the greater the distance between the moment in which the choice is made and the instant in which the outcome is perceived. This diminution determines the intertemporal preferences of the individual, the psychological significance of which is encapsulated in the discount rate. The classic model provides a discount rate of linear or exponential nature, necessary for temporally consistent preferences. Empirical evidence, however, has proven that individuals apply discount rates with a hyperbolic nature generating the phenomenon of intemporal inconsistency. What this means is that individuals have difficulty managing their money and future. Behavioral finance, which analyzes the investor's attitude through cognitive psychology, has made it possible to understand that beyond individual financial competence, there are factors that condition choices because they alter the decision-making process: behavioral bias. Since such cognitive biases are inevitable, to improve the quality of choices, research has focused on a personalized approach to strategies that combines behavioral finance with personality theory. From the considerations, it emerges the need to find a procedure to construct the personalized strategies that consider the personal characteristics of the client, such as age or gender, and his personality. The work is developed in three parts. The first part discusses and investigates the weight of the degree of impatience and impatience decrease in the anomalies of the discounted utility model. Specifically, the degree of decrease in impatience quantifies the impact that emotional factors generated by haste and financial market agitation have on decision making. The second part considers the relationship between decision making and personality theory. Specifically, four behavioral categories associated with four categories of behavioral investors are considered. This association allows us to interpret intertemporal choice as a combination of bias and temperament. The third part of the paper presents a method for constructing personalized strategies using Analytic Hierarchy Process. Briefly: the first level of the analytic hierarchy process considers the goal of the strategic plan; the second level considers the four temperaments; the third level compares the temperaments with the anomalies of the discounted utility model; and the fourth level contains the different possible alternatives to be selected. The weights of the hierarchy between level 2 and level 3 are constructed considering the degrees of decrease in impatience derived for each temperament with an experimental phase. The results obtained confirm the relationship between temperaments and anomalies through the degree of decrease in impatience and highlight that the actual impact of emotions in decision making. Moreover, it proposes an original and useful way to improve financial advice. Inclusion of additional levels in the Analytic Hierarchy Process can further improve strategic personalization.

Keywords: analytic hierarchy process, behavioral finance anomalies, intertemporal choice, personalized strategies

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272 Anti-Arthritic Effect of a Herbal Diet Formula Comprising Fruits of Rosa Multiflora and Flowers of Lonicera Japonica

Authors: Brian Chi Yan Cheng, Hui Guo, Tao Su, Xiu‐qiong Fu, Ting Li, Zhi‐ling Yu

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Rheumatoid arthritis (RA) affects around 1% of the globe population. Yet, there is still no cure for RA. Toll-like receptor 4 (TLR4) signalling has been found to be involved in the pathogenesis of RA, making it a potential therapeutic target for RA treatment. A herbal formula (RL) consisting of fruits of Rosa Multiflora (Eijitsu rose) and flowers of Lonicera Japonica (Japanese honeysuckle) has been used in treating various inflammatory disorders for more than a thousand year. Both of them are rich sources of nutrients and bioactive phytochemicals, which can be used in producing different food products and supplements. In this study, we would evaluate the anti-arthritic effect of RL on collagen-induced arthritis (CIA) in rats and investigate the involvement of TLR4 signaling in the mode of action of RL. Anti-arthritic efficacy was evaluated using CIA rats induced by bovine type II collagen. The treatment groups were treated with RL (82.5, 165, and 330 mg/kg bw per day, p.o.) or positive control indomethacin (0.25 mg/kg bw per day, p.o.) for 35 days. Clinical signs (hind paw volume and arthritis severity scores), changes in serum inflammatory mediators, pro-/antioxidant status, histological and radiographic changes of joints were investigated. Spleens and peritoneal macrophages were used to determine the effects of RL on innate and adaptive immune responses in CIA rats. The involvement of TLR4 signalling pathways in the anti-arthritic effect of RL was examined in cartilage tissue of CIA rats, murine RAW264.7 macrophages and human THP-1 monocytic cells. The severity of arthritis in the CIA rats was significantly attenuated by RL. Antioxidant status, histological score and radiographic score were efficiently improved by RL. RL could also dose-dependently inhibit pro-inflammatory cytokines in serum of CIA rats. RL significantly inhibited the production of various pro-inflammatory mediators, the expression and/or activity of the components of TLR4 signalling pathways in animal tissue and cell lines. RL possesses anti-arthritic effect on collagen-induced arthritis in rats. The therapeutic effect of RL may be related to its inhibition on pro-inflammatory cytokines in serum. The inhibition of the TAK1/NF-κB and TAK1/MAPK pathways participate in the anti-arthritic effects of RL. This provides a pharmacological justification for the dietary use of RL in the control of various arthritic diseases. Further investigation should be done to develop RL into a anti-arthritic food products and/or supplements.

Keywords: japanese honeysuckle, rheumatoid arthritis, rosa multiflora, rosehip

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271 4D Monitoring of Subsurface Conditions in Concrete Infrastructure Prior to Failure Using Ground Penetrating Radar

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

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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

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270 Assessment of the Effect of Ethanolic Leaf Extract of Annona squamosa L. on Den Induced Hepatocellular Carcinoma in Experimental Animals

Authors: Vanitha Varadharaj, Vijalakshmi Krishnamurthy

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Annona squamosa Linn, commonly known as Sugar apple, belonging to the family Annonaceae, is said to show varied medicinal effects, including insecticide, antiovulatory and abortifacient. The alkaloid and flavonoids present in Annona squamosa leaf has proved to have antioxidant activity. The present work has been planned to investigate the effect of ethanolic leaf extract of Annona squamosa leaf on Den Induced wistar albino rats. The study was carried out to analyze the biochemical Parmeters like Total Proteins, Bilirubin, Enzymatic and Non –Enzymatic enzymes, Marker enzymes and Tumor markers in serum and also the histopathological studies in liver is carried out in control and DEN induced rats. Supplementation of ELAS (Ethanolic Leaf Extract Of Annona squamosa) reduced the liver weight and also reduced the tumour incidence. Chemoprevention group showed near normal values of bilirubin when compared with the control rats. Total protein was decreased in the cancer bearing group and on treatment with the extract the levels of protein were restored. Both in pre and post treatment group, the activities of enzymatic antioxidants such as superoxide dismutase, catalase, and Glutathione peroxidase were increased but in pre treated animals it was more effective than post treated animals. The non- enzymatic antioxidants such as vitamin C and vitamin E were brought back to normal level significantly in post and pre treated animals. Activities of marker enzymes such as SGOT, SGPT, ALP, γ GT were significantly elevated in the serum of cancer animals and the values returned to normal after treatment with the extract suggesting the hepato protective effect of the extract. Lipid peroxide was found to be elevated in the cancer induced group. This condition was brought back to the normal in the pre and post treated animals with ELAS. Histological examination also confirmed the anti- carcinogenic potential of ELAS, Cancer induced groups had a triple fold increase in their AFP values when compared to other groups. DEN treatment increased the level of AFP expression while ELAS partially counteracted the effect of it. So the scientific validation obtained from this study may pave way to many budding scientists to find new drugs from Annona squamosa for various ailments.

Keywords: annona squamosa, biochemical parmeters, cancer, leaf extract

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269 "If It Bleeds It Leads” the Visual Witnessing Trauma Phenomenon among Journalists: An Analysis of Various Media Images from East Africa

Authors: Lydia Ouma Radoli

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The paradox of documenting history through visuals that objectify gruesome images to depict the prominence of stories intrigues media researchers. In East Africa, the topic has been captured in a variety of media frames, but scantly in scholarly work. This paper adopts Visual Rhetoric and Framing Theories to tease out the drivers behind the criteria for the selection of violent visuals. The paper projects that quantitative and qualitative literature regarding journalists’ personal and work-related exposure to PSTD will give insights into the concept of trauma journalism - reporting of horrific events, e.g., violent crime and terror. The data will be collected through methods such as document analysis (photographs and videos) and in-depth interviews to summarize the informational contents with respect to the research objectives and questions. The study is hinged on the background that the criterion for news production is constructed from the idea that ‘if there’s violence, conflict, and death involved, the story gets top priority.’ The anticipated outcome is to establish trauma experiences of visual rhetors, suggest mitigations, and address gaps in academic research. The findings of the study will sustain the critical role of visual rhetors. Further, media practitioners may find the study useful in assessing the effects and values of visual witnessing. Historically, the criterion for visual news production has been that if there’s violence, conflict, and death involved, the story gets top priority. To capture the goriness of the images, media theorists and sociologists have used the expression: “If it bleeds, it leads.” The statement assumes that audiences are attracted to pictures that show violent images. Further, research on visual aspects of Television news has shown its ability to hold viewers’ attention and cause aggression. This paper samples images and narratives from Journalists who have covered trauma-related events. The samples are indicative of the problem under study, which depicts journalists exposed to traumatic events as not receiving any Psycho-social support within newsrooms. It is hoped that the study could inform policy and practice within developing countries through the interpretations of theoretical and empirical explanations of existing trauma phenomena among journalists.

Keywords: visual-witnessing, media culture, visual rhetoric, imaging violence in East Africa

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268 Targeting Methionine Metabolism In Gastric Cancer; Promising To Improve Chemosensetivity With Non-hetrogeneity

Authors: Nigatu Tadesse, Li Juan, Liuhong Ming

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Gastric cancer (GC) is the fifth most common and fourth deadly cancer in the world with limited treatment options at late advanced stage in which surgical therapy is not recommended with chemotherapy remain as the mainstay of treatment. However, the occurrence of chemoresistance as well as intera-tumoral and inter-tumoral heterogeneity of response to targeted and immunotherapy underlined a clear unmet treatment need in gastroenterology. Several molecular and cellular alterations ascribed for chemo resistance in GC including cancer stem cells (CSC) and tumor microenvironment (TME) remodeling. Cancer cells including CSC bears higher metabolic demand and major changes in TME involves alterations of gut microbiota interacting with nutrients metabolism. Metabolic upregulation in lipids, carbohydrates, amino acids, fatty acids biosynthesis pathways identified as a common hall mark in GC. Metabolic addiction to methionine metabolism occurs in many cancer cells to promote the biosynthesis of S-Adenosylmethionine (SAM), a universal methyl donor molecule for high rate of transmethylation in GC and promote cell proliferation. Targeting methionine metabolism found to promotes chemo-sensitivity with treatment non-heterogeneity. Methionine restriction (MR) promoted the arrest of cell cycle at S/G2 phase and enhanced downregulation of GC cells resistance to apoptosis (including ferroptosis), which suggests the potential of synergy with chemotherapies acting at S-phase of the cell cycle as well as inducing cell apoptosis. Accumulated evidences showed both the biogenesis as well as intracellular metabolism of exogenous methionine could be safe and effective target for therapy either alone or in combination with chemotherapies. This review article provides an over view of the upregulation in methionine biosynthesis pathway and the molecular signaling through the PI3K/Akt/mTOR-c-MYC axis to promote metabolic reprograming through activating the expression of L-type aminoacid-1 (LAT1) transporter and overexpression of Methionine adenosyltransferase 2A(MAT2A) for intercellular metabolic conversion of exogenous methionine to SAM in GC, and the potential of targeting with novel therapeutic agents such as methioninase (METase), Methionine adenosyltransferase 2A (MAT2A), c-MYC, methyl like transferase 16 (METTL16) inhibitors that are currently under clinical trial development stages and future perspectives.

Keywords: gastric cancer, methionine metabolism, pi3k/akt/mtorc1-c-myc axis, gut microbiota, MAT2A, c-MYC, METTL16, methioninase

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267 An Indispensable Parameter in Lipid Ratios to Discriminate between Morbid Obesity and Metabolic Syndrome in Children: High Density Lipoprotein Cholesterol

Authors: Orkide Donma, Mustafa M. Donma

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Obesity is a low-grade inflammatory disease and may lead to health problems such as hypertension, dyslipidemia, diabetes. It is also associated with important risk factors for cardiovascular diseases. This requires the detailed evaluation of obesity, particularly in children. The aim of this study is to enlighten the potential associations between lipid ratios and obesity indices and to introduce those with discriminating features among children with obesity and metabolic syndrome (MetS). A total of 408 children (aged between six and eighteen years) participated in the scope of the study. Informed consent forms were taken from the participants and their parents. Ethical Committee approval was obtained. Anthropometric measurements such as weight, height as well as waist, hip, head, neck circumferences and body fat mass were taken. Systolic and diastolic blood pressure values were recorded. Body mass index (BMI), diagnostic obesity notation model assessment index-II (D2 index), waist-to-hip, head-to-neck ratios were calculated. Total cholesterol, triglycerides, high-density lipoprotein cholesterol (HDLChol), low-density lipoprotein cholesterol (LDLChol) analyses were performed in blood samples drawn from 110 children with normal body weight, 164 morbid obese (MO) children and 134 children with MetS. Age- and sex-adjusted BMI percentiles tabulated by World Health Organization were used to classify groups; normal body weight, MO and MetS. 15th-to-85th percentiles were used to define normal body weight children. Children, whose values were above the 99th percentile, were described as MO. MetS criteria were defined. Data were evaluated statistically by SPSS Version 20. The degree of statistical significance was accepted as p≤0.05. Mean±standard deviation values of BMI for normal body weight children, MO children and those with MetS were 15.7±1.1, 27.1±3.8 and 29.1±5.3 kg/m2, respectively. Corresponding values for the D2 index were calculated as 3.4±0.9, 14.3±4.9 and 16.4±6.7. Both BMI and D2 index were capable of discriminating the groups from one another (p≤0.01). As far as other obesity indices were considered, waist-to hip and head-to-neck ratios did not exhibit any statistically significant difference between MO and MetS groups (p≥0.05). Diagnostic obesity notation model assessment index-II was correlated with the triglycerides-to-HDL-C ratio in normal body weight and MO (r=0.413, p≤0.01 and r=0.261, (p≤0.05, respectively). Total cholesterol-to-HDL-C and LDL-C-to-HDL-C showed statistically significant differences between normal body weight and MO as well as MO and MetS (p≤0.05). The only group in which these two ratios were significantly correlated with waist-to-hip ratio was MetS group (r=0.332 and r=0.334, p≤0.01, respectively). Lack of correlation between the D2 index and the triglycerides-to-HDL-C ratio was another important finding in MetS group. In this study, parameters and ratios, whose associations were defined previously with increased cardiovascular risk or cardiac death have been evaluated along with obesity indices in children with morbid obesity and MetS. Their profiles during childhood have been investigated. Aside from the nature of the correlation between the D2 index and triglycerides-to-HDL-C ratio, total cholesterol-to-HDL-C as well as LDL-C-to- HDL-C ratios along with their correlations with waist-to-hip ratio showed that the combination of obesity-related parameters predicts better than one parameter and appears to be helpful for discriminating MO children from MetS group.

Keywords: children, lipid ratios, metabolic syndrome, obesity indices

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266 Cultural and Natural Heritage Conservation by GIS Tourism Inventory System Project

Authors: Gamze Safak, Umut Arslanoglu

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Cultural and tourism conservation and development zones and tourism centers are the boundaries declared for the purpose of protecting, using, and evaluating the sectoral development and planned development in areas where historical and cultural values are heavily involved and/or where tourism potential is high. The most rapidly changing regions in Turkey are tourism areas, especially the coastal areas. Planning these regions is not about only an economic gain but also a natural and physical environment and refers to a complex process. If the tourism sector is not well controlled, excessive use of natural resources and wrong location choices may cause damage to natural areas, historical values, and socio-cultural structure. Since the strategic decisions taken in the environmental order and zoning plans, which are the means of guiding the physical environment of the Ministry of Culture and Tourism, which have the authority to make plans in tourism centers, are transformed into plan decisions that find the spatial expression, comprehensive evaluation of all kinds of data, following the historical development and based on the correct and current data is required. In addition, the authority has a number of competences in tourism promotion as well as the authority to plan, leading to the necessity of taking part in the applications requiring complex analysis such as the management and integration of the country's economic, political, social and cultural resources. For this purpose, Tourism Inventory System (TES) project, which consists of a series of subsystems, has been developed in order to solve complex planning and method problems in the management of site-related information. The scope of the project is based on the integration of numerical and verbal data in the regions within the jurisdiction of the authority, and the monitoring of the historical development of urban planning studies, making the spatial data of the institution easily accessible, shared, questionable and traceable in international standards. A dynamic and continuous system design has been put into practice by utilizing the advantage of the use of Geographical Information Systems in the planning process to play a role in making the right decisions, revealing the tools of social, economic, cultural development, and preservation of natural and cultural values. This paper, which is prepared by the project team members in TES (Tourism Inventory System), will present a study regarding the applicability of GIS in cultural and natural heritage conservation.

Keywords: cultural conservation, GIS, geographic information system, tourism inventory system, urban planning

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265 The Impact of Hosting an On-Site Vocal Concert in Preschool on Music Inspiration and Learning Among Preschoolers

Authors: Meiying Liao, Poya Huang

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The aesthetic domain is one of the six major domains in the Taiwanese preschool curriculum, encompassing visual arts, music, and dramatic play. Its primary objective is to cultivate children’s abilities in exploration and awareness, expression and creation, and response and appreciation. The purpose of this study was to explore the effects of hosting a vocal music concert on aesthetic inspiration and learning among preschoolers in a preschool setting. The primary research method employed was a case study focusing on a private preschool in Northern Taiwan that organized a school-wide event featuring two vocalists. The concert repertoires included children’s songs, folk songs, and arias performed in Mandarin, Hakka, English, German, and Italian. In addition to professional performances, preschool teachers actively participated by presenting a children’s song. A total of 5 classes, comprising approximately 150 preschoolers, along with 16 teachers and staff, participated in the event. Data collection methods included observation, interviews, and documents. Results indicated that both teachers and children thoroughly enjoyed the concert, with high levels of acceptance when the program was appropriately designed and hosted. Teachers reported that post-concert discussions with children revealed the latter’s ability to recall people, events, and elements observed during the performance, expressing their impressions of the most memorable segments. The concert effectively achieved the goals of the aesthetic domain, particularly in fostering response and appreciation. It also inspired preschoolers’ interest in music. Many teachers noted an increased desire for performance among preschoolers after exposure to the concert, with children imitating the performers and their expressions. Remarkably, one class extended this experience by incorporating it into the curriculum, autonomously organizing a high-quality concert in the music learning center. Parents also reported that preschoolers enthusiastically shared their concert experiences at home. In conclusion, despite being a single event, the positive responses from preschoolers towards the music performance suggest a meaningful impact. These experiences extended into the curriculum, as firsthand exposure to performances allowed teachers to deepen related topics, fostering a habit of autonomous learning in the designated learning centers.

Keywords: concert, early childhood music education, aesthetic education, music develpment

Procedia PDF Downloads 28
264 Improving the Biocontrol of the Argentine Stem Weevil; Using the Parasitic Wasp Microctonus hyperodae

Authors: John G. Skelly, Peter K. Dearden, Thomas W. R. Harrop, Sarah N. Inwood, Joseph Guhlin

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The Argentine stem weevil (ASW; L. bonariensis) is an economically important pasture pest in New Zealand, which causes about $200 million of damage per annum. Microctonus hyperodae (Mh), a parasite of the ASW in its natural range in South America, was introduced into New Zealand to curb the pasture damage caused by the ASW. Mh is an endoparasitic wasp that lays its eggs in the ASW halting its reproduction. Mh was initially successful at preventing ASW proliferation and reducing pasture damage. The effectiveness of Mh has since declined due to decreased parasitism rates and has resulted in increased pasture damage. Although the mechanism through which ASW has developed resistance to Mh has not been discovered, it has been proposed to be due to the different reproductive modes used by Mh and the ASW in New Zealand. The ASW reproduces sexually, whereas Mh reproduces asexually, which has been hypothesised to have allowed the ASW to ‘out evolve’ Mh. Other species within the Microctonus genus reproduce both sexually and asexually. Strains of Microctonus aethiopoides (Ma), a species closely related to Mh, reproduce either by sexual or asexual reproduction. Comparing the genomes of sexual and asexual Microctonus may allow for the identification of the mechanism of asexual reproduction and other characteristics that may improve Mh as a biocontrol agent. The genomes of Mh and three strains of Ma, two of which reproduce sexually and one reproduces asexually, have been sequenced and annotated. The French (MaFR) and Moroccan (MaMO) reproduce sexually, whereas the Irish strain (MaIR) reproduces asexually. Like Mh, The Ma strains are also used as biocontrol agents, but for different weevil species. The genomes of Mh and MaIR were subsequently upgraded using Hi-C, resulting in a set of high quality, highly contiguous genomes. A subset of the genes involved in mitosis and meiosis, which have been identified though the use of Hidden Markov Models generated from genes involved in these processes in other Hymenoptera, have been catalogued in Mh and the strains of Ma. Meiosis and mitosis genes were broadly conserved in both sexual and asexual Microctonus species. This implies that either the asexual species have retained a subset of the molecular components required for sexual reproduction or that the molecular mechanisms of mitosis and meiosis are different or differently regulated in Microctonus to other insect species in which these mechanisms are more broadly characterised. Bioinformatic analysis of the chemoreceptor compliment in Microctonus has revealed some variation in the number of olfactory receptors, which may be related to host preference. Phylogenetic analysis of olfactory receptors highlights variation, which may be able to explain different host range preferences in the Microctonus. Hi-C clustering implies that Mh has 12 chromosomes, and MaIR has 8. Hence there may be variation in gene regulation between species. Genome alignment of Mh and MaIR implies that there may be large scale genome structural variation. Greater insight into the genetics of these agriculturally important group of parasitic wasps may be beneficial in restoring or maintaining their biocontrol efficacy.

Keywords: argentine stem weevil, asexual, genomics, Microctonus hyperodae

Procedia PDF Downloads 129
263 Exploring the Link between Hoarding Disorder and Trauma: A Scoping Review

Authors: Murray Anderson, Galina Freed, Karli Jahn

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Trauma is increasingly recognized as an important construct that has health implications for those who struggle with various mental health issues. For those individuals who meet the criteria for a diagnosis of hoarding disorder (HD), many have experienced some form of trauma. Further, some of the therapeutic interventions for those with HD can further perpetuate or magnify the experience of trauma. Therefore, the aim of this scoping review is to identify and document the nature and extent of research evidence related to trauma as it connects with HD. This review was guided by the questions, ‘How can our understanding of the trauma cycle help us to better appreciate the experiences of individuals who hoard, and how will a trauma informed lens inform the interventions for hoarding disorder? A comprehensive literature search was performed to identify original studies that contained the words “hoarding” and “trauma.” PsychINFO”,''EBSCO host,” “CINAHL” and “PubMed” were searched between January 2005 and April 2021. Articles were screened by three reviewers. Data extracted included publication date, demographics, study design, type of analysis, and noted connections between hoarding and trauma. Of the 329 articles, all duplicates, articles on hoardings of animals, articles not in English, and those without full-text availability were removed. Five categories were found in the remaining 45 articles, including (a) traumatic and stressful life events; (b) the link between posttraumatic stress disorder, trauma, and hoarding; (c) the relationships between different comorbidities, trauma, and hoarding; (d) the lack of early emotional expression and other forms of parental deprivation; and (e) the role of attachment. Lastly, the literature explains how the links between hoarding and trauma are difficult to study due to the highly stigmatized identities with this population. The review provided strong support for the connections between the experience of trauma and HD. What is missing from the literature is the use of a trauma-informed lens to better account for the ways in which hoarding disorder is understood. Other missing pieces in the literature are the potential uses of a trauma-informed lens to enhance the therapeutic process, to understand and reduce treatment attrition, and to improve treatment outcomes. The application of a trauma informed lens could improve our understanding of effective interactions among clients, families, and communities and improve the education around hoarding-related matters. Exploring the connections between trauma and HD can improve therapeutic delivery and destigmatize the experience of dealing with clutter and hoarding concerns. This awareness can also provide health care professionals with both the language and skills to liberate them from a reductionist view on HD.

Keywords: hoarding, attachment, parental deprivation, trauma

Procedia PDF Downloads 99
262 Density Determination of Liquid Niobium by Means of Ohmic Pulse-Heating for Critical Point Estimation

Authors: Matthias Leitner, Gernot Pottlacher

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Experimental determination of critical point data like critical temperature, critical pressure, critical volume and critical compressibility of high-melting metals such as niobium is very rare due to the outstanding experimental difficulties in reaching the necessary extreme temperature and pressure regimes. Experimental techniques to achieve such extreme conditions could be diamond anvil devices, two stage gas guns or metal samples hit by explosively accelerated flyers. Electrical pulse-heating under increased pressures would be another choice. This technique heats thin wire samples of 0.5 mm diameter and 40 mm length from room temperature to melting and then further to the end of the stable phase, the spinodal line, within several microseconds. When crossing the spinodal line, the sample explodes and reaches the gaseous phase. In our laboratory, pulse-heating experiments can be performed under variation of the ambient pressure from 1 to 5000 bar and allow a direct determination of critical point data for low-melting, but not for high-melting metals. However, the critical point also can be estimated by extrapolating the liquid phase density according to theoretical models. A reasonable prerequisite for the extrapolation is the existence of data that cover as much as possible of the liquid phase and at the same time exhibit small uncertainties. Ohmic pulse-heating was therefore applied to determine thermal volume expansion, and from that density of niobium over the entire liquid phase. As a first step, experiments under ambient pressure were performed. The second step will be to perform experiments under high-pressure conditions. During the heating process, shadow images of the expanding sample wire were captured at a frame rate of 4 × 105 fps to monitor the radial expansion as a function of time. Simultaneously, the sample radiance was measured with a pyrometer operating at a mean effective wavelength of 652 nm. To increase the accuracy of temperature deduction, spectral emittance in the liquid phase is also taken into account. Due to the high heating rates of about 2 × 108 K/s, longitudinal expansion of the wire is inhibited which implies an increased radial expansion. As a consequence, measuring the temperature dependent radial expansion is sufficient to deduce density as a function of temperature. This is accomplished by evaluating the full widths at half maximum of the cup-shaped intensity profiles that are calculated from each shadow image of the expanding wire. Relating these diameters to the diameter obtained before the pulse-heating start, the temperature dependent volume expansion is calculated. With the help of the known room-temperature density, volume expansion is then converted into density data. The so-obtained liquid density behavior is compared to existing literature data and provides another independent source of experimental data. In this work, the newly determined off-critical liquid phase density was in a second step utilized as input data for the estimation of niobium’s critical point. The approach used, heuristically takes into account the crossover from mean field to Ising behavior, as well as the non-linearity of the phase diagram’s diameter.

Keywords: critical point data, density, liquid metals, niobium, ohmic pulse-heating, volume expansion

Procedia PDF Downloads 197
261 Angiomotin Regulates Integrin Beta 1-Mediated Endothelial Cell Migration and Angiogenesis

Authors: Yuanyuan Zhang, Yujuan Zheng, Giuseppina Barutello, Sumako Kameishi, Kungchun Chiu, Katharina Hennig, Martial Balland, Federica Cavallo, Lars Holmgren

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Angiogenesis describes that new blood vessels migrate from pre-existing ones to form 3D lumenized structure and remodeling. During directional migration toward the gradient of pro-angiogenic factors, the endothelial cells, especially the tip cells need filopodia to sense the environment and exert the pulling force. Of particular interest are the integrin proteins, which play an essential role in focal adhesion in the connection between migrating cells and extracellular matrix (ECM). Understanding how these biomechanical complexes orchestrate intrinsic and extrinsic forces is important for our understanding of the underlying mechanisms driving angiogenesis. We have previously identified Angiomotin (Amot), a member of Amot scaffold protein family, as a promoter for endothelial cell migration in vitro and zebrafish models. Hence, we established inducible endothelial-specific Amot knock-out mice to study normal retinal angiogenesis as well as tumor angiogenesis. We found that the migration ratio of the blood vessel network to the edge was significantly decreased in Amotec- retinas at postnatal day 6 (P6). While almost all the Amot defect tip cells lost migration advantages at P7. In consistence with the dramatic morphology defect of tip cells, there was a non-autonomous defect in astrocytes, as well as the disorganized fibronectin expression pattern correspondingly in migration front. Furthermore, the growth of transplanted LLC tumor was inhibited in Amot knockout mice due to fewer vasculature involved. By using MMTV-PyMT transgenic mouse model, there was a significantly longer period before tumors arised when Amot was specifically knocked out in blood vessels. In vitro evidence showed that Amot binded to beta-actin, Integrin beta 1 (ITGB1), Fibronectin, FAK, Vinculin, major focal adhesion molecules, and ITGB1 and stress fibers were distinctly induced by Amot transfection. Via traction force microscopy, the total energy (force indicater) was found significantly decreased in Amot knockdown cells. Taken together, we propose that Amot is a novel partner of the ITGB1/Fibronectin protein complex at focal adhesion and required for exerting force transition between endothelial cell and extracellular matrix.

Keywords: angiogenesis, angiomotin, endothelial cell migration, focal adhesion, integrin beta 1

Procedia PDF Downloads 209
260 An Overview of Bioinformatics Methods to Detect Novel Riboswitches Highlighting the Importance of Structure Consideration

Authors: Danny Barash

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Riboswitches are RNA genetic control elements that were originally discovered in bacteria and provide a unique mechanism of gene regulation. They work without the participation of proteins and are believed to represent ancient regulatory systems in the evolutionary timescale. One of the biggest challenges in riboswitch research is that many are found in prokaryotes but only a small percentage of known riboswitches have been found in certain eukaryotic organisms. The few examples of eukaryotic riboswitches were identified using sequence-based bioinformatics search methods that include some slight structural considerations. These pattern-matching methods were the first ones to be applied for the purpose of riboswitch detection and they can also be programmed very efficiently using a data structure called affix arrays, making them suitable for genome-wide searches of riboswitch patterns. However, they are limited by their ability to detect harder to find riboswitches that deviate from the known patterns. Several methods have been developed since then to tackle this problem. The most commonly used by practitioners is Infernal that relies on Hidden Markov Models (HMMs) and Covariance Models (CMs). Profile Hidden Markov Models were also carried out in the pHMM Riboswitch Scanner web application, independently from Infernal. Other computational approaches that have been developed include RMDetect by the use of 3D structural modules and RNAbor that utilizes Boltzmann probability of structural neighbors. We have tried to incorporate more sophisticated secondary structure considerations based on RNA folding prediction using several strategies. The first idea was to utilize window-based methods in conjunction with folding predictions by energy minimization. The moving window approach is heavily geared towards secondary structure consideration relative to sequence that is treated as a constraint. However, the method cannot be used genome-wide due to its high cost because each folding prediction by energy minimization in the moving window is computationally expensive, enabling to scan only at the vicinity of genes of interest. The second idea was to remedy the inefficiency of the previous approach by constructing a pipeline that consists of inverse RNA folding considering RNA secondary structure, followed by a BLAST search that is sequence-based and highly efficient. This approach, which relies on inverse RNA folding in general and our own in-house fragment-based inverse RNA folding program called RNAfbinv in particular, shows capability to find attractive candidates that are missed by Infernal and other standard methods being used for riboswitch detection. We demonstrate attractive candidates found by both the moving-window approach and the inverse RNA folding approach performed together with BLAST. We conclude that structure-based methods like the two strategies outlined above hold considerable promise in detecting riboswitches and other conserved RNAs of functional importance in a variety of organisms.

Keywords: riboswitches, RNA folding prediction, RNA structure, structure-based methods

Procedia PDF Downloads 211
259 Plant Microbiota of Coastal Halophyte Salicornia Ramossisima

Authors: Isabel N. Sierra-Garcia, Maria J. Ferreira, Sandro Figuereido, Newton Gomes, Helena Silva, Angela Cunha

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Plant-associated microbial communities are considered crucial in the adaptation of halophytes to coastal environments. The plant microbiota can be horizontally acquired from the environment or vertically transmitted from generation to generation via seeds. Recruiting of the microbial communities by the plant is affected by geographical location, soil source, host genotype, and cultivation practice. There is limited knowledge reported on the microbial communities in halophytes the influence of biotic and abiotic factors. In this work, the microbiota associated with the halophyte Salicornia ramosissima was investigated to determine whether the structure of bacterial communities is influenced by host genotype or soil source. For this purpose, two contrasting sites where S. ramosissima is established in the estuarine system of the Ria de Aveiro were investigated. One site corresponds to a natural salt marsh where S. ramosissima plants are present (wild plants), and the other site is a former salt pan that nowadays are subjected to intensive crop production of S. ramosissima (crop plants). Bacterial communities from the rhizosphere, seeds and root endosphere of S. ramossisima from both sites were investigated by sequencing bacterial 16S rRNA gene using the Illumina MiSeq platform. The analysis of the sequences showed that the three plant-associated compartments, rhizosphere, root endosphere, and seed endosphere, harbor distinct microbiomes. However, bacterial richness and diversity were higher in seeds of wild plants, followed by rhizosphere in both sites, while seeds in the crop site had the lowest diversity. Beta diversity measures indicated that bacterial communities in root endosphere and seeds were more similar in both wild and crop plants in contrast to rhizospheres that differed by local, indicating that the recruitment of the similar bacterial communities by the plant genotype is active in regard to the site. Moreover, bacterial communities from the root endosphere and rhizosphere were phylogenetically more similar in both sites, but the phylogenetic composition of seeds in wild and crop sites was distinct. These results indicate that cultivation practices affect the seed microbiome. However, minimal vertical transmission of bacteria from seeds to adult plants is expected. Seeds from the crop site showed higher abundances of Kushneria and Zunongwangia genera. Bacterial members of the classes Alphaprotebacteria and Bacteroidia were the most ubiquitous across sites and compartments and might encompass members of the core microbiome. These findings indicate that bacterial communities associated with S. ramosissima are more influenced by host genotype rather than local abiotic factors or cultivation practices. This study provides a better understanding of the composition of the plant microbiota in S. ramosissima , which is essential to predict the interactions between plant and associated microbial communities and their effects on plant health. This knowledge is useful to the manipulations of these microbial communities to enhance the health and productivity of this commercially important plant.

Keywords: halophytes, plant microbiome, Salicornia ramosissima, agriculture

Procedia PDF Downloads 134
258 Charged Amphiphilic Polypeptide Based Micelle Hydrogel Composite for Dual Drug Release

Authors: Monika Patel, Kazuaki Matsumura

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Synthetic hydrogels, with their unique properties such as porosity, strength, and swelling in aqueous environment, are being used in many fields from food additives to regenerative medicines, from diagnostic and pharmaceuticals to drug delivery systems (DDS). But, hydrogels also have some limitations in terms of homogeneity of drug distribution and quantity of loaded drugs. As an alternate, polymeric micelles are extensively used as DDS. With the ease of self-assembly, and distinct stability they remarkably improve the solubility of hydrophobic drugs. However, presently, combinational therapy is the need of time and so are systems which are capable of releasing more than one drug. And it is one of the major challenges towards DDS to control the release of each drug independently, which simple DDS cannot meet. In this work, we present an amphiphilic polypeptide based micelle hydrogel composite to study the dual drug release for wound healing purposes using Amphotericin B (AmpB) and Curcumin as model drugs. Firstly, two differently charged amphiphilic polypeptide chains were prepared namely, poly L-Lysine-b-poly phenyl alanine (PLL-PPA) and poly Glutamic acid-b-poly phenyl alanine (PGA-PPA) through ring opening polymerization of amino acid N-carboxyanhydride. These polymers readily self-assemble to form micelles with hydrophobic PPA block as core and hydrophilic PLL/PGA as shell with an average diameter of about 280nm. The thus formed micelles were loaded with the model drugs. The PLL-PPA micelle was loaded with curcumin and PGA-PPA was loaded with AmpB by dialysis method. Drug loaded micelles showed a slight increase in the mean diameter and were fairly stable in solution and lyophilized forms. For forming the micelles hydrogel composite, the drug loaded micelles were dissolved and were cross linked using genipin. Genipin uses the free –NH2 groups in the PLL-PPA micelles to form a hydrogel network with free PGA-PPA micelles trapped in between the 3D scaffold formed. Different composites were tested by changing the weight ratios of the both micelles and were seen to alter its resulting surface charge from positive to negative with increase in PGA-PPA ratio. The composites with high surface charge showed a burst release of drug in initial phase, were as the composites with relatively low net charge showed a sustained release. Thus the resultant surface charge of the composite can be tuned to tune its drug release profile. Also, while studying the degree of cross linking among the PLL-PPA particles for effect on dual drug release, it was seen that as the degree of crosslinking increases, an increase in the tendency to burst release the drug (AmpB) is seen in PGA-PPA particle, were as on the contrary the PLL-PPA particles showed a slower release of Curcumin with increasing the cross linking density. Thus, two different pharmacokinetic profile of drugs were seen by changing the cross linking degree. In conclusion, a unique charged amphiphilic polypeptide based micelle hydrogel composite for dual drug delivery. This composite can be finely tuned on the basis of need of drug release profiles by changing simple parameters such as composition, cross linking and pH.

Keywords: amphiphilic polypeptide, dual drug release, micelle hydrogel composite, tunable DDS

Procedia PDF Downloads 181
257 Analysis of Flow Dynamics of Heated and Cooled Pylon Upstream to the Cavity past Supersonic Flow with Wall Heating and Cooling

Authors: Vishnu Asokan, Zaid M. Paloba

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Flow over cavities is an important area of research due to the significant change in flow physics caused by cavity aspect ratio, free stream Mach number and the nature of upstream boundary layer approaching the cavity leading edge. Cavity flow finds application in aircraft wheel well, weapons bay, combustion chamber of scramjet engines, etc. These flows are highly unsteady, compressible and turbulent and it involves mass entrainment coupled with acoustics phenomenon. Variation of flow dynamics in an angled cavity with a heated and cooled pylon upstream to the cavity with spatial combinations of heat flux addition and removal to the wall studied numerically. The goal of study is to investigate the effect of energy addition, removal to the cavity walls and pylon cavity flow dynamics. Preliminary steady state numerical simulations on inclined cavities with heat addition have shown that wall pressure profiles, as well as the recirculation, are influenced by heat transfer to the compressible fluid medium. Such a hybrid control of cavity flow dynamics in the form of heat transfer and pylon geometry can open out greater opportunities in enhancement of mixing and flame holding requirements of supersonic combustors. Addition of pylon upstream to the cavity reduces the acoustic oscillations emanating from the geometry. A numerical unsteady analysis of supersonic flow past cavities exposed to cavity wall heating and cooling with heated and cooled pylon helps to get a clear idea about the oscillation suppression in the cavity. A Cavity of L/D 4 and aft wall angle 22 degree with an upstream pylon of h/D=1.5 mm with a wall angle 29 degree exposed to supersonic flow of Mach number 2 and heat flux of 40 W/cm² and -40 W/cm² modeled for the above study. In the preliminary study, the domain is modeled and validated numerically with a turbulence model of SST k-ω using an HLLC implicit scheme. Both qualitative and quantitative flow data extracted and analyzed using advanced CFD tools. Flow visualization is done using numerical Schlieren method as the fluid medium gives the density variation. The heat flux addition to the wall increases the secondary vortex size of the cavity and removal of energy leads to the reduction in vortex size. The flow field turbulence seems to be increasing at higher heat flux. The shear layer thickness increases as heat flux increases. The steady state analysis of wall pressure shows that there is variation on wall pressure as heat flux increases. Shift in frequency of unsteady wall pressure analysis is an interesting observation for the above study. The time averaged skin friction seems to be reducing at higher heat flux due to the variation in viscosity of fluid inside the cavity.

Keywords: energy addition, frequency shift, Numerical Schlieren, shear layer, vortex evolution

Procedia PDF Downloads 120
256 Constructivist Grounded Theory of Intercultural Learning

Authors: Vaida Jurgile

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Intercultural learning is one of the approaches taken to understand the cultural diversity of the modern world and to accept changes in cultural identity and otherness and the expression of tolerance. During intercultural learning, students develop their abilities to interact and communicate with their group members. These abilities help to understand social and cultural differences, to form one’s identity, and to give meaning to intercultural learning. Intercultural education recognizes that a true understanding of differences and similarities of another culture is necessary in order to lay the foundations for working together with others, which contributes to the promotion of intercultural dialogue, appreciation of diversity, and cultural exchange. Therefore, it is important to examine the concept of intercultural learning, revealed through students’ learning experiences and understanding of how this learning takes place and what significance this phenomenon has in higher education. At a scientific level, intercultural learning should be explored in order to uncover the influence of cultural identity, i.e., intercultural learning should be seen in a local context. This experience would provide an opportunity to learn from various everyday intercultural learning situations. Intercultural learning can be not only a form of learning but also a tool for building understanding between people of different cultures. The research object of the study is the process of intercultural learning. The aim of the dissertation is to develop a grounded theory of the process of learning in an intercultural study environment, revealing students’ learning experiences. The research strategy chosen in this study is a constructivist grounded theory (GT). GT is an inductive method that seeks to form a theory by applying the systematic collection, synthesis, analysis, and conceptualization of data. The targeted data collection was based on the analysis of data provided by previous research participants, which revealed the need for further research participants. During the research, only students with at least half a year of study experience, i.e., who have completed at least one semester of intercultural studies, were purposefully selected for the research. To select students, snowballing sampling was used. 18 interviews were conducted with students representing 3 different fields of sciences (social sciences, humanities, and technology sciences). In the process of intercultural learning, language expresses and embodies cultural reality and a person’s cultural identity. It is through language that individual experiences are expressed, and the world in which Others exist is perceived. The increased emphasis is placed on the fact that language conveys certain “signs’ of communication and perception with cultural value, enabling the students to identify the Self and the Other. Language becomes an important tool in the process of intercultural communication because it is only through language that learners can communicate, exchange information, and understand each other. Thus, in the process of intercultural learning, language either promotes interpersonal relationships with foreign students or leads to mutual rejection.

Keywords: intercultural learning, grounded theory, students, other

Procedia PDF Downloads 33
255 Train Timetable Rescheduling Using Sensitivity Analysis: Application of Sobol, Based on Dynamic Multiphysics Simulation of Railway Systems

Authors: Soha Saad, Jean Bigeon, Florence Ossart, Etienne Sourdille

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Developing better solutions for train rescheduling problems has been drawing the attention of researchers for decades. Most researches in this field deal with minor incidents that affect a large number of trains due to cascading effects. They focus on timetables, rolling stock and crew duties, but do not take into account infrastructure limits. The present work addresses electric infrastructure incidents that limit the power available for train traction, and hence the transportation capacity of the railway system. Rescheduling is needed in order to optimally share the available power among the different trains. We propose a rescheduling process based on dynamic multiphysics railway simulations that include the mechanical and electrical properties of all the system components and calculate physical quantities such as the train speed profiles, voltage along the catenary lines, temperatures, etc. The optimization problem to solve has a large number of continuous and discrete variables, several output constraints due to physical limitations of the system, and a high computation cost. Our approach includes a phase of sensitivity analysis in order to analyze the behavior of the system and help the decision making process and/or more precise optimization. This approach is a quantitative method based on simulation statistics of the dynamic railway system, considering a predefined range of variation of the input parameters. Three important settings are defined. Factor prioritization detects the input variables that contribute the most to the outputs variation. Then, factor fixing allows calibrating the input variables which do not influence the outputs. Lastly, factor mapping is used to study which ranges of input values lead to model realizations that correspond to feasible solutions according to defined criteria or objectives. Generalized Sobol indexes are used for factor prioritization and factor fixing. The approach is tested in the case of a simple railway system, with a nominal traffic running on a single track line. The considered incident is the loss of a feeding power substation, which limits the power available and the train speed. Rescheduling is needed and the variables to be adjusted are the trains departure times, train speed reduction at a given position and the number of trains (cancellation of some trains if needed). The results show that the spacing between train departure times is the most critical variable, contributing to more than 50% of the variation of the model outputs. In addition, we identify the reduced range of variation of this variable which guarantees that the output constraints are respected. Optimal solutions are extracted, according to different potential objectives: minimizing the traveling time, the train delays, the traction energy, etc. Pareto front is also built.

Keywords: optimization, rescheduling, railway system, sensitivity analysis, train timetable

Procedia PDF Downloads 379
254 The Positive Effects of Top-Sharing: A Case Study

Authors: Maike Andresen, Georg Dochtmann

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Due to political, social, and societal changes in labor organization, top-sharing, defined as job-sharing in leading positions, becomes more important in HRM. German companies are looking for practical and economically meaningful solutions that allow to enduringly increase women’s ratio in management, not only because of a recently implemented quota. Furthermore, supporting employees in achieving work-life balance is perceived as an important goal for a sustainable HRM to gain competitive advantage. Top-sharing is seen as being suitable to reach both goals. To evaluate determinants leading to effective top-sharing, a case study of a newly implemented top-sharing tandem in a large German enterprise was conducted over a period of 15 months. In this company, a full leadership position was split into two 60%-part-time positions held by an experienced female leader in her late career and a female college who took over her first leadership position (mid-career). We assumed a person-person fit in terms of a match of the top sharing partners’ personality profiles (Big Five) and their leadership motivations to be important prerequisites for an effective collaboration between them. We evaluated the person-person fit variables once before the tandem started to work. Both leaders were expected to learn from each other (mentoring, competency development). On an operational level, they were supposed to lead together the same employees in an effective manner (leader-member exchange), presupposing an effective cooperation between both (handing over information). To see developments over time, these processes were evaluated three times over the span of the project. Top-Sharing and the underlined processes are expected to positively influence the tandem’s performance which has been evaluated twice, at the beginning and the end of the project, to assess its development over time as well. The evaluation of the personality and the basic motives suggests that both executives can be a successful top-sharing tandem. The competency evaluations (supervisor as well as self-assessment) increased over the time span. Although the top sharing tandem worked on equal terms, they implemented rather classical than peer-mentoring due to different career ambitions of the tandem partners. Thus, opportunities were not used completely. Team-member exchange scores proved the good cooperation between the top-sharers. Although the employees did not evaluate the leader-member-exchange between them and the two leaders of the tandem homogeneously, the top-sharing tandem itself did not have the impression that the employees’ task performance depended on whom of the tandem was responsible for the task. Furthermore, top-sharing did not negatively influence the performance of both leaders. During qualitative interviews with the top-sharers and their team, we found that the top-sharers could focus more easily on their tasks. The results suggest positive outcomes of top-sharing (e.g. competency improvement, learning from each other through mentoring). Top-Sharing does not hamper performance. Thus, further research and practical implementations are suggested. As part-time jobs are still more often a female solution to increase their work-life- and work-family-balance, top-sharing may be a suitable solution to increase the woman’s ratio in leadership positions as well as to sustainable increase work-life-balance of executives.

Keywords: mentoring, part-time leadership, top-sharing, work-life-balance

Procedia PDF Downloads 241
253 Design, Development and Testing of Polymer-Glass Microfluidic Chips for Electrophoretic Analysis of Biological Sample

Authors: Yana Posmitnaya, Galina Rudnitskaya, Tatyana Lukashenko, Anton Bukatin, Anatoly Evstrapov

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An important area of biological and medical research is the study of genetic mutations and polymorphisms that can alter gene function and cause inherited diseases and other diseases. The following methods to analyse DNA fragments are used: capillary electrophoresis and electrophoresis on microfluidic chip (MFC), mass spectrometry with electrophoresis on MFC, hybridization assay on microarray. Electrophoresis on MFC allows to analyse small volumes of samples with high speed and throughput. A soft lithography in polydimethylsiloxane (PDMS) was chosen for operative fabrication of MFCs. A master-form from silicon and photoresist SU-8 2025 (MicroChem Corp.) was created for the formation of micro-sized structures in PDMS. A universal topology which combines T-injector and simple cross was selected for the electrophoretic separation of the sample. Glass K8 and PDMS Sylgard® 184 (Dow Corning Corp.) were used for fabrication of MFCs. Electroosmotic flow (EOF) plays an important role in the electrophoretic separation of the sample. Therefore, the estimate of the quantity of EOF and the ways of its regulation are of interest for the development of the new methods of the electrophoretic separation of biomolecules. The following methods of surface modification were chosen to change EOF: high-frequency (13.56 MHz) plasma treatment in oxygen and argon at low pressure (1 mbar); 1% aqueous solution of polyvinyl alcohol; 3% aqueous solution of Kolliphor® P 188 (Sigma-Aldrich Corp.). The electroosmotic mobility was evaluated by the method of Huang X. et al., wherein the borate buffer was used. The influence of physical and chemical methods of treatment on the wetting properties of the PDMS surface was controlled by the sessile drop method. The most effective way of surface modification of MFCs, from the standpoint of obtaining the smallest value of the contact angle and the smallest value of the EOF, was the processing with aqueous solution of Kolliphor® P 188. This method of modification has been selected for the treatment of channels of MFCs, which are used for the separation of mixture of oligonucleotides fluorescently labeled with the length of chain with 10, 20, 30, 40 and 50 nucleotides. Electrophoresis was performed on the device MFAS-01 (IAI RAS, Russia) at the separation voltage of 1500 V. 6% solution of polydimethylacrylamide with the addition of 7M carbamide was used as the separation medium. The separation time of components of the mixture was determined from electropherograms. The time for untreated MFC was ~275 s, and for the ones treated with solution of Kolliphor® P 188 – ~ 220 s. Research of physical-chemical methods of surface modification of MFCs allowed to choose the most effective way for reducing EOF – the modification with aqueous solution of Kolliphor® P 188. In this case, the separation time of the mixture of oligonucleotides decreased about 20%. The further optimization of method of modification of channels of MFCs will allow decreasing the separation time of sample and increasing the throughput of analysis.

Keywords: electrophoresis, microfluidic chip, modification, nucleic acid, polydimethylsiloxane, soft lithography

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252 Predicting Food Waste and Losses Reduction for Fresh Products in Modified Atmosphere Packaging

Authors: Matar Celine, Gaucel Sebastien, Gontard Nathalie, Guilbert Stephane, Guillard Valerie

Abstract:

To increase the very short shelf life of fresh fruits and vegetable, Modified Atmosphere Packaging (MAP) allows an optimal atmosphere composition to be maintained around the product and thus prevent its decay. This technology relies on the modification of internal packaging atmosphere due to equilibrium between production/consumption of gases by the respiring product and gas permeation through the packaging material. While, to the best of our knowledge, benefit of MAP for fresh fruits and vegetable has been widely demonstrated in the literature, its effect on shelf life increase has never been quantified and formalized in a clear and simple manner leading difficult to anticipate its economic and environmental benefit, notably through the decrease of food losses. Mathematical modelling of mass transfers in the food/packaging system is the basis for a better design and dimensioning of the food packaging system. But up to now, existing models did not permit to estimate food quality nor shelf life gain reached by using MAP. However, shelf life prediction is an indispensable prerequisite for quantifying the effect of MAP on food losses reduction. The objective of this work is to propose an innovative approach to predict shelf life of MAP food product and then to link it to a reduction of food losses and wastes. In this purpose, a ‘Virtual MAP modeling tool’ was developed by coupling a new predictive deterioration model (based on visual surface prediction of deterioration encompassing colour, texture and spoilage development) with models of the literature for respiration and permeation. A major input of this modelling tool is the maximal percentage of deterioration (MAD) which was assessed from dedicated consumers’ studies. Strawberries of the variety Charlotte were selected as the model food for its high perishability, high respiration rate; 50-100 ml CO₂/h/kg produced at 20°C, allowing it to be a good representative of challenging post-harvest storage. A value of 13% was determined as a limit of acceptability for the consumers, permitting to define products’ shelf life. The ‘Virtual MAP modeling tool’ was validated in isothermal conditions (5, 10 and 20°C) and in dynamic temperature conditions mimicking commercial post-harvest storage of strawberries. RMSE values were systematically lower than 3% for respectively, O₂, CO₂ and deterioration profiles as a function of time confirming the goodness of model fitting. For the investigated temperature profile, a shelf life gain of 0.33 days was obtained in MAP compared to the conventional storage situation (no MAP condition). Shelf life gain of more than 1 day could be obtained for optimized post-harvest conditions as numerically investigated. Such shelf life gain permitted to anticipate a significant reduction of food losses at the distribution and consumer steps. This food losses' reduction as a function of shelf life gain has been quantified using a dedicated mathematical equation that has been developed for this purpose.

Keywords: food losses and wastes, modified atmosphere packaging, mathematical modeling, shelf life prediction

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251 Evaluation of Herbal Extracts for Their Potential Application as Skin Prebiotics

Authors: Anja I. Petrov, Milica B. Veljković, Marija M. Ćorović, Ana D. Milivojević, Milica B. Simović, Katarina M. Banjanac, Dejan I. Bezbradica

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One of the fundamental requirements for overall human well-being is a stable and balanced microbiome. Aside from the microorganisms that reside within the body, a large number of microorganisms, especially bacteria, swarming the human skin is in homeostasis with the host and represents a skin microbiota. Even though the immune system of the skin is capable of distinguishing between commensal and potentially harmful transient bacteria, the cutaneous microbial balance can be disrupted under certain circumstances. In that case, a reduction in the skin microbiota diversity, as well as changes in metabolic activity, results in dermal infections and inflammation. Probiotics and prebiotics have the potential to play a significant role in the treatment of these skin disorders. The most common resident bacteria found on the skin, Staphylococcus epidermidis, can act as a potential skin probiotic, contributing to the protection of healthy skin from pathogen colonization, such as Staphylococcus aureus, which is related to atopic dermatitis exacerbation. However, as it is difficult to meet regulations in cosmetic products, another therapy approach could be topical prebiotic supplementation of the skin microbiota. In recent research, polyphenols are attracting scientists' interest as biomolecules with possible prebiotic effects on the skin microbiota. This research aimed to determine how herbal extracts rich in different polyphenolic compounds (lemon balm, St. John's wort, coltsfoot, pine needle, and yarrow) affected the growth of S. epidermidis and S. aureus. The first part of the study involved screening plants to determine if they could be regarded as probable candidates to be skin prebiotics. The effect of each plant on bacterial growth was examined by supplementing the nutrient medium with their extracts and comparing it with control samples (without extract). The results obtained after 24 h of incubation showed that all tested extracts influenced the growth of the examined bacteria to some extent. Since lemon balm and St. John's wort extracts displayed bactericidal activity against S. epidermidis, whereas coltsfoot inhibited both bacteria equally, they were not explored further. On the other hand, pine needles and yarrow extract led to an increase in S. epidermidis/S. aureus ratio, making them prospective candidates to be used as skin prebiotics. By examining the prebiotic effect of two extracts at different concentrations, it was revealed that, in the case of yarrow, 0.1% of extract dry matter in the fermentation medium was optimal, while for the pine needle extract, a concentration of 0.05% was preferred, since it selectively stimulated S. epidermidis growth and inhibited S. aureus proliferation. Additionally, the total polyphenols and flavonoid content of the two extracts were determined, revealing different concentrations and polyphenol profiles. Since yarrow and pine extracts affected the growth of skin bacteria in a dose-dependent manner, by carefully selecting the quantities of these extracts, and thus polyphenols content, it is possible to achieve desirable alterations of skin microbiota composition, which may be suitable for the treatment of atopic dermatitis.

Keywords: herbal extracts, polyphenols, skin microbiota, skin prebiotics

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250 Developing a Deep Understanding of the Immune Response in Hepatitis B Virus Infected Patients Using a Knowledge Driven Approach

Authors: Hanan Begali, Shahi Dost, Annett Ziegler, Markus Cornberg, Maria-Esther Vidal, Anke R. M. Kraft

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Chronic hepatitis B virus (HBV) infection can be treated with nucleot(s)ide analog (NA), for example, which inhibits HBV replication. However, they have hardly any influence on the functional cure of HBV, which is defined by hepatitis B surface antigen (HBsAg) loss. NA needs to be taken life-long, which is not available for all patients worldwide. Additionally, NA-treated patients are still at risk of developing cirrhosis, liver failure, or hepatocellular carcinoma (HCC). Although each patient has the same components of the immune system, immune responses vary between patients. Therefore, a deeper understanding of the immune response against HBV in different patients is necessary to understand the parameters leading to HBV cure and to use this knowledge to optimize HBV therapies. This requires seamless integration of an enormous amount of diverse and fine-grained data from viral markers, e.g., hepatitis B core-related antigen (HBcrAg) and hepatitis B surface antigen (HBsAg). The data integration system relies on the assumption that profiling human immune systems requires the analysis of various variables (e.g., demographic data, treatments, pre-existing conditions, immune cell response, or HLA-typing) rather than only one. However, the values of these variables are collected independently. They are presented in a myriad of formats, e.g., excel files, textual descriptions, lab book notes, and images of flow cytometry dot plots. Additionally, patients can be identified differently in these analyses. This heterogeneity complicates the integration of variables, as data management techniques are needed to create a unified view in which individual formats and identifiers are transparent when profiling the human immune systems. The proposed study (HBsRE) aims at integrating heterogeneous data sets of 87 chronically HBV-infected patients, e.g., clinical data, immune cell response, and HLA-typing, with knowledge encoded in biomedical ontologies and open-source databases into a knowledge-driven framework. This new technique enables us to harmonize and standardize heterogeneous datasets in the defined modeling of the data integration system, which will be evaluated in the knowledge graph (KG). KGs are data structures that represent the knowledge and data as factual statements using a graph data model. Finally, the analytic data model will be applied on top of KG in order to develop a deeper understanding of the immune profiles among various patients and to evaluate factors playing a role in a holistic profile of patients with HBsAg level loss. Additionally, our objective is to utilize this unified approach to stratify patients for new effective treatments. This study is developed in the context of the project “Transforming big data into knowledge: for deep immune profiling in vaccination, infectious diseases, and transplantation (ImProVIT)”, which is a multidisciplinary team composed of computer scientists, infection biologists, and immunologists.

Keywords: chronic hepatitis B infection, immune response, knowledge graphs, ontology

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249 Re-interpreting Ruskin with Respect to the Wall

Authors: Anjali Sadanand, R. V. Nagarajan

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Architecture morphs with advances in technology and the roof, wall, and floor as basic elements of a building, follow in redefining themselves over time. Their contribution is bound by time and held by design principles that deal with function, sturdiness, and beauty. Architecture engages with people to give joy through its form, material, design structure, and spatial qualities. This paper attempts to re-interpret John Ruskin’s “Seven lamps of Architecture” in the context of the architecture of the modern and present period. The paper focuses on the “wall” as an element of study in this context. Four of Ruskin’s seven lamps will be discussed, namely beauty, truth, life, and memory, through examples of architecture ranging from modernism to contemporary architecture of today. The study will focus on the relevance of Ruskin’s principles to the “wall” in specific, in buildings of different materials and over a range of typologies from all parts of the world. Two examples will be analyzed for each lamp. It will be shown that in each case, there is relevance to the significance of Ruskin’s lamps in modern and contemporary architecture. Nature to which Ruskin alludes to for his lamp of “beauty” is found in the different expressions of interpretation used by Corbusier in his Villa Stein façade based on proportion found in nature and in the direct expression of Toyo Ito in his translation of an understanding of the structure of trees into his façade design of the showroom for a Japanese bag boutique. “Truth” is shown in Mies van der Rohe’s Crown Hall building with its clarity of material and structure and Studio Mumbai’s Palmyra House, which celebrates the use of natural materials and local craftsmanship. “Life” is reviewed with a sustainable house in Kerala by Ashrams Ravi and Alvar Aalto’s summer house, which illustrate walls as repositories of intellectual thought and craft. “Memory” is discussed with Charles Correa’s Jawahar Kala Kendra and Venturi’s Vana Venturi house and discloses facades as text in the context of its materiality and iconography. Beauty is reviewed in Villa Stein and Toyo Ito’s Branded Retail building in Tokyo. The paper thus concludes that Ruskin’s Lamps can be interpreted in today’s context and add richness to meaning to the understanding of architecture.

Keywords: beauty, design, facade, modernism

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248 Identification of Potent and Selective SIRT7 Anti-Cancer Inhibitor via Structure-Based Virtual Screening and Molecular Dynamics Simulation

Authors: Md. Fazlul Karim, Ashik Sharfaraz, Aysha Ferdoushi

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Background: Computational medicinal chemistry approaches are used for designing and identifying new drug-like molecules, predicting properties and pharmacological activities, and optimizing lead compounds in drug development. SIRT7, a nicotinamide adenine dinucleotide (NAD+)-dependent deacylase which regulates aging, is an emerging target for cancer therapy with mounting evidence that SIRT7 downregulation plays important roles in reversing cancer phenotypes and suppressing tumor growth. Activation or altered expression of SIRT7 is associated with the progression and invasion of various cancers, including liver, breast, gastric, prostate, and non-small cell lung cancer. Objectives: The goal of this work was to identify potent and selective bioactive candidate inhibitors of SIRT7 by in silico screening of small molecule compounds obtained from Nigella sativa (N. sativa). Methods: SIRT7 structure was retrieved from The Research Collaboratory for Structural Bioinformatics Protein Data Bank (RCSB PDB), and its active site was identified using CASTp and metaPocket. Molecular docking simulation was performed with PyRx 0.8 virtual screening software. Drug-likeness properties were tested using SwissADME and pkCSM. In silico toxicity was evaluated by Osiris Property Explorer. Bioactivity was predicted by Molinspiration software. Antitumor activity was screened for Prediction of Activity Spectra for Substances (PASS) using Way2Drug web server. Molecular dynamics (MD) simulation was carried out by Desmond v3.6 package. Results: A total of 159 bioactive compounds from the N. Sativa were screened against the SIRT7 enzyme. Five bioactive compounds: chrysin (CID:5281607), pinocembrin (CID:68071), nigellidine (CID:136828302), nigellicine (CID:11402337), and epicatechin (CID:72276) were identified as potent SIRT7 anti-cancer candidates after docking score evaluation and applying Lipinski's Rule of Five. Finally, MD simulation identified Chrysin as the top SIRT7 anti-cancer candidate molecule. Conclusion: Chrysin, which shows a potential inhibitory effect against SIRT7, can act as a possible anti-cancer drug candidate. This inhibitor warrants further evaluation to check its pharmacokinetics and pharmacodynamics properties both in vitro and in vivo.

Keywords: SIRT7, antitumor, molecular docking, molecular dynamics simulation

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