Search results for: presence metrics
Commenced in January 2007
Frequency: Monthly
Edition: International
Paper Count: 5380

Search results for: presence metrics

100 A Single Cell Omics Experiments as Tool for Benchmarking Bioinformatics Oncology Data Analysis Tools

Authors: Maddalena Arigoni, Maria Luisa Ratto, Raffaele A. Calogero, Luca Alessandri

Abstract:

The presence of tumor heterogeneity, where distinct cancer cells exhibit diverse morphological and phenotypic profiles, including gene expression, metabolism, and proliferation, poses challenges for molecular prognostic markers and patient classification for targeted therapies. Understanding the causes and progression of cancer requires research efforts aimed at characterizing heterogeneity, which can be facilitated by evolving single-cell sequencing technologies. However, analyzing single-cell data necessitates computational methods that often lack objective validation. Therefore, the establishment of benchmarking datasets is necessary to provide a controlled environment for validating bioinformatics tools in the field of single-cell oncology. Benchmarking bioinformatics tools for single-cell experiments can be costly due to the high expense involved. Therefore, datasets used for benchmarking are typically sourced from publicly available experiments, which often lack a comprehensive cell annotation. This limitation can affect the accuracy and effectiveness of such experiments as benchmarking tools. To address this issue, we introduce omics benchmark experiments designed to evaluate bioinformatics tools to depict the heterogeneity in single-cell tumor experiments. We conducted single-cell RNA sequencing on six lung cancer tumor cell lines that display resistant clones upon treatment of EGFR mutated tumors and are characterized by driver genes, namely ROS1, ALK, HER2, MET, KRAS, and BRAF. These driver genes are associated with downstream networks controlled by EGFR mutations, such as JAK-STAT, PI3K-AKT-mTOR, and MEK-ERK. The experiment also featured an EGFR-mutated cell line. Using 10XGenomics platform with cellplex technology, we analyzed the seven cell lines together with a pseudo-immunological microenvironment consisting of PBMC cells labeled with the Biolegend TotalSeq™-B Human Universal Cocktail (CITEseq). This technology allowed for independent labeling of each cell line and single-cell analysis of the pooled seven cell lines and the pseudo-microenvironment. The data generated from the aforementioned experiments are available as part of an online tool, which allows users to define cell heterogeneity and generates count tables as an output. The tool provides the cell line derivation for each cell and cell annotations for the pseudo-microenvironment based on CITEseq data by an experienced immunologist. Additionally, we created a range of pseudo-tumor tissues using different ratios of the aforementioned cells embedded in matrigel. These tissues were analyzed using 10XGenomics (FFPE samples) and Curio Bioscience (fresh frozen samples) platforms for spatial transcriptomics, further expanding the scope of our benchmark experiments. The benchmark experiments we conducted provide a unique opportunity to evaluate the performance of bioinformatics tools for detecting and characterizing tumor heterogeneity at the single-cell level. Overall, our experiments provide a controlled and standardized environment for assessing the accuracy and robustness of bioinformatics tools for studying tumor heterogeneity at the single-cell level, which can ultimately lead to more precise and effective cancer diagnosis and treatment.

Keywords: single cell omics, benchmark, spatial transcriptomics, CITEseq

Procedia PDF Downloads 90
99 Prospective Museum Visitor Management Based on Prospect Theory: A Pragmatic Approach

Authors: Athina Thanou, Eirini Eleni Tsiropoulou, Symeon Papavassiliou

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The problem of museum visitor experience and congestion management – in various forms - has come increasingly under the spotlight over the last few years, since overcrowding can significantly decrease the quality of visitors’ experience. Evidence suggests that on busy days the amount of time a visitor spends inside a crowded house museum can fall by up to 60% compared to a quiet mid-week day. In this paper we consider the aforementioned problem, by treating museums as evolving social systems that induce constraints. However, in a cultural heritage space, as opposed to the majority of social environments, the momentum of the experience is primarily controlled by the visitor himself. Visitors typically behave selfishly regarding the maximization of their own Quality of Experience (QoE) - commonly expressed through a utility function that takes several parameters into consideration, with crowd density and waiting/visiting time being among the key ones. In such a setting, congestion occurs when either the utility of one visitor decreases due to the behavior of other persons, or when costs of undertaking an activity rise due to the presence of other persons. We initially investigate how visitors’ behavioral risk attitudes, as captured and represented by prospect theory, affect their decisions in resource sharing settings, where visitors’ decisions and experiences are strongly interdependent. Different from the majority of existing studies and literature, we highlight that visitors are not risk neutral utility maximizers, but they demonstrate risk-aware behavior according to their personal risk characteristics. In our work, exhibits are organized into two groups: a) “safe exhibits” that correspond to less congested ones, where the visitors receive guaranteed satisfaction in accordance with the visiting time invested, and b) common pool of resources (CPR) exhibits, which are the most popular exhibits with possibly increased congestion and uncertain outcome in terms of visitor satisfaction. A key difference is that the visitor satisfaction due to CPR strongly depends not only on the invested time decision of a specific visitor, but also on that of the rest of the visitors. In the latter case, the over-investment in time, or equivalently the increased congestion potentially leads to “exhibit failure”, interpreted as the visitors gain no satisfaction from their observation of this exhibit due to high congestion. We present a framework where each visitor in a distributed manner determines his time investment in safe or CPR exhibits to optimize his QoE. Based on this framework, we analyze and evaluate how visitors, acting as prospect-theoretic decision-makers, respond and react to the various pricing policies imposed by the museum curators. Based on detailed evaluation results and experiments, we present interesting observations, regarding the impact of several parameters and characteristics such as visitor heterogeneity and use of alternative pricing policies, on scalability, user satisfaction, museum capacity, resource fragility, and operation point stability. Furthermore, we study and present the effectiveness of alternative pricing mechanisms, when used as implicit tools, to deal with the congestion management problem in the museums, and potentially decrease the exhibit failure probability (fragility), while considering the visitor risk preferences.

Keywords: museum resource and visitor management, congestion management, propsect theory, cyber physical social systems

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98 Analysis of Potential Associations of Single Nucleotide Polymorphisms in Patients with Schizophrenia Spectrum Disorders

Authors: Tatiana Butkova, Nikolai Kibrik, Kristina Malsagova, Alexander Izotov, Alexander Stepanov, Anna Kaysheva

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Relevance. The genetic risk of developing schizophrenia is determined by two factors: single nucleotide polymorphisms and gene copy number variations. The search for serological markers for early diagnosis of schizophrenia is driven by the fact that the first five years of the disease are accompanied by significant biological, psychological, and social changes. It is during this period that pathological processes are most amenable to correction. The aim of this study was to analyze single nucleotide polymorphisms (SNPs) that are hypothesized to potentially influence the onset and development of the endogenous process. Materials and Methods It was analyzed 73 single nucleotide polymorphism variants. The study included 48 patients undergoing inpatient treatment at "Psychiatric Clinical Hospital No. 1" in Moscow, comprising 23 females and 25 males. Inclusion criteria: - Patients aged 18 and above. - Diagnosis according to ICD-10: F20.0, F20.2, F20.8, F21.8, F25.1, F25.2. - Voluntary informed consent from patients. Exclusion criteria included: - The presence of concurrent somatic or neurological pathology, neuroinfections, epilepsy, organic central nervous system damage of any etiology, and regular use of medication. - Substance abuse and alcohol dependence. - Women who were pregnant or breastfeeding. Clinical and psychopathological assessment was complemented by psychometric evaluation using the PANSS scale at the beginning and end of treatment. The duration of observation during therapy was 4-6 weeks. Total DNA extraction was performed using QIAamp DNA. Blood samples were processed on Illumina HiScan and genotyped for 652,297 markers on the Infinium Global Chips Screening Array-24v2.0 using the IMPUTE2 program with parameters Ne=20,000 and k=90. Additional filtration was performed based on INFO>0.5 and genotype probability>0.5. Quality control of the obtained DNA was conducted using agarose gel electrophoresis, with each tested sample having a volume of 100 µL. Results. It was observed that several SNPs exhibited gender dependence. We identified groups of single nucleotide polymorphisms with a membership of 80% or more in either the female or male gender. These SNPs included rs2661319, rs2842030, rs4606, rs11868035, rs518147, rs5993883, and rs6269.Another noteworthy finding was the limited combination of SNPs sufficient to manifest clinical symptoms leading to hospitalization. Among all 48 patients, each of whom was analyzed for deviations in 73 SNPs, it was discovered that the combination of involved SNPs in the manifestation of pronounced clinical symptoms of schizophrenia was 19±3 out of 73 possible. In study, the frequency of occurrence of single nucleotide polymorphisms also varied. The most frequently observed SNPs were rs4849127 (in 90% of cases), rs1150226 (86%), rs1414334 (75%), rs10170310 (73%), rs2857657, and rs4436578 (71%). Conclusion. Thus, the results of this study provide additional evidence that these genes may be associated with the development of schizophrenia spectrum disorders. However, it's impossible cannot rule out the hypothesis that these polymorphisms may be in linkage disequilibrium with other functionally significant polymorphisms that may actually be involved in schizophrenia spectrum disorders. It has been shown that missense SNPs by themselves are likely not causative of the disease but are in strong linkage disequilibrium with non-functional SNPs that may indeed contribute to disease predisposition.

Keywords: gene polymorphisms, genotyping, single nucleotide polymorphisms, schizophrenia.

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97 South African Breast Cancer Mutation Spectrum: Pitfalls to Copy Number Variation Detection Using Internationally Designed Multiplex Ligation-Dependent Probe Amplification and Next Generation Sequencing Panels

Authors: Jaco Oosthuizen, Nerina C. Van Der Merwe

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The National Health Laboratory Services in Bloemfontien has been the diagnostic testing facility for 1830 patients for familial breast cancer since 1997. From the cohort, 540 were comprehensively screened using High-Resolution Melting Analysis or Next Generation Sequencing for the presence of point mutations and/or indels. Approximately 90% of these patients stil remain undiagnosed as they are BRCA1/2 negative. Multiplex ligation-dependent probe amplification was initially added to screen for copy number variation detection, but with the introduction of next generation sequencing in 2017, was substituted and is currently used as a confirmation assay. The aim was to investigate the viability of utilizing internationally designed copy number variation detection assays based on mostly European/Caucasian genomic data for use within a South African context. The multiplex ligation-dependent probe amplification technique is based on the hybridization and subsequent ligation of multiple probes to a targeted exon. The ligated probes are amplified using conventional polymerase chain reaction, followed by fragment analysis by means of capillary electrophoresis. The experimental design of the assay was performed according to the guidelines of MRC-Holland. For BRCA1 (P002-D1) and BRCA2 (P045-B3), both multiplex assays were validated, and results were confirmed using a secondary probe set for each gene. The next generation sequencing technique is based on target amplification via multiplex polymerase chain reaction, where after the amplicons are sequenced parallel on a semiconductor chip. Amplified read counts are visualized as relative copy numbers to determine the median of the absolute values of all pairwise differences. Various experimental parameters such as DNA quality, quantity, and signal intensity or read depth were verified using positive and negative patients previously tested internationally. DNA quality and quantity proved to be the critical factors during the verification of both assays. The quantity influenced the relative copy number frequency directly whereas the quality of the DNA and its salt concentration influenced denaturation consistency in both assays. Multiplex ligation-dependent probe amplification produced false positives due to ligation failure when ligation was inhibited due to a variant present within the ligation site. Next generation sequencing produced false positives due to read dropout when primer sequences did not meet optimal multiplex binding kinetics due to population variants in the primer binding site. The analytical sensitivity and specificity for the South African population have been proven. Verification resulted in repeatable reactions with regards to the detection of relative copy number differences. Both multiplex ligation-dependent probe amplification and next generation sequencing multiplex panels need to be optimized to accommodate South African polymorphisms present within the genetically diverse ethnic groups to reduce the false copy number variation positive rate and increase performance efficiency.

Keywords: familial breast cancer, multiplex ligation-dependent probe amplification, next generation sequencing, South Africa

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96 Economic Impacts of Sanctuary and Immigration and Customs Enforcement Policies Inclusive and Exclusive Institutions

Authors: Alexander David Natanson

Abstract:

This paper focuses on the effect of Sanctuary and Immigration and Customs Enforcement (ICE) policies on local economies. "Sanctuary cities" refers to municipal jurisdictions that limit their cooperation with the federal government's efforts to enforce immigration. Using county-level data from the American Community Survey and ICE data on economic indicators from 2006 to 2018, this study isolates the effects of local immigration policies on U.S. counties. The investigation is accomplished by simultaneously studying the policies' effects in counties where immigrants' families are persecuted via collaboration with Immigration and Customs Enforcement (ICE), in contrast to counties that provide protections. The analysis includes a difference-in-difference & two-way fixed effect model. Results are robust to nearest-neighbor matching, after the random assignment of treatment, after running estimations using different cutoffs for immigration policies, and with a regression discontinuity model comparing bordering counties with opposite policies. Results are also robust after restricting the data to a single-year policy adoption, using the Sun and Abraham estimator, and with event-study estimation to deal with the staggered treatment issue. In addition, the study reverses the estimation to understand what drives the decision to choose policies to detect the presence of reverse causality biases in the estimated policy impact on economic factors. The evidence demonstrates that providing protections to undocumented immigrants increases economic activity. The estimates show gains in per capita income ranging from 3.1 to 7.2, median wages between 1.7 to 2.6, and GDP between 2.4 to 4.1 percent. Regarding labor, sanctuary counties saw increases in total employment between 2.3 to 4 percent, and the unemployment rate declined from 12 to 17 percent. The data further shows that ICE policies have no statistically significant effects on income, median wages, or GDP but adverse effects on total employment, with declines from 1 to 2 percent, mostly in rural counties, and an increase in unemployment of around 7 percent in urban counties. In addition, results show a decline in the foreign-born population in ICE counties but no changes in sanctuary counties. The study also finds similar results for sanctuary counties when separating the data between urban, rural, educational attainment, gender, ethnic groups, economic quintiles, and the number of business establishments. The takeaway from this study is that institutional inclusion creates the dynamic nature of an economy, as inclusion allows for economic expansion due to the extension of fundamental freedoms to newcomers. Inclusive policies show positive effects on economic outcomes with no evident increase in population. To make sense of these results, the hypothesis and theoretical model propose that inclusive immigration policies play an essential role in conditioning the effect of immigration by decreasing uncertainties and constraints for immigrants' interaction in their communities, decreasing the cost from fear of deportation or the constant fear of criminalization and optimize their human capital.

Keywords: inclusive and exclusive institutions, post matching, fixed effect, time trend, regression discontinuity, difference-in-difference, randomization inference and sun, Abraham estimator

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95 Impact of Water Interventions under WASH Program in the South-west Coastal Region of Bangladesh

Authors: S. M. Ashikur Elahee, Md. Zahidur Rahman, Md. Shofiqur Rahman

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This study evaluated the impact of different water interventions under WASH program on access of household's to safe drinking water. Following survey method, the study was carried out in two Upazila of South-west coastal region of Bangladesh namely Koyra from Khulna and Shymnagar from Satkhira district. Being an explanatory study, a total of 200 household's selected applying random sampling technique were interviewed using a structured interview schedule. The predicted probability suggests that around 62 percent household's are out of year-round access to safe drinking water whereby, only 25 percent household's have access at SPHERE standard (913 Liters/per person/per year). Besides, majority (78 percent) of the household's have not accessed at both indicators simultaneously. The distance from household residence to the water source varies from 0 to 25 kilometer with an average distance of 2.03 kilometers. The study also reveals that the increase in monthly income around BDT 1,000 leads to additional 11 liters (coefficient 0.01 at p < 0.1) consumption of safe drinking water for a person/year. As expected, lining up time has significant negative relationship with dependent variables i.e., for higher lining up time, the probability of getting access for both SPHERE standard and year round access variables becomes lower. According to ordinary least square (OLS) regression results, water consumption decreases at 93 liters for per person/year of a household if one member is added to that household. Regarding water consumption intensity, ordered logistic regression (OLR) model shows that one-minute increase of lining up time for water collection tends to reduce water consumption intensity. On the other hand, as per OLS regression results, for one-minute increase of lining up time, the water consumption decreases by around 8 liters. Considering access to Deep Tube Well (DTW) as a reference dummy, in OLR, the household under Pond Sand Filter (PSF), Shallow Tube Well (STW), Reverse Osmosis (RO) and Rainwater Harvester System (RWHS) are respectively 37 percent, 29 percent, 61 percent and 27 percent less likely to ensure year round access of water consumption. In line of health impact, different type of water born diseases like diarrhea, cholera, and typhoid are common among the coastal community caused by microbial impurities i.e., Bacteria, Protozoa. High turbidity and TDS in pond water caused by reduction of water depth, presence of suspended particle and inorganic salt stimulate the growth of bacteria, protozoa, and algae causes affecting health hazard. Meanwhile, excessive growth of Algae in pond water caused by excessive nitrate in drinking water adversely effects on child health. In lieu of ensuring access at SPHERE standard, we need to increase the number of water interventions at reasonable distance, preferably a half kilometer away from the dwelling place, ensuring community peoples involved with its installation process where collectively owned water intervention is found more effective than privately owned. In addition, a demand-responsive approach to supply of piped water should be adopted to allow consumer demand to guide investment in domestic water supply in future.

Keywords: access, impact, safe drinking water, Sphere standard, water interventions

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94 The Regulation of the Cancer Epigenetic Landscape Lies in the Realm of the Long Non-coding RNAs

Authors: Ricardo Alberto Chiong Zevallos, Eduardo Moraes Rego Reis

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Pancreatic adenocarcinoma (PDAC) patients have a less than 10% 5-year survival rate. PDAC has no defined diagnostic and prognostic biomarkers. Gemcitabine is the first-line drug in PDAC and several other cancers. Long non-coding RNAs (lncRNAs) contribute to the tumorigenesis and are potential biomarkers for PDAC. Although lncRNAs aren’t translated into proteins, they have important functions. LncRNAs can decoy or recruit proteins from the epigenetic machinery, act as microRNA sponges, participate in protein translocation through different cellular compartments, and even promote chemoresistance. The chromatin remodeling enzyme EZH2 is a histone methyltransferase that catalyzes the methylation of histone 3 at lysine 27, silencing local expression. EZH2 is ambivalent, it can also activate gene expression independently of its histone methyltransferase activity. EZH2 is overexpressed in several cancers and interacts with lncRNAs, being recruited to a specific locus. EZH2 can be recruited to activate an oncogene or silence a tumor suppressor. The lncRNAs misregulation in cancer can result in the differential recruitment of EZH2 and in a distinct epigenetic landscape, promoting chemoresistance. The relevance of the EZH2-lncRNAs interaction to chemoresistant PDAC was assessed by Real Time quantitative PCR (RT-qPCR) and RNA Immunoprecipitation (RIP) experiments with naïve and gemcitabine-resistant PDAC cells. The expression of several lncRNAs and EZH2 gene targets was evaluated contrasting naïve and resistant cells. Selection of candidate genes was made by bioinformatic analysis and literature curation. Indeed, the resistant cell line showed higher expression of chemoresistant-associated lncRNAs and protein coding genes. RIP detected lncRNAs interacting with EZH2 with varying intensity levels in the cell lines. During RIP, the nuclear fraction of the cells was incubated with an antibody for EZH2 and with magnetic beads. The RNA precipitated with the beads-antibody-EZH2 complex was isolated and reverse transcribed. The presence of candidate lncRNAs was detected by RT-qPCR, and the enrichment was calculated relative to INPUT (total lysate control sample collected before RIP). The enrichment levels varied across the several lncRNAs and cell lines. The EZH2-lncRNA interaction might be responsible for the regulation of chemoresistance-associated genes in multiple cancers. The relevance of the lncRNA-EZH2 interaction to PDAC was assessed by siRNA knockdown of a lncRNA, followed by the analysis of the EZH2 target expression by RT-qPCR. The chromatin immunoprecipitation (ChIP) of EZH2 and H3K27me3 followed by RT-qPCR with primers for EZH2 targets also assess the specificity of the EZH2 recruitment by the lncRNA. This is the first report of the interaction of EZH2 and lncRNAs HOTTIP and PVT1 in chemoresistant PDAC. HOTTIP and PVT1 were described as promoting chemoresistance in several cancers, but the role of EZH2 is not clarified. For the first time, the lncRNA LINC01133 was detected in a chemoresistant cancer. The interaction of EZH2 with LINC02577, LINC00920, LINC00941, and LINC01559 have never been reported in any context. The novel lncRNAs-EZH2 interactions regulate chemoresistant-associated genes in PDAC and might be relevant to other cancers. Therapies targeting EZH2 alone weren’t successful, and a combinatorial approach also targeting the lncRNAs interacting with it might be key to overcome chemoresistance in several cancers.

Keywords: epigenetics, chemoresistance, long non-coding RNAs, pancreatic cancer, histone modification

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93 The in Vitro and in Vivo Antifungal Activity of Terminalia Mantaly on Aspergillus Species Using Drosophila melanogaster (UAS-Diptericin) As a Model

Authors: Ponchang Apollos Wuyep, Alice Njolke Mafe, Longchi Satkat Zacheaus, Dogun Ojochogu, Dabot Ayuba Yakubu

Abstract:

Fungi causes huge losses when infections occur both in plants and animals. Synthetic Antifungal drugs are mostly very expensive and highly cytotoxic when taken. This study was aimed at determining the in vitro and in vivo antifungal activities of the leaves and stem extracts of Terminalia mantaly (Umbrella tree)H. Perrier on Aspergillus species in a bid to identify potential sources of cheap starting materials for the synthesis of new drugs to address the growing antimicrobial resistance. T. mantaly leave and stem powdered plant was extracted by fractionation using the method of solvent partition co-efficient in their graded form in the order n-hexane, Ethyl acetate, methanol and distilled water and phytochemical screening of each fraction revealed the presence of alkaloids, saponins, Tannins, flavonoids, carbohydrates, steroids, anthraquinones, cardiac glycosides and terpenoids in varying degrees. The Agar well diffusion technique was used to screen for antifungal activity of the fractions on clinical isolates of Aspergillus species (Aspergillus flavus and Aspergillus fumigatus). Minimum inhibitory concentration (MIC50) of the most active extracts was determined by the broth dilution method. The fractions test indicated a high antifungal activity with zones of inhibition ranging from 6 to 26 mm and 8 to 30mm (leave fractions) and 10mm to 34mm and 14mm to36mm (stem fractions) on A. flavus and A. fumigatus respectively. All the fractions indicated antifungal activity in a dose response relationship at concentrations of 62.5mg/ml, 125mg/ml, 250mg/ml and 500mg/ml. Better antifungal efficacy was shown by the Ethyl acetate, Hexane and Methanol fractions in the in vitro as the most potent fraction with MIC ranging from 62.5 to 125mg/ml. There was no statistically significant difference (P>0.05) in the potency of the Eight fractions from leave and stem (Hexane, Ethyl acetate, methanol and distilled water, antifungal (fluconazole), which served as positive control and 10% DMSO(Dimethyl Sulfoxide)which served as negative control. In the in vivo investigations, the ingestion technique was used for the infectious studies Female Drosophilla melanogaster(UAS-Diptericin)normal flies(positive control),infected and not treated flies (negative control) and infected flies with A. fumigatus and placed on normal diet, diet containing fractions(MSM and HSM each at concentrations of 10mg/ml 20mg/ml, 30mg/ml, 40mg/ml, 50mg/ml, 60mg/ml, 70mg/ml, 80mg/ml, 90mg/ml and 100mg/ml), diet containing control drugs(fluconazole as positive control)and infected flies on normal diet(negative control), the flies were observed for fifteen(15) days. Then the total mortality of flies was recorded each day. The results of the study reveals that the flies were susceptible to infection with A. fumigatus and responded to treatment with more effectiveness at 50mg/ml, 60mg/ml and 70mg/ml for both the Methanol and Hexane stem fractions. Therefore, the Methanol and Hexane stem fractions of T. mantaly contain therapeutically useful compounds, justifying the traditional use of this plant for the treatment of fungal infections.

Keywords: Terminalia mantaly, Aspergillus fumigatus, cytotoxic, Drosophila melanogaster, antifungal

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92 Stent Surface Functionalisation via Plasma Treatment to Promote Fast Endothelialisation

Authors: Irene Carmagnola, Valeria Chiono, Sandra Pacharra, Jochen Salber, Sean McMahon, Chris Lovell, Pooja Basnett, Barbara Lukasiewicz, Ipsita Roy, Xiang Zhang, Gianluca Ciardelli

Abstract:

Thrombosis and restenosis after stenting procedure can be prevented by promoting fast stent wall endothelialisation. It is well known that surface functionalisation with antifouling molecules combining with extracellular matrix proteins is a promising strategy to design biomimetic surfaces able to promote fast endothelialization. In particular, REDV has gained much attention for the ability to enhance rapid endothelialization due to its specific affinity with endothelial cells (ECs). In this work, a two-step plasma treatment was performed to polymerize a thin layer of acrylic acid, used to subsequently graft PEGylated-REDV and polyethylene glycol (PEG) at different molar ratio with the aim to selectively promote endothelial cell adhesion avoiding platelet activation. PEGylate-REDV was provided by Biomatik and it is formed by 6 PEG monomer repetitions (Chempep Inc.), with an NH2 terminal group. PEG polymers were purchased from Chempep Inc. with two different chain lengths: m-PEG6-NH2 (295.4 Da) with 6 monomer repetitions and m-PEG12-NH2 (559.7 Da) with 12 monomer repetitions. Plasma activation was obtained by operating at 50W power, 5 min of treatment and at an Ar flow rate of 20 sccm. Pure acrylic acid (99%, AAc) vapors were diluted in Ar (flow = 20 sccm) and polymerized by a pulsed plasma discharge applying a discharge RF power of 200 W, a duty cycle of 10% (on time = 10 ms, off time = 90 ms) for 10 min. After plasma treatment, samples were dipped into an 1-(3-dimethylaminopropyl)-3- ethylcarbodiimide (EDC)/N-hydroxysuccinimide (NHS) solution (ratio 4:1, pH 5.5) for 1 h at 4°C and subsequently dipped in PEGylate-REDV and PEGylate-REDV:PEG solutions at different molar ratio (100 μg/mL in PBS) for 20 h at room temperature. Surface modification was characterized through physico-chemical analyses and in vitro cell tests. PEGylated-REDV peptide and PEG were successfully bound to the carboxylic groups that are formed on the polymer surface after plasma reaction. FTIR-ATR spectroscopy, X -ray Photoelectron Spectroscopy (XPS) and contact angle measurement gave a clear indication of the presence of the grafted molecules. The use of PEG as a spacer allowed for an increase in wettability of the surface, and the effect was more evident by increasing the amount of PEG. Endothelial cells adhered and spread well on the surfaces functionalized with the REDV sequence. In conclusion, a selective coating able to promote a new endothelial cell layer on polymeric stent surface was developed. In particular, a thin AAc film was polymerised on the polymeric surface in order to expose –COOH groups, and PEGylate-REDV and PEG were successful grafted on the polymeric substrates. The REDV peptide demonstrated to encourage cell adhesion with a consequent, expected improvement of the hemocompatibility of these polymeric surfaces in vivo. Acknowledgements— This work was funded by the European Commission 7th Framework Programme under grant agreement number 604251- ReBioStent (Reinforced Bioresorbable Biomaterials for Therapeutic Drug Eluting Stents). The authors thank all the ReBioStent partners for their support in this work.

Keywords: endothelialisation, plasma treatment, stent, surface functionalisation

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91 Awareness Creation of Benefits of Antitrypsin-Free Nutraceutical Biopowder for Increasing Human Serum Albumin Synthesis as Possible Adjunct for Management of MDRTB or MDRTB-HIV Patients

Authors: Vincent Oghenekevbe Olughor, Olusoji Mayowa Ige

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Except for a preexisting liver disease and malnutrition, there are no predilections for low serum albumin (SA) levels in humans. At normal reference levels (4.0-6.0g/dl) SA is a universal marker for mortality and morbidity risks assessments where depletion by 1.0g/dl increases mortality risk by 137% and morbidity by 89%.It has 40 known functions contributing significantly to the sustenance of human life. A depletion in SA to <2.2g/dl, in most clinical settings worldwide, leads to loss of oncotic pressure of blood causing clinical manifestations of bipedal Oedema, in which the patients remain conscious. SA also contributes significantly to buffering of blood to a life-sustaining pH of 7.35-7.45. A drop in blood pH to <6.9 will lead to instant coma and death, which can occur after SA continues to deplete after manifestations of bipedal Oedema. In an intervention study conducted in 2014 following the discovery that “SA is depleted during malaria fever”, a Nutraceutical formulated for use as treatment adjunct to prevent SA depletions during malaria to <2.4g/dl after Efficacy testing was found to be satisfactory. There are five known types of Malaria caused by Apicomplexan parasites, Plasmodium: the most lethal being that caused by Plasmodium falciparum causing malignant tertian malaria, in which the fever was occurring every 48 hours coincides with the dumping of malaria-toxins (Hemozoin) into blood, causing contamination: blood must remain sterile. Other Apicomplexan parasites, Toxoplasma and Cryptosporidium, are opportunistic infections of HIV. Separate studies showed SA depletions in MDRTB (multidrug resistant TB), and MDRTB-HIV patients by the same mechanism discovered with malaria and such depletions will be further complicated whenever Apicomplexan parasitic infections co-exist. Both Apicomplexan parasites and the TB parasite belong to the Obligate-group of Parasites, which are parasites that replicate only inside its host; and most of them have capacities to over-consume host nutrients during parasitaemia. In MDRTB patients the body attempts repeatedly to prevent depletions in SA to critical levels in the presence of adequate nutrients and only for a while in MDRTB-HIV patients. These groups of patients will, therefore, benefit from the already tested Nutraceutical in malaria patients. The Nutraceutical bio-Powder was formulated (to BP 1988 specification) from twelve nature-based food-grade nutrients containing all dedicated nutrients for ensuring improved synthesis of Albumin by the liver. The Nutraceutical was administered daily for 38±2days in 23 children, in a prospective phase-2 clinical trial, and its impact on body weight and core blood parameters were documented at the start and end of efficacy testing period. Sixteen children who did not experience malaria-induced depletions of SA had significant SA increase; seven children who experienced malaria-induced depletions of SA had insignificant SA decrease. The Packed Cell Volume Percentage (PCV %), a measure of the Oxygen carrying capacity of blood and the amount of nutrients the body can absorb, increased in both groups. The total serum proteins (SA+ Globulins) increased or decreased within the continuum of normal. In conclusion, MDRTB and MDRTB-HIV patients will benefit from a variant of this Nutraceutical when used as treatment adjunct.

Keywords: antitrypsin-free Nutraceutical, apicomplexan parasites, no predilections for low serum albumin, toxoplasmosis

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90 On the Utility of Bidirectional Transformers in Gene Expression-Based Classification

Authors: Babak Forouraghi

Abstract:

A genetic circuit is a collection of interacting genes and proteins that enable individual cells to implement and perform vital biological functions such as cell division, growth, death, and signaling. In cell engineering, synthetic gene circuits are engineered networks of genes specifically designed to implement functionalities that are not evolved by nature. These engineered networks enable scientists to tackle complex problems such as engineering cells to produce therapeutics within the patient's body, altering T cells to target cancer-related antigens for treatment, improving antibody production using engineered cells, tissue engineering, and production of genetically modified plants and livestock. Construction of computational models to realize genetic circuits is an especially challenging task since it requires the discovery of the flow of genetic information in complex biological systems. Building synthetic biological models is also a time-consuming process with relatively low prediction accuracy for highly complex genetic circuits. The primary goal of this study was to investigate the utility of a pre-trained bidirectional encoder transformer that can accurately predict gene expressions in genetic circuit designs. The main reason behind using transformers is their innate ability (attention mechanism) to take account of the semantic context present in long DNA chains that are heavily dependent on the spatial representation of their constituent genes. Previous approaches to gene circuit design, such as CNN and RNN architectures, are unable to capture semantic dependencies in long contexts, as required in most real-world applications of synthetic biology. For instance, RNN models (LSTM, GRU), although able to learn long-term dependencies, greatly suffer from vanishing gradient and low-efficiency problem when they sequentially process past states and compresses contextual information into a bottleneck with long input sequences. In other words, these architectures are not equipped with the necessary attention mechanisms to follow a long chain of genes with thousands of tokens. To address the above-mentioned limitations, a transformer model was built in this work as a variation to the existing DNA Bidirectional Encoder Representations from Transformers (DNABERT) model. It is shown that the proposed transformer is capable of capturing contextual information from long input sequences with an attention mechanism. In previous works on genetic circuit design, the traditional approaches to classification and regression, such as Random Forrest, Support Vector Machine, and Artificial Neural Networks, were able to achieve reasonably high R2 accuracy levels of 0.95 to 0.97. However, the transformer model utilized in this work, with its attention-based mechanism, was able to achieve a perfect accuracy level of 100%. Further, it is demonstrated that the efficiency of the transformer-based gene expression classifier is not dependent on the presence of large amounts of training examples, which may be difficult to compile in many real-world gene circuit designs.

Keywords: machine learning, classification and regression, gene circuit design, bidirectional transformers

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89 Children’s Experience of the Built Environment in the Initial Stages of a Settlement Formation: Case Study of Shahid-Keshvari New Settlement, Isfahan, Iran

Authors: Hassan Sheikh, Mehdi Nilipour, Amiraslan Fila

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Many conventional town planning processes do little to give children and young people a voice on what is important about the urban environment. As a result of paying little attention to the children, their physical, social and mental needs are hardly met in urban environments. Therefore, urban spaces are impotent to attract children, while their recreational space has been confined to home or virtual spaces. Since children are just taking the first steps to learn the world beyond house borders, their living environment will profoundly influence almost all aspects of their lives. This puts a great deal of responsibility on the shoulders of planners, who need to balance a number of different issues in urban design to make places more child-friendly. The main purpose of present research is to analyze and plan a child-friendly environment in an on-going urban settlement development for the benefit of all residents. Assessing children’s needs and regard them in development strategies and policies will help to “plan for children”. Following this purpose, based on child-friendly environment studies, indicators of child-friendly environments were collected. Then three distinct characteristics of case study, which are being under-construction, lack of social ties between dwellers and high-rise building, determined seven indicators included basic services, Urban and environmental qualities, Family, kin, peers and community, Sense of belonging and continuity, participation, Safety, security and freedom of movement and human scale. With the survey, Informal observation and participation in small communities, essential data has been collected and analyzed by SPSS software. The field study is Shahid-Keshvari town in Isfahan, Iran. Eighty-six middle childhood, children (ages 8-13) participated. The results show Children's satisfaction is correlated with basic services and the quality of the environment, social environment and the safety and security. The considerable number of children and youth (55%) like to live somewhere other than the town. Satisfaction and sense of belonging and continuity have a strong inverse correlation with age. In other words, as age increases, satisfaction and consequently a sense of belonging will be reduced; thus children and youth consider their future somewhere out of the town. The main reason for dissatisfaction was the basic services and social environment. More than half of children (55%) expressed their wish to develop basic services in terms of availability, hierarchy, and quality. Among all recreational places, children showed more interest to the parks. About three-quarters (76%) considered building a park as a crucial item for residents. The significant number of children (54%) want to have a relationship with more friends. This could be due to the serious shortage of the leisure spaces such as parks or playgrounds. Also, the space around the house or space between the apartments has not been designed for play or children’s activities. Moreover, the presence of strangers and construction workers have a negative impact on children's sense of peace and security; 60% of children are afraid of theft and 36% of children found strangers as a menace. The analysis of children’s issues and suggestions provides an insight to plan and design of child-friendly environment in new towns.

Keywords: child-friendly city (CFC), child-friendly environment, child participation, under-construction environment, Isfahan Shahid-Keshvari Town

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88 Effect of Velocity-Slip in Nanoscale Electroosmotic Flows: Molecular and Continuum Transport Perspectives

Authors: Alper T. Celebi, Ali Beskok

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Electroosmotic (EO) slip flows in nanochannels are investigated using non-equilibrium molecular dynamics (MD) simulations, and the results are compared with analytical solution of Poisson-Boltzmann and Stokes (PB-S) equations with slip contribution. The ultimate objective of this study is to show that well-known continuum flow model can accurately predict the EO velocity profiles in nanochannels using the slip lengths and apparent viscosities obtained from force-driven flow simulations performed at various liquid-wall interaction strengths. EO flow of aqueous NaCl solution in silicon nanochannels are simulated under realistic electrochemical conditions within the validity region of Poisson-Boltzmann theory. A physical surface charge density is determined for nanochannels based on dissociations of silanol functional groups on channel surfaces at known salt concentration, temperature and local pH. First, we present results of density profiles and ion distributions by equilibrium MD simulations, ensuring that the desired thermodynamic state and ionic conditions are satisfied. Next, force-driven nanochannel flow simulations are performed to predict the apparent viscosity of ionic solution between charged surfaces and slip lengths. Parabolic velocity profiles obtained from force-driven flow simulations are fitted to a second-order polynomial equation, where viscosity and slip lengths are quantified by comparing the coefficients of the fitted equation with continuum flow model. Presence of charged surface increases the viscosity of ionic solution while the velocity-slip at wall decreases. Afterwards, EO flow simulations are carried out under uniform electric field for different liquid-wall interaction strengths. Velocity profiles present finite slips near walls, followed with a conventional viscous flow profile in the electrical double layer that reaches a bulk flow region in the center of the channel. The EO flow enhances with increased slip at the walls, which depends on wall-liquid interaction strength and the surface charge. MD velocity profiles are compared with the predictions from analytical solutions of the slip modified PB-S equation, where the slip length and apparent viscosity values are obtained from force-driven flow simulations in charged silicon nano-channels. Our MD results show good agreements with the analytical solutions at various slip conditions, verifying the validity of PB-S equation in nanochannels as small as 3.5 nm. In addition, the continuum model normalizes slip length with the Debye length instead of the channel height, which implies that enhancement in EO flows is independent of the channel height. Further MD simulations performed at different channel heights also shows that the flow enhancement due to slip is independent of the channel height. This is important because slip enhanced EO flow is observable even in micro-channels experiments by using a hydrophobic channel with large slip and high conductivity solutions with small Debye length. The present study provides an advanced understanding of EO flows in nanochannels. Correct characterization of nanoscale EO slip flow is crucial to discover the extent of well-known continuum models, which is required for various applications spanning from ion separation to drug delivery and bio-fluidic analysis.

Keywords: electroosmotic flow, molecular dynamics, slip length, velocity-slip

Procedia PDF Downloads 134
87 Guard@Lis: Birdwatching Augmented Reality Mobile Application

Authors: Jose A. C. Venancio, Alexandrino J. M. Goncalves, Anabela Marto, Nuno C. S. Rodrigues, Rita M. T. Ascenso

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Nowadays, it is common to find people who are concerned about getting away from the everyday life routine, looking forward to outcome well-being and pleasant emotions. Trying to disconnect themselves from the usual places of work and residence, they pursue different places, such as tourist destinations, aiming to have unexpected experiences. In order to make this exploration process easier, cities and tourism agencies seek new opportunities and solutions, creating routes with diverse cultural landmarks, including natural landscapes and historic buildings. These offers frequently aspire to the preservation of the local patrimony. In nature and wildlife, birdwatching is an activity that has been increasing, both in cities and in the countryside. This activity seeks to find, observe and identify the diversity of birds that live permanently or temporarily in these places, and it is usually supported by birdwatching guides. Leiria (Portugal) is a well-known city, presenting several historical and natural landmarks, like the Lis river and the castle where King D. Dinis lived in the 13th century. Along the Lis River, a conservation process was carried out and a pedestrian route was created (Polis project). This is considered an excellent spot for birdwatching, especially for the gray heron (Ardea cinerea) and for the kingfisher (Alcedo atthis). There is also a route through the city, from the riverside to the castle, which encloses a characterized variety of species, such as the barn swallow (Hirundo rustica), known for passing through different seasons of the year. Birdwatching is sometimes a difficult task since it is not always possible to see all bird species that inhabit a given place. For this reason, a need to create a technological solution was found to ease this activity. This project aims to encourage people to learn about the various species of birds that live along the Lis River and to promote the preservation of nature in a conscious way. This work is being conducted in collaboration with Leiria Municipal Council and with the Environmental Interpretation Centre. It intends to show the majesty of the Lis River, a place visited daily by several people, such as children and families, who use it for didactic and recreational activities. We are developing a mobile multi-platform application (Guard@Lis) that allows bird species to be observed along a given route, using representative digital 3D models through the integration of augmented reality technologies. Guard@Lis displays a route with points of interest for birdwatching and a list of species for each point of interest, along with scientific information, images and sounds for every species. For some birds, to ensure their observation, the user can watch them in loco, in their real and natural environment, with their mobile device by means of augmented reality, giving the sensation of presence of these birds, even if they cannot be seen in that place at that moment. The augmented reality feature is being developed with Vuforia SDK, using a hybrid approach to recognition and tracking processes, combining marks and geolocation techniques. This application proposes routes and notifies users with alerts for the possibility of viewing models of augmented reality birds. The final Guard@Lis prototype will be tested by volunteers in-situ.

Keywords: augmented reality, birdwatching route, mobile application, nature tourism, watch birds using augmented reality

Procedia PDF Downloads 150
86 Becoming a Good-Enough White Therapist: Experiences of International Students in Psychology Doctoral Programs

Authors: Mary T. McKinley

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As socio-economic globalization impacts education and turns knowledge into a commodity, institutions of higher education are becoming more intentional about infusing a global and intercultural perspective into education via the recruitment of international students. Coming from dissimilar cultures, many of these students are evaluated and held accountable to Euro-American values of independence, self-reliance, and autonomy. Not surprisingly, these students often experience culture shock with deleterious effects on their mental health and academic functioning. Thus, it is critical to understand the experiences of international students with the hope that such knowledge will keep the field of psychology from promulgating Eurocentric ideals and values and prevent the training of these students as good-enough White therapists. Using a critical narrative inquiry framework, this study elicits stories about the challenges encountered by international students as they navigate their clinical training in the presence of acculturative stress and potentially different worldviews. With its emphasis on story-telling as meaning making, narrative research design is hinged on the assumption that people are interpretive beings who make meaning of themselves and their world through the language of stories. Also, dominant socially-constructed narratives play a central role in creating and maintaining hegemonic structures that privilege certain individuals and ideologies at the expense of others. On this premise, narrative inquiry begins with an exploration of the experiences of participants in their lived stories. Bounded narrative segments were read, interpreted, and analyzed using a critical events approach. Throughout the process, issues of reliability and researcher bias were addressed by keeping a reflective analytic memo, as well as triangulating the data using peer-reviewers and check-ins with participants. The findings situate culture at the epicenter of international students’ acculturation challenges as well as their resiliency in psychology doctoral programs. It was not uncommon for these international students to experience ethical dilemmas inherent in learning content that conflicted with their cultural beliefs and values. Issues of cultural incongruence appear to be further exacerbated by visible markers for differences like speech accent and clothing attire. These stories also link the acculturative stress reported by international students to the experiences of perceived racial discrimination and lack of support from the faculty, administration, peers, and the society at large. Beyond the impact on the international students themselves, there are implications for internationalization in psychology with the goal of equipping doctoral programs to be better prepared to meet the needs of their international students. More than ever before, programs need to liaise with international students’ services and work in tandem to meet the unique needs of this population of students. Also, there exists a need for multiculturally competent supervisors working with international students with varying degrees of acculturation. In addition to making social justice and advocacy salient in students’ multicultural training, it may be helpful for psychology doctoral programs to be more intentional about infusing cross-cultural theories, indigenous psychotherapies, and/or when practical, the possibility for geographically cross-cultural practicum experiences in the home countries of international students while taking into consideration the ethical issues for virtual supervision.

Keywords: decolonizing pedagogies, international students, multiculturalism, psychology doctoral programs

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85 Central Nervous System Lesion Differentiation in the Emergency Radiology Department

Authors: Angelis P. Barlampas

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An 89 years old woman came to the emergency department complaining of long-lasting headaches and nausea. A CT examination was performed, and a homogeneous midline anterior cranial fossa lesion was revealed, which was situated near the base and measured 2,4 cm in diameter. The patient was allergic, and an i.v.c injection could not be done on the spot, and neither could an MRI exam because of metallic implants. How could someone narrow down the differential diagnosis? The interhemispheric meningioma is usually a silent midline lesion with no edema, and most often presents as a homogeneous, solid type, isodense, or slightly hyperdense mass ( usually the smallest lesions as this one ). Of them, 20-30% have some calcifications. Hyperostosis is typical for meningiomas that abut the base of the skull but is absent in the current case, presumably of a more cephalad location that is borderline away from the bone. Because further investigation could not be done, as the patient was allergic to the contrast media, some other differential options should be considered. Regarding the site of the lesion, the most common other entities to keep in mind are the following: Metastasis, tumor of skull base, abscess, primary brain tumors, meningioma, giant aneurysm of the anterior cerebral artery, olfactory neuroblastoma, interhemispheric meningioma, giant aneurysm of the anterior cerebral artery, midline lesion. Appearance will depend on whether the aneurysm is non-thrombosed, or partially, or completely thrombosed. Non-contrast: slightly hyperdense, well-defined round extra-axial mass, may demonstrate a peripheral calcified rim, olfactory neuroblastoma, midline lesion. The mass is of soft tissue attenuation and is relatively homogeneous. Focal calcifications are occasionally present. When an intracranial extension is present, peritumoral cysts between it and the overlying brain are often present. Final diagnosis interhemispheric meningioma (Known from the previous patient’s history). Meningiomas come from the meningocytes or the arachnoid cells of the meninges. They are usually found incidentally, have an indolent course, and their most common location is extra-axial, parasagittal, and supratentorial. Other locations include the sphenoid ridge, olfactory groove, juxtasellar, infratentorial, intraventricular, pineal gland area, and optic nerve meningioma. They are clinically silent entities, except for large ones, which can present with headaches, changes in personality status, paresis, or symptomatology according to their specific site and may cause edema of the surrounding brain tissue. Imaging findings include the presence of calcifications, the CSF cleft sign, hyperostosis of adjacent bone, dural tail, and white matter buckling sign. After i.v.c. injection, they enhance brightly and homogenously, except for large ones, which may exhibit necrotic areas or may be heavily calcified. Malignant or cystic variants demonstrate more heterogeneity and less intense enhancement. Sometimes, it is inevitable that the needed CT protocol cannot be performed, especially in the emergency department. In these cases, the radiologist must focus on the characteristic imaging features of the unenhanced lesion, as well as in previous examinations or a known lesion history, in order to come to the right report conclusion.

Keywords: computed tomography, emergency radiology, metastasis, tumor of skull base, abscess, primary brain tumors, meningioma, giant aneurysm of the anterior cerebral artery, olfactory neuroblastoma, interhemispheric meningioma

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84 Role of Toll Like Receptor-2 in Female Genital Tuberculosis Disease Infection and Its Severity

Authors: Swati Gautam, Salman Akhtar, S. P. Jaiswar, Amita Jain

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Background: FGTB is now a major global health problem mostly in developing countries including India. In humans, Mycobacterium Tuberculosis (M.tb) is a causating agent of infection. High index of suspicion is required for early diagnosis due to asymptomatic presentation of FGTB disease. In macrophages Toll Like Receptor-2 (TLR-2) is one which mediated host’s immune response to M.tb. The expression of TLR-2 on macrophages is important to determine the fate of innate immune responses to M.tb. TLR-2 have two work. First its high expression on macrophages worsen the outer of infection and another side, it maintains M.tb to its dormant stage avoids activation of M.tb from latent phase. Single Nucleotide Polymorphism (SNP) of TLR-2 gene plays an important role in susceptibility to TB among different populations and subsequently, in the development of infertility. Methodology: This Case-Control study was done in the Department of Obs and Gynae and Department of Microbiology at King George’s Medical University, U.P, Lucknow, India. Total 300 subjects (150 Cases and 150 Controls) were enrolled in the study. All subjects were enrolled only after fulfilling the given inclusion and exclusion criteria. Inclusion criteria: Age 20-35 years, menstrual-irregularities, positive on Acid-Fast Bacilli (AFB), TB-PCR, (LJ/MGIT) culture in Endometrial Aspiration (EA). Exclusion criteria: Koch’s active, on ATT, PCOS, and Endometriosis fibroid women, positive on Gonococal and Chlamydia. Blood samples were collected in EDTA tubes from cases and healthy control women (HCW) and genomic DNA extraction was carried out by salting-out method. Genotyping of TLR2 genetic variants (Arg753Gln and Arg677Trp) were performed by using single amplification refractory mutation system (ARMS) PCR technique. PCR products were analyzed by electrophoresis on 1.2% agarose gel and visualized by gel-doc. Statistical analysis of the data was performed using the SPSS 16.3 software and computing odds ratio (OR) with 95% CI. Linkage Disequiliribium (LD) analysis was done by SNP stats online software. Results: In TLR-2 (Arg753Gln) polymorphism significant risk of FGTB observed with GG homozygous mutant genotype (OR=13, CI=0.71-237.7, p=0.05), AG heterozygous mutant genotype (OR=13.7, CI=0.76-248.06, p=0.03) however, G allele (OR=1.09, CI=0.78-1.52, p=0.67) individually was not associated with FGTB. In TLR-2 (Arg677Trp) polymorphism a significant risk of FGTB observed with TT homozygous mutant genotype (OR= 0.020, CI=0.001-0.341, p < 0.001), CT heterozygous mutant genotype (OR=0.53, CI=0.33-0.86, p=0.014) and T allele (OR=0.463, CI=0.32-0.66, p < 0.001). TT mutant genotype was only found in FGTB cases and frequency of CT heterozygous more in control group as compared to FGTB group. So, CT genotype worked as protective mutation for FGTB susceptibility group. In haplotype analysis of TLR-2 genetic variants, four possible combinations, i.e. (G-T, A-C, G-C, and A-T) were obtained. The frequency of haplotype A-C was significantly higher in FGTB cases (0.32). Control group did not show A-C haplotype and only found in FGTB cases. Conclusion: In conclusion, study showed a significant association with both genetic variants of TLR-2 of FGTB disease. Moreover, the presence of specific associated genotype/alleles suggest the possibility of disease severity and clinical approach aimed to prevent extensive damage by disease and also helpful for early detection of disease.

Keywords: ARMS, EDTA, FGTB, TLR

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83 Food Processing Technology and Packaging: A Case Study of Indian Cashew-Nut Industry

Authors: Parashram Jakappa Patil

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India is the global leader in world cashew business and cashew-nut industry is one of the important food processing industries in world. However India is the largest producer, processor, exporter and importer eschew in the world. India is providing cashew to the rest of the world. India is meeting world demand of cashew. India has a tremendous potential of cashew production and export to other countries. Every year India earns more than 2000 cores rupees through cashew trade. Cashew industry is one of the important small scale industries in the country which is playing significant role in rural development. It is generating more than 400000 jobs at remote area and 95% cashew worker are women, it is giving income to poor cashew farmers, majority cashew processing units are small and cottage, it is helping to stop migration from young farmers for employment opportunities, it is motivation rural entrepreneurship development and it is also helping to environment protection etc. Hence India cashew business is very important agribusiness in India which has potential make inclusive development. World Bank and IMF recognized cashew-nut industry is one the important tool for poverty eradication at global level. It shows important of cashew business and its strong existence in India. In spite of such huge potential cashew processing industry is facing different problems such as lack of infrastructure ability, lack of supply of raw cashew, lack of availability of finance, collection of raw cashew, unavailability of warehouse, marketing of cashew kernels, lack of technical knowledge and especially processing technology and packaging of finished products. This industry has great prospects such as scope for more cashew cultivation and cashew production, employment generation, formation of cashew processing units, alcohols production from cashew apple, shield oil production, rural development, poverty elimination, development of social and economic backward class and environment protection etc. This industry has domestic as well as foreign market; India has tremendous potential in this regard. The cashew is a poor men’s crop but rich men’s food. The cashew is a source of income and livelihood for poor farmers. Cashew-nut industry may play very important role in the development of hilly region. The objectives of this paper are to identify problems of cashew processing and use of processing technology, problems of cashew kernel packaging, evolving of cashew processing technology over the year and its impact on final product and impact of good processing by adopting appropriate technology packaging on international trade of cashew-nut. The most important problem of cashew processing industry is that is processing and packaging. Bad processing reduce the quality of cashew kernel at large extent especially broken of cashew kernel which has very less price in market compare to whole cashew kernel and not eligible for export. On the other hand if there is no good packaging of cashew kernel will get moisture which destroy test of it. International trade of cashew-nut is depend of two things one is cashew processing and other is packaging. This study has strong relevance because cashew-nut industry is the labour oriented, where processing technology is not playing important role because 95% processing work is manual. Hence processing work was depending on physical performance of worker which makes presence of large workforce inevitable. There are many cashew processing units closed because they are not getting sufficient work force. However due to advancement in technology slowly this picture is changing and processing work get improve. Therefore it is interesting to explore all the aspects in context of cashew processing and packaging of cashew business.

Keywords: cashew, processing technology, packaging, international trade, change

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82 Differential Expression Profile Analysis of DNA Repair Genes in Mycobacterium Leprae by qPCR

Authors: Mukul Sharma, Madhusmita Das, Sundeep Chaitanya Vedithi

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Leprosy is a chronic human disease caused by Mycobacterium leprae, that cannot be cultured in vitro. Though treatable with multidrug therapy (MDT), recently, bacteria reported resistance to multiple antibiotics. Targeting DNA replication and repair pathways can serve as the foundation of developing new anti-leprosy drugs. Due to the absence of an axenic culture medium for the propagation of M. leprae, studying cellular processes, especially those belonging to DNA repair pathways, is challenging. Genomic understanding of M. Leprae harbors several protein-coding genes with no previously assigned function known as 'hypothetical proteins'. Here, we report identification and expression of known and hypothetical DNA repair genes from a human skin biopsy and mouse footpads that are involved in base excision repair, direct reversal repair, and SOS response. Initially, a bioinformatics approach was employed based on sequence similarity, identification of known protein domains to screen the hypothetical proteins in the genome of M. leprae, that are potentially related to DNA repair mechanisms. Before testing on clinical samples, pure stocks of bacterial reference DNA of M. leprae (NHDP63 strain) was used to construct standard graphs to validate and identify lower detection limit in the qPCR experiments. Primers were designed to amplify the respective transcripts, and PCR products of the predicted size were obtained. Later, excisional skin biopsies of newly diagnosed untreated, treated, and drug resistance leprosy cases from SIHR & LC hospital, Vellore, India were taken for the extraction of RNA. To determine the presence of the predicted transcripts, cDNA was generated from M. leprae mRNA isolated from clinically confirmed leprosy skin biopsy specimen across all the study groups. Melting curve analysis was performed to determine the integrity of the amplification and to rule out primer‑dimer formation. The Ct values obtained from qPCR were fitted to standard curve to determine transcript copy number. Same procedure was applied for M. leprae extracted after processing a footpad of nude mice of drug sensitive and drug resistant strains. 16S rRNA was used as positive control. Of all the 16 genes involved in BER, DR, and SOS, differential expression pattern of the genes was observed in terms of Ct values when compared to human samples; this was because of the different host and its immune response. However, no drastic variation in gene expression levels was observed in human samples except the nth gene. The higher expression of nth gene could be because of the mutations that may be associated with sequence diversity and drug resistance which suggests an important role in the repair mechanism and remains to be explored. In both human and mouse samples, SOS system – lexA and RecA, and BER genes AlkB and Ogt were expressing efficiently to deal with possible DNA damage. Together, the results of the present study suggest that DNA repair genes are constitutively expressed and may provide a reference for molecular diagnosis, therapeutic target selection, determination of treatment and prognostic judgment in M. leprae pathogenesis.

Keywords: DNA repair, human biopsy, hypothetical proteins, mouse footpads, Mycobacterium leprae, qPCR

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81 Converting Urban Organic Waste into Aquaculture Feeds: A Two-Step Bioconversion Approach

Authors: Aditi Chitharanjan Parmar, Marco Gottardo, Giulia Adele Tuci, Francesco Valentino

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The generation of urban organic waste is a significant environmental problem due to the potential release of leachate and/or methane into the environment. This contributes to climate change, discharging a valuable resource that could be used in various ways. This research addresses this issue by proposing a two-step approach by linking biowaste management to aquaculture industry via single cell proteins (SCP) production. A mixture of food waste and municipal sewage sludge (FW-MSS) was firstly subjected to a mesophilic (37°C) anaerobic fermentation to produce a liquid stream rich in short-chain fatty acids (SCFAs), which are important building blocks for the following microbial biomass growth. In the frame of stable fermentation activity (after 1 week of operation), the average value of SCFAs was 21.3  0.4 g COD/L, with a CODSCFA/CODSOL ratio of 0.77 COD/COD. This indicated the successful strategy to accumulate SCFAs from the biowaste mixture by applying short hydraulic retention time (HRT; 4 days) and medium organic loading rate (OLR; 7 – 12 g VS/L d) in the lab-scale (V = 4 L) continuous stirred tank reactor (CSTR). The SCFA-rich effluent was then utilized as feedstock for the growth of a mixed microbial consortium able to store polyhydroxyalkanoates (PHA), a class of biopolymers completely biodegradable in nature and produced as intracellular carbon/energy source. Given the demonstrated properties of the intracellular PHA as antimicrobial and immunomodulatory effect on various fish species, the PHA-producing culture was intended to be utilized as SCP in aquaculture. The growth of PHA-storing biomass was obtained in a 2-L sequencing batch reactor (SBR), fully aerobic and set at 25°C; to stimulate a certain storage response (PHA production) in the cells, the feast-famine conditions were adopted, consisting in an alternation of cycles during which the biomass was exposed to an initial abundance of substrate (feast phase) followed by a starvation period (famine phase). To avoid the proliferation of other bacteria not able to store PHA, the SBR was maintained at low HRT (2 days). Along the stable growth of the mixed microbial consortium (the growth yield was estimated to be 0.47 COD/COD), the feast-famine strategy enhanced the PHA production capacity, leading to a final PHA content in the biomass equal to 16.5 wt%, which is suitable for the use as SCP. In fact, by incorporating the waste-derived PHA-rich biomass into fish feed at 20 wt%, the final feed could contain a PHA content around 3.0 wt%, within the recommended range (0.2–5.0 wt%) for promoting fish health. Proximate analysis of the PHA-rich biomass revealed a good crude proteins level (around 51 wt%) and the presence of all the essential amino acids (EAA), together accounting for 31% of the SCP total amino acid composition. This suggested that the waste-derived SCP was a source of good quality proteins with a good nutritional value. This approach offers a sustainable solution for urban waste management, potentially establishing a sustainable waste-to-value conversion route by connecting waste management to the growing aquaculture and fish feed production sectors.

Keywords: feed supplement, nutritional value, polyhydroxyalkanoates (PHA), single cell protein (SCP), urban organic waste.

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80 Physiological Effects during Aerobatic Flights on Science Astronaut Candidates

Authors: Pedro Llanos, Diego García

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Spaceflight is considered the last frontier in terms of science, technology, and engineering. But it is also the next frontier in terms of human physiology and performance. After more than 200,000 years humans have evolved under earth’s gravity and atmospheric conditions, spaceflight poses environmental stresses for which human physiology is not adapted. Hypoxia, accelerations, and radiation are among such stressors, our research involves suborbital flights aiming to develop effective countermeasures in order to assure sustainable human space presence. The physiologic baseline of spaceflight participants is subject to great variability driven by age, gender, fitness, and metabolic reserve. The objective of the present study is to characterize different physiologic variables in a population of STEM practitioners during an aerobatic flight. Cardiovascular and pulmonary responses were determined in Science Astronaut Candidates (SACs) during unusual attitude aerobatic flight indoctrination. Physiologic data recordings from 20 subjects participating in high-G flight training were analyzed. These recordings were registered by wearable sensor-vest that monitored electrocardiographic tracings (ECGs), signs of dysrhythmias or other electric disturbances during all the flight. The same cardiovascular parameters were also collected approximately 10 min pre-flight, during each high-G/unusual attitude maneuver and 10 min after the flights. The ratio (pre-flight/in-flight/post-flight) of the cardiovascular responses was calculated for comparison of inter-individual differences. The resulting tracings depicting the cardiovascular responses of the subjects were compared against the G-loads (Gs) during the aerobatic flights to analyze cardiovascular variability aspects and fluid/pressure shifts due to the high Gs. In-flight ECG revealed cardiac variability patterns associated with rapid Gs onset in terms of reduced heart rate (HR) and some scattered dysrhythmic patterns (15% premature ventricular contractions-type) that were considered as triggered physiological responses to high-G/unusual attitude training and some were considered as instrument artifact. Variation events were observed in subjects during the +Gz and –Gz maneuvers and these may be due to preload and afterload, sudden shift. Our data reveal that aerobatic flight influenced the breathing rate of the subject, due in part by the various levels of energy expenditure due to the increased use of muscle work during these aerobatic maneuvers. Noteworthy was the high heterogeneity in the different physiological responses among a relatively small group of SACs exposed to similar aerobatic flights with similar Gs exposures. The cardiovascular responses clearly demonstrated that SACs were subjected to significant flight stress. Routine ECG monitoring during high-G/unusual attitude flight training is recommended to capture pathology underlying dangerous dysrhythmias in suborbital flight safety. More research is currently being conducted to further facilitate the development of robust medical screening, medical risk assessment approaches, and suborbital flight training in the context of the evolving commercial human suborbital spaceflight industry. A more mature and integrative medical assessment method is required to understand the physiology state and response variability among highly diverse populations of prospective suborbital flight participants.

Keywords: g force, aerobatic maneuvers, suborbital flight, hypoxia, commercial astronauts

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79 Mesovarial Morphological Changes in Offspring Exposed to Maternal Cold Stress

Authors: Ariunaa.S., Javzandulam E., Chimegsaikhan S., Altantsetseg B., Oyungerel S., Bat-Erdene T., Naranbaatar S., Otgonbayar B., Suvdaa N., Tumenbayar B.

Abstract:

Introduction: Prenatal stress has been linked to heightened allergy sensitivity in offspring. However, there is a notable absence of research on the mesovarium structure of offspring born from mothers subjected to cold stress during pregnancy. Understanding the impact of maternal cold stress on the mesovarium structure could provide valuable insights into reproductive health outcomes in offspring. Objective: This study aims to investigate structural changes in the mesovarium of offspring born from cold-stress affected rats. Material and Methods: 20 female Westar rats weighing around 200g were chosen and evenly divided into four containers; then, 2-3 male rats were introduced to each container. The Papanicolaou method was used to estimate the spermatozoa and estrus period from vaginal swabs taken from female rats at 8:00 a.m. Female rats examined with the presence of spermatozoa during the estrous phase of the estrous cycle are defined as pregnant. Pregnant rats are divided into experimental and control groups. The experimental group was stressed using the model of severe and chronic cold stress for 30 days. They were exposed to cold stress for 3 hours each morning between 8:00 and 11:00 o’clock at a temperature of minus 15 degrees Celsius. The control group was kept under normal laboratory conditions. Newborn female rats from both experimental and control groups were selected. At 2 months of age, rats were euthanized by decapitation, and their mesovaria were collected. Tissues were fixed in 4% formalin, embedded in paraffin, and sectioned into 5μm thick slices. The sections were stained with H&E and digitized by digital microscope. The area of brown fat and inflammatory infiltrations were quantified using Image J software. The blood cortisol levels were measured using ELISA. Data are expressed as the mean ± standard error of the mean (SEM). The Mann-Whitney test was used to compare the two groups. All analyses were performed using Prism (GraphPad Software). A p-value of < 0.05 was considered statistically significant. Result: Offspring born from stressed mothers exhibited significant physiological differences compared to the control group. Specifically, the body weight of offspring from stressed mothers was significantly lower than the control group (p=0.0002). Conversely, the cortisol level in offspring from stressed mothers was significantly higher (p=0.0446). Offspring born from stressed mothers showed a statistically significant increase in brown fat area compared to the control group (p=0.01). Additionally, offspring from stressed mothers had a significantly higher number of inflammatory infiltrates in their mesovarium compared to the control group (p<0.047). These results indicate the profound impact of maternal stress on offspring physiology, affecting body weight, stress hormone levels, metabolic characteristics, and inflammatory responses. Conclusion: Exposure to cold stress during pregnancy has significant repercussions on offspring physiology. Our findings demonstrate that cold stress exposure leads to increased blood cortisol levels, brown fat accumulation, and inflammatory cell infiltration in offspring. These results underscore the profound impact of maternal stress on offspring health and highlight the importance of mitigating environmental stressors during pregnancy to promote optimal offspring outcomes.

Keywords: brown fat, cold stress during pregnancy, inflammation, mesovarium

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78 Transformation of Bangladesh Society: The Role of Religion

Authors: Abdul Wohab

Abstract:

Context: The role of religion in the transformation of Bangladesh society has been significant since 1975. There has been a rise in religious presence, particularly Islam, in both private and public spheres supported by the state apparatuses. In 2009, a 'secular' political party came into power for the second time since independence and initiated the modernization of religious education systems. This research focuses on the transformation observed among the educated middle class who now prefer their children to attend modern, English medium madrasas that offer both religion-based and secular education. Research Aim: This research aims to investigate two main questions: a) what motivates the educated middle class to send their children to madrasa education? b) To what extent can it be argued that Bangladeshi society is transforming from its secular nature to being more religious?Methodology: The research applies a combination of primary and secondary methods. Case studies serve as the primary method, allowing for an in-depth exploration of the motivations of the educated middle class. The secondary method involves analyzing published news articles, op-eds, and websites related to madrasa education, as well as studying the reading syllabus of Aliya and Qwami madrasas in Bangladesh. Findings: Preliminary findings indicate that the educated middle class chooses madrasa education for reasons such as remembering and praying for their departed relatives, keeping their children away from substance abuse, fostering moral and ethical values, and instilling respect for seniors and relatives. The research also reveals that religious education is believed to help children remain morally correct according to the Quran and Hadith. Additionally, the establishment of madrasas in Bangladesh is attributed to economic factors, with demand and supply mechanisms playing a significant role. Furthermore, the findings suggest that government-run primary education institutions in rural areas face more challenges in enrollment compared to religious educational institutions like madrasas. Theoretical Importance: This research contributes to the understanding of societal transformation and the role of religion in this process. By examining the case of Bangladesh, it provides insights into how religion influences education choices and societal values. Data Collection and Analysis Procedures: Data for this research is collected through case studies, including interviews and observations of educated middle-class families who send their children to madrasas. In addition, analysis is conducted on relevant published materials such as news articles, op-eds, and websites. The reading syllabus of Aliya and Qwami madrasas is also analyzed to gain a comprehensive understanding of the education system. Questions Addressed: The research addresses two questions: a) what motivates the educated middle class to choose madrasa education for their children? b) To what extent can it be argued that Bangladeshi society is transforming from its secular nature to being more religious?Conclusion: The preliminary findings of this research highlight the motivations of the educated middle class in opting for madrasa education, including the desire to maintain religious traditions, promote moral values, and provide a strong foundation for their children. It also suggests that Bangladeshi society is experiencing a transformation towards a more religious orientation. This research contributes to the understanding of societal changes and the role of religion within Bangladesh, shedding light on the complex dynamics between religion and education.

Keywords: madrasa education, transformation, Bangladesh, religion and society, education

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77 A Study on Economic Impacts of Entrepreneurial Firms and Self-Employment: Minority Ethnics in Putatan, Penampang, Inanam, Menggatal, Uitm, Tongod, Sabah, Malaysia

Authors: Lizinis Cassendra Frederick Dony, Jirom Jeremy Frederick Dony, Andrew Nicholas, Dewi Binti Tajuddin

Abstract:

Starting and surviving a business is influenced by various entrepreneurship socio-economics activities. The study revealed that some of the entrepreneurs are not registered under SME but running own business as an intermediary with the private organization entrusted as “Self-Employed.” SME is known as “Small Medium Enterprise” contributes growth in Malaysia. Therefore, the entrepreneurialism business interest and entrepreneurial intention enhancing new spurring production, expanding employment opportunities, increasing productivity, promoting exports, stimulating innovation and providing new avenue in the business market place. This study has identified the unique contribution to the full understanding of complex mechanisms through entrepreneurship obstacles and education impacts on happiness and well-being to society. Moreover, “Ethnic” term has defined as a curious meaning refers to a classification of a large group of people customs implies to ancestral, racial, national, tribal, religious, linguistic and cultural origins. It is a social phenomenon.1 According to Sabah data population is amounting to 2,389,494 showed the predominant ethnic group being the Kadazan Dusun (18.4%) followed by Bajau (17.3%) and Malays (15.3%). For the year 2010, data statistic immigrants population report showed the amount to 239,765 people which cover 4% of the Sabahan’s population.2 Sabah has numerous group of talented entrepreneurs. The business environment among the minority ethnics are influenced with the business sentiment competition. The literature on ethnic entrepreneurship recognizes two main type entrepreneurships: the middleman and enclave entrepreneurs. According to Adam Smith,3 there are evidently some principles disposition to admire and maintain the distinction business rank status and cause most universal business sentiments. Due to credit barriers competition, the minority ethnics are losing the business market and since 2014, many illegal immigrants have been found to be using permits of the locals to operate businesses in Malaysia.4 The development of small business entrepreneurship among the minority ethnics in Sabah evidenced based variety of complex perception and differences concepts. The studies also confirmed the effects of heterogeneity on group decision and thinking caused partly by excessive pre-occupation with maintaining cohesiveness and the presence of cultural diversity in groups should reduce its probability.5 The researchers proposed that there are seven success determinants particularly to determine the involvement of minority ethnics comparing to the involvement of the immigrants in Sabah. Although, (SMEs) have always been considered the backbone of the economy development, the minority ethnics are often categorized it as the “second-choice.’ The study showed that illegal immigrants entrepreneur imposed a burden on Sabahan social programs as well as the prison, court and health care systems. The tension between the need for cheap labor and the impulse to protect Malaysian in Sabah workers, entrepreneurs and taxpayers, among the subjects discussed in this study. This is clearly can be advantages and disadvantages to the Sabah economic development.

Keywords: entrepreneurial firms, self-employed, immigrants, minority ethnic, economic impacts

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76 Early Predictive Signs for Kasai Procedure Success

Authors: Medan Isaeva, Anna Degtyareva

Abstract:

Context: Biliary atresia is a common reason for liver transplants in children, and the Kasai procedure can potentially be successful in avoiding the need for transplantation. However, it is important to identify factors that influence surgical outcomes in order to optimize treatment and improve patient outcomes. Research aim: The aim of this study was to develop prognostic models to assess the outcomes of the Kasai procedure in children with biliary atresia. Methodology: This retrospective study analyzed data from 166 children with biliary atresia who underwent the Kasai procedure between 2002 and 2021. The effectiveness of the operation was assessed based on specific criteria, including post-operative stool color, jaundice reduction, and bilirubin levels. The study involved a comparative analysis of various parameters, such as gestational age, birth weight, age at operation, physical development, liver and spleen sizes, and laboratory values including bilirubin, ALT, AST, and others, measured pre- and post-operation. Ultrasonographic evaluations were also conducted pre-operation, assessing the hepatobiliary system and related quantitative parameters. The study was carried out by two experienced specialists in pediatric hepatology. Comparative analysis and multifactorial logistic regression were used as the primary statistical methods. Findings: The study identified several statistically significant predictors of a successful Kasai procedure, including the presence of the gallbladder and levels of cholesterol and direct bilirubin post-operation. A detectable gallbladder was associated with a higher probability of surgical success, while elevated post-operative cholesterol and direct bilirubin levels were indicative of a reduced chance of positive outcomes. Theoretical importance: The findings of this study contribute to the optimization of treatment strategies for children with biliary atresia undergoing the Kasai procedure. By identifying early predictive signs of success, clinicians can modify treatment plans and manage patient care more effectively and proactively. Data collection and analysis procedures: Data for this analysis were obtained from the health records of patients who received the Kasai procedure. Comparative analysis and multifactorial logistic regression were employed to analyze the data and identify significant predictors. Question addressed: The study addressed the question of identifying predictive factors for the success of the Kasai procedure in children with biliary atresia. Conclusion: The developed prognostic models serve as valuable tools for early detection of patients who are less likely to benefit from the Kasai procedure. This enables clinicians to modify treatment plans and manage patient care more effectively and proactively. Potential limitations of the study: The study has several limitations. Its retrospective nature may introduce biases and inconsistencies in data collection. Being single centered, the results might not be generalizable to wider populations due to variations in surgical and postoperative practices. Also, other potential influencing factors beyond the clinical, laboratory, and ultrasonographic parameters considered in this study were not explored, which could affect the outcomes of the Kasai operation. Future studies could benefit from including a broader range of factors.

Keywords: biliary atresia, kasai operation, prognostic model, native liver survival

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75 Biosynthesis of a Nanoparticle-Antibody Phthalocyanine Photosensitizer for Use in Targeted Photodynamic Therapy of Cervical Cancer

Authors: Elvin P. Chizenga, Heidi Abrahamse

Abstract:

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

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

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74 Investigation of Chemical Effects on the Lγ2,3 and Lγ4 X-ray Production Cross Sections for Some Compounds of 66dy at Photon Energies Close to L1 Absorption-edge Energy

Authors: Anil Kumar, Rajnish Kaur, Mateusz Czyzycki, Alessandro Migilori, Andreas Germanos Karydas, Sanjiv Puri

Abstract:

The radiative decay of Li(i=1-3) sub-shell vacancies produced through photoionization results in production of the characteristic emission spectrum comprising several X-ray lines, whereas non-radiative vacancy decay results in Auger electron spectrum. Accurate reliable data on the Li(i=1-3) sub-shell X-ray production (XRP) cross sections is of considerable importance for investigation of atomic inner-shell ionization processes as well as for quantitative elemental analysis of different types of samples employing the energy dispersive X-ray fluorescence (EDXRF) analysis technique. At incident photon energies in vicinity of the absorption edge energies of an element, the many body effects including the electron correlation, core relaxation, inter-channel coupling and post-collision interactions become significant in the photoionization of atomic inner-shells. Further, in case of compounds, the characteristic emission spectrum of the specific element is expected to get influenced by the chemical environment (coordination number, oxidation state, nature of ligand/functional groups attached to central atom, etc.). These chemical effects on L X-ray fluorescence parameters have been investigated by performing the measurements at incident photon energies much higher than the Li(i=1-3) sub-shell absorption edge energies using EDXRF spectrometers. In the present work, the cross sections for production of the Lk(k= γ2,3, γ4) X-rays have been measured for some compounds of 66Dy, namely, Dy2O3, Dy2(CO3)3, Dy2(SO4)3.8H2O, DyI2 and Dy metal by tuning the incident photon energies few eV above the L1 absorption-edge energy in order to investigate the influence of chemical effects on these cross sections in presence of the many body effects which become significant at photon energies close to the absorption-edge energies. The present measurements have been performed under vacuum at the IAEA end-station of the X-ray fluorescence beam line (10.1L) of ELETTRA synchrotron radiation facility (Trieste, Italy) using self-supporting pressed pellet targets (1.3 cm diameter, nominal thicknesses ~ 176 mg/cm2) of 66Dy compounds (procured from Sigma Aldrich) and a metallic foil of 66Dy (nominal thickness ~ 3.9 mg/cm2, procured from Good Fellow, UK). The present measured cross sections have been compared with theoretical values calculated using the Dirac-Hartree-Slater(DHS) model based fluorescence and Coster-Kronig yields, Dirac-Fock(DF) model based X-ray emission rates and two sets of L1 sub-shell photoionization cross sections based on the non-relativistic Hartree-Fock-Slater(HFS) model and those deduced from the self-consistent Dirac-Hartree-Fock(DHF) model based total photoionization cross sections. The present measured XRP cross sections for 66Dy as well as for its compounds for the L2,3 and L4 X-rays, are found to be higher by ~14-36% than the two calculated set values. It is worth to be mentioned that L2,3 and L4 X-ray lines are originated by filling up of the L1 sub-shell vacancies by the outer sub-shell (N2,3 and O2,3) electrons which are much more sensitive to the chemical environment around the central atom. The present observed differences between measured and theoretical values are expected due to combined influence of the many-body effects and the chemical effects.

Keywords: chemical effects, L X-ray production cross sections, Many body effects, Synchrotron radiation

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73 Synthesis and Properties of Poly(N-(sulfophenyl)aniline) Nanoflowers and Poly(N-(sulfophenyl)aniline) Nanofibers/Titanium dioxide Nanoparticles by Solid Phase Mechanochemical and Their Application in Hybrid Solar Cell

Authors: Mazaher Yarmohamadi-Vasel, Ali Reza Modarresi-Alama, Sahar Shabzendedara

Abstract:

Purpose/Objectives: The first purpose was synthesize Poly(N-(sulfophenyl)aniline) nanoflowers (PSANFLs) and Poly(N-(sulfophenyl)aniline) nanofibers/titanium dioxide nanoparticles ((PSANFs/TiO2NPs) by a solid-state mechano-chemical reaction and template-free method and use them in hybrid solar cell. Also, our second aim was to increase the solubility and the processability of conjugated nanomaterials in water through polar functionalized materials. poly[N-(4-sulfophenyl)aniline] is easily soluble in water because of the presence of polar groups of sulfonic acid in the polymer chain. Materials/Methods: Iron (III) chloride hexahydrate (FeCl3∙6H2O) were bought from Merck Millipore Company. Titanium oxide nanoparticles (TiO2, <20 nm, anatase) and Sodium diphenylamine-4-sulfonate (99%) were bought from Sigma-Aldrich Company. Titanium dioxide nanoparticles paste (PST-20T) was prepared from Sharifsolar Co. Conductive glasses coated with indium tin oxide (ITO) were bought from Xinyan Technology Co (China). For the first time we used the solid-state mechano-chemical reaction and template-free method to synthesize Poly(N-(sulfophenyl)aniline) nanoflowers. Moreover, for the first time we used the same technique to synthesize nanocomposite of Poly(N-(sulfophenyl)aniline) nanofibers and titanium dioxide nanoparticles (PSANFs/TiO2NPs) also for the first time this nanocomposite was synthesized. Examining the results of electrochemical calculations energy gap obtained by CV curves and UV–vis spectra demonstrate that PSANFs/TiO2NPs nanocomposite is a p-n type material that can be used in photovoltaic cells. Doctor blade method was used to creat films for three kinds of hybrid solar cells in terms of different patterns like ITO│TiO2NPs│Semiconductor sample│Al. In the following, hybrid photovoltaic cells in bilayer and bulk heterojunction structures were fabricated as ITO│TiO2NPs│PSANFLs│Al and ITO│TiO2NPs│PSANFs /TiO2NPs│Al, respectively. Fourier-transform infrared spectra, field emission scanning electron microscopy (FE-SEM), ultraviolet-visible spectra, cyclic voltammetry (CV) and electrical conductivity were the analysis that used to characterize the synthesized samples. Results and Conclusions: FE-SEM images clearly demonstrate that the morphology of the synthesized samples are nanostructured (nanoflowers and nanofibers). Electrochemical calculations of band gap from CV curves demonstrated that the forbidden band gap of the PSANFLs and PSANFs/TiO2NPs nanocomposite are 2.95 and 2.23 eV, respectively. I–V characteristics of hybrid solar cells and their power conversion efficiency (PCE) under 100 mWcm−2 irradiation (AM 1.5 global conditions) were measured that The PCE of the samples were 0.30 and 0.62%, respectively. At the end, all the results of solar cell analysis were discussed. To sum up, PSANFLs and PSANFLs/TiO2NPs were successfully synthesized by an affordable and straightforward mechanochemical reaction in solid-state under the green condition. The solubility and processability of the synthesized compounds have been improved compared to the previous work. We successfully fabricated hybrid photovoltaic cells of synthesized semiconductor nanostructured polymers and TiO2NPs as different architectures. We believe that the synthesized compounds can open inventive pathways for the development of other Poly(N-(sulfophenyl)aniline based hybrid materials (nanocomposites) proper for preparing new generation solar cells.

Keywords: mechanochemical synthesis, PSANFLs, PSANFs/TiO2NPs, solar cell

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72 Integrating Non-Psychoactive Phytocannabinoids and Their Cyclodextrin Inclusion Complexes into the Treatment of Glioblastoma

Authors: Kyriaki Hatziagapiou, Konstantinos Bethanis, Olti Nikola, Elias Christoforides, Eleni Koniari, Eleni Kakouri, George Lambrou, Christina Kanaka-Gantenbein

Abstract:

Glioblastoma multiforme (GBM) remains a serious health challenge, as current therapeutic modalities continue to yield unsatisfactory results, with the average survival rarely exceeding 1-2 years. Natural compounds still provide some of the most promising approaches for discovering new drugs. The non-psychotropic cannabidiol (CBD) deriving from Cannabis sativa L. provides such promise. CBD is endowed with anticancer, antioxidant, and genoprotective properties as established in vitro and in in vivo experiments. CBD’s selectivity towards cancer cells and its safe profile suggest its usage in cancer therapies. However, the bioavailability of oral CBD is low due to poor aqueous solubility, erratic gastrointestinal absorption, and significant first-pass metabolism, hampering its therapeutic potential and resulting in a variable pharmacokinetic profile. In this context, CBD can take great advantage of nanomedicine-based formulation strategies. Cyclodextrins (CDs) are cyclic oligosaccharides used in the pharmaceutical industry to incorporate apolar molecules inside their hydrophobic cavity, increasing their stability, water solubility, and bioavailability or decreasing their side effects. CBD-inclusion complexes with CDs could be a good strategy to improve its properties, like solubility and stability to harness its full therapeutic potential. The current research aims to study the potential cytotoxic effect of CBD and CBD-CDs complexes CBD-RMβCD (randomly methylated β-cyclodextrin) and CBD-HPβCD (hydroxypropyl-b-CD) on the A172 glioblastoma cell line. CBD is diluted in 10% DMSO, and CBD/CDs solutions are prepared by mixing solid CBD, solid CDs, and dH2O. For the biological assays, A172 cells are incubated at a range of concentrations of CBD, CBD-RMβCD and CBD-HPβCD, RMβCD, and HPβCD (0,03125-4 mg/ml) at 24, 48, and 72 hours. Analysis of cell viability after incubation with the compounds is performed with Alamar Blue viability assay. CBD’s dilution to DMSO 10% was inadequate, as crystals are observed; thus cytotoxicity experiments are not assessed. CBD’s solubility is enhanced in the presence of both CDs. CBD/CDs exert significant cytotoxicity in a dose and time-dependent manner (p < 0.005 for exposed cells to any concentration at 48, 72, and 96 hours versus cells not exposed); as their concentration and time of exposure increases, the reduction of resazurin to resofurin decreases, indicating a reduction in cell viability. The cytotoxic effect is more pronounced in cells exposed to CBD-HPβCD for all concentrations and time-points. RMβCD and HPβCD at the highest concentration of 4 mg/ml also exerted antitumor action per se since manifesting cell growth inhibition. The results of our study could afford the basis of research regarding the use of natural products and their inclusion complexes as anticancer agents and the shift to targeted therapy with higher efficacy and limited toxicity. Acknowledgments: The research is partly funded by ΙΚΥ (State Scholarships Foundation) – Post-doc Scholarships-Partnership Agreement 2014-2020.

Keywords: cannabidiol, cyclodextrins, glioblastoma, hydroxypropyl-b-Cyclodextrin, randomly-methylated-β-cyclodextrin

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71 Particle Size Characteristics of Aerosol Jets Produced by A Low Powered E-Cigarette

Authors: Mohammad Shajid Rahman, Tarik Kaya, Edgar Matida

Abstract:

Electronic cigarettes, also known as e-cigarettes, may have become a tool to improve smoking cessation due to their ability to provide nicotine at a selected rate. Unlike traditional cigarettes, which produce toxic elements from tobacco combustion, e-cigarettes generate aerosols by heating a liquid solution (commonly a mixture of propylene glycol, vegetable glycerin, nicotine and some flavoring agents). However, caution still needs to be taken when using e-cigarettes due to the presence of addictive nicotine and some harmful substances produced from the heating process. Particle size distribution (PSD) and associated velocities generated by e-cigarettes have significant influence on aerosol deposition in different regions of human respiratory tracts. On another note, low actuation power is beneficial in aerosol generating devices since it exhibits a reduced emission of toxic chemicals. In case of e-cigarettes, lower heating powers can be considered as powers lower than 10 W compared to a wide range of powers (0.6 to 70.0 W) studied in literature. Due to the importance regarding inhalation risk reduction, deeper understanding of particle size characteristics of e-cigarettes demands thorough investigation. However, comprehensive study on PSD and velocities of e-cigarettes with a standard testing condition at relatively low heating powers is still lacking. The present study aims to measure particle number count and size distribution of undiluted aerosols of a latest fourth-generation e-cigarette at low powers, within 6.5 W using real-time particle counter (time-of-flight method). Also, temporal and spatial evolution of particle size and velocity distribution of aerosol jets are examined using phase Doppler anemometry (PDA) technique. To the authors’ best knowledge, application of PDA in e-cigarette aerosol measurement is rarely reported. In the present study, preliminary results about particle number count of undiluted aerosols measured by time-of-flight method depicted that an increase of heating power from 3.5 W to 6.5 W resulted in an enhanced asymmetricity in PSD, deviating from log-normal distribution. This can be considered as an artifact of rapid vaporization, condensation and coagulation processes on aerosols caused by higher heating power. A novel mathematical expression, combining exponential, Gaussian and polynomial (EGP) distributions, was proposed to describe asymmetric PSD successfully. The value of count median aerodynamic diameter and geometric standard deviation laid within a range of about 0.67 μm to 0.73 μm, and 1.32 to 1.43, respectively while the power varied from 3.5 W to 6.5 W. Laser Doppler velocimetry (LDV) and PDA measurement suggested a typical centerline streamwise mean velocity decay of aerosol jet along with a reduction of particle sizes. In the final submission, a thorough literature review, detailed description of experimental procedure and discussion of the results will be provided. Particle size and turbulent characteristics of aerosol jets will be further examined, analyzing arithmetic mean diameter, volumetric mean diameter, volume-based mean diameter, streamwise mean velocity and turbulence intensity. The present study has potential implications in PSD simulation and validation of aerosol dosimetry model, leading to improving related aerosol generating devices.

Keywords: E-cigarette aerosol, laser doppler velocimetry, particle size distribution, particle velocity, phase Doppler anemometry

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