Search results for: somatic sequence mutations

Authors: Daniel José de Oliveira Ferreira, Juan Harold Sosa-Arnao, Bruno Cássio Moreira, Leonardo Paes Rangel, Song Won Park

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The comprehensive CFD models have been used to represent and study the heterogeneous combustion of biomass. In the present work, the operation of a global flue gas circuit in the sugar-cane bagasse combustion, from wind boxes below primary air grate supply, passing by bagasse insertion in swirl burners and boiler furnace, to boiler bank outlet is simulated. It uses five different meshes representing each part of this system located in sequence: wind boxes and grate, boiler furnace, swirl burners, super heaters and boiler bank. The model considers turbulence using standard k-ε, combustion using EDM, radiation heat transfer using DTM with 16 ray directions and bagasse particle tracking represented by Schiller-Naumann model. The results showed good agreement with expected behavior found in literature and equipment design. The more detailed results view in separated parts of flue gas system allows to observe some flow behaviors that cannot be represented by usual simplifications like bagasse supply under homogeneous axial and rotational vectors and others that can be represented using new considerations like the representation of 26 thousand grate orifices by 144 rectangular inlets.

Keywords: comprehensive CFD model, sugar-cane bagasse combustion, sugar-cane bagasse grate boiler, axial

Procedia PDF Downloads 472

Authors: Qiang Wang, Hongyang Yu

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Multi-human 3D pose estimation is a challenging task in computer vision, which aims to recover the 3D joint locations of multiple people from multi-view images. In contrast to traditional methods, which typically only use color (RGB) images as input, our approach utilizes both color and depth (D) information contained in RGB-D images. We also employ a transformer-based model as the backbone of our approach, which is able to capture long-range dependencies and has been shown to perform well on various sequence modeling tasks. Our method is trained and tested on the Carnegie Mellon University (CMU) Panoptic dataset, which contains a diverse set of indoor and outdoor scenes with multiple people in varying poses and clothing. We evaluate the performance of our model on the standard 3D pose estimation metrics of mean per-joint position error (MPJPE). Our results show that the transformer-based approach outperforms traditional methods and achieves competitive results on the CMU Panoptic dataset. We also perform an ablation study to understand the impact of different design choices on the overall performance of the model. In summary, our work demonstrates the effectiveness of using a transformer-based approach with RGB-D images for multi-human 3D pose estimation and has potential applications in real-world scenarios such as human-computer interaction, robotics, and augmented reality.

Keywords: multi-human 3D pose estimation, RGB-D images, transformer, 3D joint locations

Procedia PDF Downloads 80

Authors: Zhao Yang Liu, Jing Tao

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The Asian long-horned beetle, Anoplophora glabripennis (Motschulsky) (Coleoptera: Cerambycidae: Lamiinae), is a wood-borer and polyphagous xylophages native to Asia and killing healthy trees. As it causes serious danger to trees, the beetle has been paid close attention in the world. However, the genetic markers limited, especially microsatellite. In this study, 24 novel simple sequence repeat (SSR) molecular markers, a powerful tool for genetic diversity studies and linkage map construction, were developed and characterized from whole genome shotgun sequences. We developed SSR loci of 2 to 6 repeated and perfect units including 9895 points, the density of SSRs was found one SSR per 56.57 kb and the abundance of SSR was 0.02/kb, besides 140 types of repeats motifs were found. Half of the 48 pairs SSR primers (containing 4 di-, 7 tri-, 2 tetra- and 11 hexamers SSRs) we selected randomly from 1222 pairs of primers were polymorphism. The number of alleles for these markers in 48 individuals varied from 3 to 21 with an average of 7.71, the number of effective alleles ranged from 1.22 to 9.97 with an average of 3.54. Besides this, the polymorphic information content (PIC) ranged from 0.18 to 0.89 with a mean of 0.65, And Shannon's Information index (I) ranged from 0.46 to 2.62 with an average of 1.44. The results suggest that the method for screening of SSR in the whole genome is feasible and efficient. SSR markers developed in this study can be used for population genetic studies of A. glabripennis. Moreover, they may also be helpful for the development of microsatellites for other Coleoptera.

Keywords: SSR markers, Anoplophora glabripennis, genetic diversity, whole genome

Procedia PDF Downloads 389

Authors: Martin Leroux, Sylvain Brisebois

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Eating a meal is among the Activities of Daily Living, but it takes a lot of time and effort for people with physical or functional limitations. Dedicated technologies are cumbersome and not portable, while general-purpose assistive robots such as wheelchair-based manipulators are too hard to control for elaborate continuous motion like eating. Eating with such devices has not previously been automated, since there existed no description of a feeding motion for uncontrolled environments. In this paper, we introduce a feeding mode for assistive manipulators, including a mathematical description of trajectories for motions that are difficult to perform manually such as gathering and scooping food at a defined/desired pace. We implement these trajectories in a sequence of movements for a semi-automated feeding mode which can be controlled with a very simple 3-button interface, allowing the user to have control over the feeding pace. Finally, we demonstrate the feeding mode with a JACO robotic arm and compare the eating speed, measured in bites per minute of three eating methods: a healthy person eating unaided, a person with upper limb limitations or disability using JACO with manual control, and a person with limitations using JACO with the feeding mode. We found that the feeding mode allows eating about 5 bites per minute, which should be sufficient to eat a meal under 30min.

Keywords: assistive robotics, automated feeding, elderly care, trajectory design, human-robot interaction

Procedia PDF Downloads 162

Authors: Khodzhaberdi Allaberdiev

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Substituted phenols are widely used for the synthesis of advanced polycondensation polymers. In terms of the structure regularity and practical value of obtained polymers are of special interest the p-substituted phenols. The lanthanide induced shifts (LIS) of the aromatic ring and the OH protons by addition Eu(fod)3 to various p-substituted phenols in CDCL3 solvent were measured Nuclear Magnetic Resonance spectroscopy. A linear relationship has been observed between the LIS of protons (∆=δcomplex –δsubstrate) and Eu(fod)3/substrate molar ratios. The LIS protons of the investigated phenols decreases in the following order: ОН > ortho > meta. The LIS of these protons also depends on both steric and electronic effects of p-substituents. The effect on the LIS of protons steric hindrance of substituents by way of example p-substituted alkyl phenols was studied. Alkyl phenols exhibit pronounced europium- induced shifts, their sensitivity increasing in the order: CH3 > C2H5 > sym-C5H11 > tert-C5H11 > tert-C4H9, i.e. in parallel with decreasing steric hindrance. The influence steric hindrance p-substituents of phenols on the LIS of protons in sequence following decreases: OH> meta >ortho. Contrary to the expectations, it is found that the LIS of the ortho protons an excellent linear correlation with meta-substituent constants, σm for 14 p-substituted phenols: ∆H2, 6=8.165-9.896 σm (r2=0,999). Moreover, a linear correlation between the LIS of the ortho protons and ionization constants, РКa of p-substituted phenols has been revealed. Similarly, the linear relationships for the LIS of the meta and the OH protons were obtained. Use the LIS of the phenolic hydroxyl groups for linear relationships is necessary with care, because of the signal broadening of the OH protons. New constants may be determinate with unusual case by this approach.

Keywords: novel correlations, NMR spectroscopy, phenols, shift reagent

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Authors: Aniket Kumar, Jacob Peedicayil

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Major depressive disorder (MDD) is a common and important psychiatric disorder. Several clinical features of MDD suggest an epigenetic basis for its pathogenesis. Since epigenetics (heritable changes in gene expression not involving changes in DNA sequence) may underlie the pathogenesis of MDD, epigenetic drugs such as DNA methyltransferase inhibitors (DNMTi) and histone deactylase inhibitors (HDACi) may be useful for treating MDD. The available literature indexed in Pubmed on preclinical drug trials of epigenetic drugs for the treatment of MDD was investigated. The search terms we used were ‘depression’ or ‘depressive’ and ‘HDACi’ or ‘DNMTi’. Among epigenetic drugs, it was found that there were 3 preclinical trials using HDACi and 3 using DNMTi for the treatment of MDD. All the trials were conducted on rodents (mice or rats). The animal models of depression that were used were: learned helplessness-induced animal model, forced swim test, open field test, and the tail suspension test. One study used a genetic rat model of depression (the Flinders Sensitive Line). The HDACi that were tested were: sodium butyrate, compound 60 (Cpd-60), and valproic acid. The DNMTi that were tested were: 5-azacytidine and decitabine. Among the three preclinical trials using HDACi, all showed an antidepressant effect in animal models of depression. Among the 3 preclinical trials using DNMTi also, all showed an antidepressant effect in animal models of depression. Thus, epigenetic drugs, namely, HDACi and DNMTi, may prove to be useful in the treatment of MDD and merit further investigation for the treatment of this disorder.

Keywords: DNA methylation, drug discovery, epigenetics, major depressive disorder

Procedia PDF Downloads 187

Authors: Rachael Bentley, Callahan Gergen, Brodie Thiede

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Roadways have a significant impact on the environment in so far as they function as barriers to wildlife movement, both through road mortality and through resultant road avoidance. Roads have an im-mense presence worldwide, and it is predicted to increase substantially in the next thirty years. As roadways become even more common, it is important to consider their environmental impact, and to mitigate the negative effects which they have on wildlife and wildlife mobility. In a thorough analysis of several related studies, a common conclusion was that roads cause habitat fragmentation, which can lead split populations to evolve differently, for better or for worse. Though some populations adapted positively to roadways, becoming more resistant to road mortality, and more tolerant to noise and chemical contamination, many others experienced maladaptation, either due to chemical contamination in and around their environment, or because of genetic mutations from inbreeding when their population was fragmented too substantially to support a large enough group for healthy genetic exchange. Large mammals were especially susceptible to maladaptation from inbreed-ing, as they require larger areas to roam and therefore require even more space to sustain a healthy population. Regardless of whether a species evolved positively or negatively as a result of their proximity to a road, animals tended to avoid roads, making the genetic diversity from habitat fragmentation an exceedingly prevalent issue in the larger discussion of road ecology. Additionally, the consideration of solu-tions, such as overpasses and underpasses, is crucial to ensuring the long term survival of many wildlife populations. In studies addressing the effectiveness of overpasses and underpasses, it seemed as though animals adjusted well to these sorts of solutions, but strategic place-ment, as well as proper sizing, proper height, shelter from road noise, and other considerations were important in construction. When an underpass or overpass was well-built and well-shielded from human activity, animals’ usage of the structure increased significantly throughout its first five years, thus reconnecting previously divided populations. Still, these structures are costly and they are often unable to fully address certain issues such as light, noise, and contaminants from vehicles. Therefore, the need for further discussion of new, crea-tive solutions remains paramount. Roads are one of the most consistent and prominent features of today’s landscape, but their environmental impacts are largely overlooked. While roads are useful for connecting people, they divide landscapes and animal habitats. Therefore, further research and investment in possible solutions is necessary to mitigate the negative effects which roads have on wildlife mobility and to pre-vent issues from resultant habitat fragmentation.

Keywords: fences, habitat fragmentation, roadways, wildlife mobility

Procedia PDF Downloads 179

Authors: Kuo-Cheng Liu

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In the latest research efforts, the structures of the image in the spatial domain have been successfully analyzed and proved to deduce the visual masking for accurately estimating the visibility thresholds of the image. If the structural properties of the video sequence in the temporal domain are taken into account to estimate the temporal masking, the improvement and enhancement of the as-sessing spatio-temporal visibility thresholds are reasonably expected. In this paper, the temporal characteristics of human perception to the change in block structures on the time axis are analyzed. The temporal characteristics of human perception are represented in terms of the significant variation in block structures for the analysis of human visual system (HVS). Herein, the block structure in each frame is computed by combined the pattern masking and the contrast masking simultaneously. The contrast masking always overestimates the visibility thresholds of edge regions and underestimates that of texture regions, while the pattern masking is weak on a uniform background and is strong on the complex background with spatial patterns. Under considering the significant variation of block structures between successive frames, we extend the block structures of images in the spatial domain to that of video sequences in the temporal domain to analyze the relation between the inter-frame variation of structures and the temporal masking. Meanwhile, the subjective viewing test and the fair rating process are designed to evaluate the consistency of the temporal characteristics with the HVS under a specified viewing condition.

Keywords: temporal characteristic, block structure, pattern masking, contrast masking

Procedia PDF Downloads 413

Authors: Emmanuel Agunloye, Asterios Gavriilidis, Luca Mazzei

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Gold nanoparticles are commonly synthesized by reducing chloroauric acid with sodium citrate. This method, referred to as the citrate method, can produce spherical gold nanoparticles (NPs) in the size range 10-150 nm. Gold NPs of this size are useful in many applications. However, the NPs are usually polydisperse and irreproducible. A better understanding of the synthesis mechanisms is thus required. This work thoroughly investigated the only model that describes the synthesis. This model combines mass and population balance equations, describing the NPs synthesis through a sequence of chemical reactions. Chloroauric acid reacts with sodium citrate to form aurous chloride and dicarboxy acetone. The latter organizes aurous chloride in a nucleation step and concurrently degrades into acetone. The unconsumed precursor then grows the formed nuclei. However, depending on the pH, both the precursor and the reducing agent react differently thus affecting the synthesis. In this work, we investigated the model for different conditions of pH, temperature and initial reactant concentrations. To solve the model, we used Parsival, a commercial numerical code, whilst to test it, we considered various conditions studied experimentally by different researchers, for which results are available in the literature. The model poorly predicted the experimental data. We believe that this is because the model does not account for the acid-base properties of both chloroauric acid and sodium citrate.

Keywords: citrate method, gold nanoparticles, Parsival, population balance equations, Turkevich organizer theory

Procedia PDF Downloads 203

Authors: Suzan Abd El Majid, Menachem Bamberger, Alexander Katsman

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Two Al-4 wt. % Cu based alloys, A201 and A201+Si were investigated in the as-cast, solution treated and aged conditions. The addition of Si was used to improve the castability of the basic alloy. The all investigated alloys in the as-cast condition contained a eutectic structure along grain boundaries (GBs) with the composition Al-50at. %Cu that was found by HRSEM EDS. Addition of Si refined the grain structure and changed the amount of the eutectic regions, their size and shape. Additionally, the A201+Si microstructure contained Si rods and small amount of Al6Mn4Cu3Fe2Si-phase. Solution treatment (ST) at 550°C for ~ 20 hours resulted in a slight dissolution of the eutectic structure in the A201 alloy while substantial dissolution and change of the eutectic composition was detected in the A201+Si alloy. After ST, the A201alloy contained θ-Al2Cu, Al5Cu2Mn3 and Al9Cu7Mn3(Fe) phases associated to the GBs, while the ST A201+Si alloy contained θ-Al2Cu, Al6Mn4Cu3(Fe,Si) and Si94Mn3Al2Cu phases. Precipitation hardening during aging at 170°C was investigated for both alloys. The microhardness of the ST A201alloy increased during aging and reached the maximum value ~ 140 HV after 2 h of aging. Initial microhardness of the ST A201+Si alloy was distinctly higher than one of the ST A201 alloy, but it decreased during the first hour of aging, then increased and reached the same maximum value ~ 140 HV after ~ 4 h of aging. It was concluded that the Si addition influenced the precipitation sequence and slowed down the age hardening process. The Si induced grain refining and evolution of the eutectic structure during the heat treatments applied are discussed.

Keywords: A201 alloys, castability, microstructure, micro-hardness

Procedia PDF Downloads 292

Authors: F. Varga, Z. Liber, J. Jakše, A. Turudić, Z. Šatović, I. Radosavljević, N. Jeran, M. Grdiša

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Dalmatian pyrethrum (Tanacetum cinerariifolium (Trevir.) Sch. Bip.; Asteraceae), a source of the commercially dominant plant insecticide pyrethrin, is a species endemic to the eastern Adriatic. Genetic diversity of T. cinerariifolium was previously studied using amplified fragment length polymorphism (AFLP) markers. However, microsatellite markers (single sequence repeats - SSRs) are more informative because they are codominant, highly polymorphic, locus-specific, and more reproducible, and thus are most often used to assess the genetic diversity of plant species. Dalmatian pyrethrum is an outcrossing diploid (2n = 18) whose large genome size and high repeatability have prevented the success of the traditional approach to SSR markers development. The advent of next-generation sequencing combined with the specifically developed method recently enabled the development of, to the author's best knowledge, the first set of SSRs for genomic characterization of Dalmatian pyrethrum, which is essential from the perspective of plant genetic resources conservation. To evaluate the effectiveness of the developed SSR markers in genetic differentiation of Dalmatian pyrethrum populations, a preliminary genetic diversity study was conducted on 30 individuals from three geographically distinct natural populations in Croatia (northern Adriatic island of Mali Lošinj, southern Adriatic island of Čiovo, and Mount Biokovo) based on 12 SSR loci. Analysis of molecular variance (AMOVA) by randomization test with 10,000 permutations was performed in Arlequin 3.5. The average number of alleles per locus, observed and expected heterozygosity, probability of deviations from Hardy-Weinberg equilibrium, and inbreeding coefficient was calculated using GENEPOP 4.4. Genetic distance based on the proportion of common alleles (DPSA) was calculated using MICROSAT. Cluster analysis using the neighbor-joining method with 1,000 bootstraps was performed with PHYLIP to generate a dendrogram. The results of the AMOVA analysis showed that the total SSR diversity was 23% within and 77% between the three populations. A slight deviation from Hardy-Weinberg equilibrium was observed in the Mali Lošinj population. Allele richness ranged from 2.92 to 3.92, with the highest number of private alleles observed in the Mali Lošinj population (17). The average observed DPSA between 30 individuals was 0.557. The highest DPSA (0.875) was observed between several pairs of Dalmatian pyrethrum individuals from the Mali Lošinj and Mt. Biokovo populations, and the lowest between two individuals from the Čiovo population. Neighbor-joining trees, based on DPSA, grouped individuals into clusters according to their population affiliation. The separation of Mt. Biokovo clade was supported (bootstrap value 58%), which is consistent with the previous study on AFLP markers, where isolated populations from Mt. Biokovo differed from the rest of the populations. The developed SSR markers are an effective tool for assessing the genetic diversity and structure of natural Dalmatian pyrethrum populations. These preliminary results are encouraging for a future comprehensive study with a larger sample size across the species' range. Combined with the biochemical data, these highly informative markers could help identify potential genotypes of interest for future development of breeding lines and cultivars that are both resistant to environmental stress and high in pyrethrins. Acknowledgment: This work has been supported by the Croatian Science Foundation under the project ‘Genetic background of Dalmatian pyrethrum (Tanacetum cinerariifolium /Trevir./ Sch. Bip.) insecticidal potential’- (PyrDiv) (IP-06-2016-9034) and by project KK.01.1.1.01.0005, Biodiversity and Molecular Plant Breeding, at the Centre of Excellence for Biodiversity and Molecular Plant Breeding (CoE CroP-BioDiv), Zagreb, Croatia.

Keywords: Asteraceae, genetic diversity, genomic SSRs, NGS, pyrethrum, Tanacetum cinerariifolium

Procedia PDF Downloads 114

Authors: Sanjeev Kumar Shukla, Govind Singh, Prabhat Pant Shahzad Ahmad

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Background: Graves’ disease is an autoimmune disorder with a genetic predisposition, and CD40 plays a pathogenic role in various autoimmune diseases. A single nucleotide polymorphism at position –1 of the Kozak sequence of the 5 untranslated regions of the CD40 gene of exon 1 has been reported to be associated with the development of Graves’ Disease. Objective: The aim of the present study was to investigate whether CD40 gene polymorphism confers susceptibility to Graves’ disease in the Kumaon region. CD40 gene polymorphisms were studied in Graves’ Disease patients (n=50) and healthy control subjects without anti-thyroid autoantibodies or a family history of autoimmune disorders (n=50). Material and Method: CD40 gene polymorphisms were studied in fifty Graves’ Disease patients and fifty healthy control subjects. All samples were collected from STG Hospital, Haldwani, Nainital. A C/T polymorphism at position –1 of the CD40 gene was measured using the polymerase chain reaction-restriction fragment length polymorphism. Results: There was no significant difference in allele or genotype frequency of the CD40 SNP between Graves’ Disease and control subjects. There was a significant decrease in the TT genotype frequency in the Graves’ Disease patients who developed Graves’ Disease after 40 years old than those under 40 years of age. These data suggest that the SNP of the CD40 gene is associated with susceptibility to the later onset of Graves’ Disease. Conclusion: The CD40 gene was a different susceptibility gene for Graves’ Disease within certain families because it was both linked and associated with Graves’ Disease.

Keywords: autoimmune diseases, pathogenesis, diagnosis, therapy

Procedia PDF Downloads 51

Authors: Bakhtiar Azadbakht, Karim Adinehvand, Amin Sahebnasagh

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The purpose of this study was to evaluate dependence of PAGAT polymer gel dosimeter 1/T2 on different electron and photon energies as well as on different mean dose rates for a standard clinically used Co-60 therapy unit and an ELECTA linear accelerator. A multi echo sequence with 32 equidistant echoes was used for the evaluation of irradiated polymer gel dosimeters. The optimal post-manufacture irradiation and post imaging times were both determined to be one day. The sensitivity of PAGAT polymer gel dosimeter with irradiation of photon and electron beams was represented by the slope of calibration curve in the linear region measured for each modality. The response of PAGAT gel with photon and electron beams is very similar in the lower dose region. The R2-dose response was linear up to 30Gy. In electron beams the R2-dose response for doses less than 3Gy is not exact, but in photon beams the R2-dose response for doses less than 2Gy is not exact. Dosimeter energy dependence was studied for electron energies of 4, 12 and 18MeV and photon energies of 1.25, 4, 6 and 18MV. Dose rate dependence was studied in 6MeV electron beam and 6MV photon beam with the use of dose rates 80, 160, 240, 320, 400, and 480cGy/min. Evaluation of dosimeters were performed on Siemens Symphony, Germany 1.5T Scanner in the head coil. In this study no trend in polymer-gel dosimeter 1/T2 dependence was found on mean dose rate and energy for electron and photon beams.

Keywords: polymer gels, PAGAT gel, electron and photon beams, MRI

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Authors: Andriy Didenko, Zanin Kavazovic

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Engineering students often have certain difficulties in mastering major theoretical concepts in mathematical courses such as differential equations. Student projects were proposed to motivate students’ learning and can be used as a tool to promote students’ interest in the material. Authors propose a student project that includes the use of Microsoft Excel. This instructional tool is often overlooked by both educators and students. An integral component of the experimental part of such a project is the exploration of an interactive spreadsheet. The aim is to assist engineering students in better understanding of Euler’s method. This method is employed to numerically solve first order differential equations. At first, students are invited to select classic equations from a list presented in a form of a drop-down menu. For each of these equations, students can select and modify certain key parameters and observe the influence of initial condition on the solution. This will give students an insight into the behavior of the method in different configurations as solutions to equations are given in numerical and graphical forms. Further, students could also create their own equations by providing functions of their own choice and a variety of initial conditions. Moreover, they can visualize and explore the impact of the length of the time step on the convergence of a sequence of numerical solutions to the exact solution of the equation. As a final stage of the project, students are encouraged to develop their own spreadsheets for other numerical methods and other types of equations. Such projects promote students’ interest in mathematical applications and further improve their mathematical and programming skills.

Keywords: student project, Euler's method, spreadsheet, engineering education

Procedia PDF Downloads 135

Authors: Anshu Radha Aggarwal

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As per the Right to Education Act (RTE), 2009, every child in the age group of 6-14 years shall be admitted in a neighborhood school. All the Out of School Children identified have to be enrolled / mainstreamed in to age appropriate class and there-after be provided special training. This paper addresses issues emerging from provisions in the RTE Act that specifically refer to the enrolment of out-of school children into age appropriate classes and the requirement to provide special trainings that will enable this to take place. In the context of RTE Act, the Out-of-School Children are first enrolled in the formal school and then they are provided with Special Training through NRSTCs (Long Term / Short term basis). These centers are functioning in formal school campus itself. This paper specifies the role of special training centers (STC). It presents a re-envisioning of assessment that recognizes two principal functions of assessment, assessment for learning and assessment of learning, instead of the more familiar categories of formative, diagnostic, summative, and evaluative assessment. The use of these two functions of assessment highlights and emphasizes the role of special training centers (STC) to assess their level for giving them appropriate special training and to evaluate their improvement in learning level. Challenge of problem faced by teachers to do diagnostic assessment, including its place in the sequence of assessment procedures appropriate in identifying and addressing individual children’s learning difficulties are solved by special training centers (STC). It is important that assessment is used to identify children with learning difficulties at the earliest possible stage so that appropriate support and intervention can be put in place. So appropriate challenges with tools are presented here for their assessment at entry level and at completion level of primary children by special training centers (STC).

Keywords: right to education, assessment, challenges, out of school children

Procedia PDF Downloads 461

Authors: Alaa Abdellatif, Gabrièle Breda

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Background. Advanced therapy medicinal products (ATMPs) are innovative therapies that mainly target orphan diseases and high unmet medical needs. ATMP includes gene therapy medicinal products (GTMP), somatic cell therapy medicinal products (CTMP), and tissue-engineered therapies (TEP). Since legislation opened the way in 2007, 25 ATMPs have been approved in the EU, which is about the same amount as the U.S. Food and Drug Administration. However, not all of the ATMPs that have been approved have successfully reached the market and retained their approval. Objectives. We aim to understand all the factors limiting the market access to very promising therapies in a systemic approach, to be able to overcome these problems, in the future, with scientific, regulatory and commercial innovations. Further to recent reviews that focus either on specific countries, products, or dimensions, we will address all the challenges faced by ATMP development today. Methodology. We used mixed methods and a multi-level approach for data collection. First, we performed an updated academic literature review on ATMP development and their scientific and market access challenges (papers published between 2018 and April 2023). Second, we analyzed industry feedback from cell and gene therapy webinars and white papers published by providers and pharmaceutical industries. Finally, we established a comparative analysis of the regulatory guidelines published by EMA and the FDA for ATMP approval. Results: The main challenges in bringing these therapies to market are the high development costs. Developing ATMPs is expensive due to the need for specialized manufacturing processes. Furthermore, the regulatory pathways for ATMPs are often complex and can vary between countries, making it challenging to obtain approval and ensure compliance with different regulations. As a result of the high costs associated with ATMPs, challenges in obtaining reimbursement from healthcare payers lead to limited patient access to these treatments. ATMPs are often developed for orphan diseases, which means that the patient population is limited for clinical trials which can make it challenging to demonstrate their safety and efficacy. In addition, the complex manufacturing processes required for ATMPs can make it challenging to scale up production to meet demand, which can limit their availability and increase costs. Finally, ATMPs face safety and efficacy challenges: dangerous adverse events of these therapies like toxicity related to the use of viral vectors or cell therapy, starting material and donor-related aspects. Conclusion. As a result of our mixed method analysis, we found that ATMPs face a number of challenges in their development, regulatory approval, and commercialization and that addressing these challenges requires collaboration between industry, regulators, healthcare providers, and patient groups. This first analysis will help us to address, for each challenge, proper and innovative solution(s) in order to increase the number of ATMPs approved and reach the patients

Keywords: advanced therapy medicinal products (ATMPs), product development, market access, innovation

Procedia PDF Downloads 76

Authors: Linyu Wang, Jiahui Ma, Jianhong Xiang, Hanyu Jiang

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For the pilot design of the sparse channel estimation model in Multiple Input Multiple Output Orthogonal Frequency Division Multiplexing (MIMO-OFDM) systems, the observation matrix constructed according to the matrix cross-correlation criterion, total correlation criterion and other optimization criteria are not optimal, resulting in inaccurate channel estimation and high bit error rate at the receiver. This paper proposes a pilot design method combining high-power sum and high-power variance criteria, which can more accurately estimate the channel. First, the pilot insertion position is designed according to the high-power variance criterion under the condition of equal power. Then, according to the high power sum criterion, the pilot power allocation is converted into a cone programming problem, and the power allocation is carried out. Finally, the optimal pilot is determined by calculating the weighted sum of the high power sum and the high power variance. Compared with the traditional pilot frequency, under the same conditions, the constructed MIMO-OFDM system uses the optimal pilot frequency for channel estimation, and the communication bit error rate performance obtains a gain of 6~7dB.

Keywords: MIMO-OFDM, pilot optimization, compressed sensing, channel estimation

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Authors: Aleksandra Twarda, Dobrosława Krzemień, Grzegorz Dubin, Tad A. Holak

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Stabilin-2 belongs to the group of scavenger receptors and plays a crucial role in clearance of more than 10 ligands from the bloodstream, including hyaluronic acid, products of degradation of extracellular matrix and metabolic products. The Link domain, a defining feature of stabilin-2, has a sequence similar to Link domains in other hyaluronic acid receptors, such as CD44 or TSG-6, and is responsible for most of ligands binding. Present knowledge of signal transduction by stabilin-2, as well as ligands’ recognition and binding mechanism, is limited. Until now, no experimental structures have been solved for any segments of stabilin-2. It has recently been demonstrated that the stabilin-2 knock-out or blocking of the receptor by an antibody effectively opposes cancer metastasis by elevating the level of circulating hyaluronic acid. Moreover, loss of expression of stabilin-2 in a peri-tumourous liver correlates with increased survival. Solving of the crystal structure of stabilin-2 and elucidation of the binding mechanism of hyaluronic acid could enable the precise characterization of the interactions in the binding site. These results may allow for designing specific small-molecule inhibitors of stabilin-2 that could be used in cancer therapy. To carry out screening for crystallization of stabilin-2, we cloned constructs of the Link domain of various lengths with or without surrounding domains. The folding properties of the constructs were checked by nuclear magnetic resonance (NMR). It is planned to show the binding of hyaluronic acid to the Link domain using several biochemical methods, i.a. NMR, isothermal titration calorimetry and fluorescence polarization assay.

Keywords: stabilin-2, Link domain, X-ray crystallography, NMR, hyaluronic acid, cancer

Procedia PDF Downloads 403

Authors: Natália Maria Rego

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ALeibnizn-algebraGis aK-vector space endowed whit a n-linearbracket operation [-,…-] : GG … G→ Gsatisfying the fundamental identity, which can be expressed saying that the right multiplication map Ry2, …, ᵧₙ: Gn→ G, Rᵧ₂, …, ᵧₙn(ˣ¹, …, ₓₙ) = [[ˣ¹, …, ₓₙ], ᵧ₂, …, ᵧₙ], is a derivation. This structure, together with its skew-symmetric version, named as Lie n-algebra or Filippov algebra, arose in the setting of Nambumechanics, an n-ary generalization of the Hamiltonian mechanics. Thefirst goal of this work is to provide a characterization of various classes of central extensions of Leibniz n-algebras in terms of homological properties. Namely, Commutator extension, Quasi-commutator extension, Stem extension, and Stem cover. These kind of central extensions are characterized by means of the character of the map *(E): nHL1(G) → M provided by the five-term exact sequence in homology with trivial coefficients of Leibniz n-algebras associated to an extension E : 0 → M → K → G → 0. For a free presentation 0 →R→ F →G→ 0of a Leibniz n-algebra G,the term M(G) = (R[F,…n.., F])/[R, F,..n-1..,F] is called the Schur multiplier of G, which is a Baer invariant, i.e., it does not depend on the chosen free presentation, and it is isomorphic to the first Leibniz n-algebras homology with trivial coefficients of G. A central extension of Leibniz n-algebras is a short exact sequenceE : 0 →M→K→G→ 0such that [M, K,.. ⁿ⁻¹.., K]=0. It is said to be a stem extension if M⊆[G, .. n.., G]. Additionally, if the induced map M(K) → M(G) is the zero map, then the stem extension Eis said to be a stem cover. The second aim of this work is to analyze the interplay between stem covers of Leibniz n-algebras and the Schur multiplier. Concretely, in the case of finite-dimensional Leibniz n-algebras, we show the existence of coverings, and we prove that all stem covers with finite-dimensional Schur multiplier are isoclinic. Additionally, we characterize stem covers of perfect Leibniz n-algebras.

Keywords: leibniz n-algebras, central extensions, Schur multiplier, stem cover

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Authors: G. Cunningham, E. Cantor, X. Wu, F. Shen, G. Jiang, S. Philips, C. Bales, Y. Xiao, T. R. Cummins, J. C. Fehrenbacher, B. P. Schneider

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Background: Taxane-induced peripheral neuropathy (TIPN) is the most devastating survivorship issue for patients receiving therapy. Dose reductions due to TIPN in the curative setting lead to inferior outcomes for African American patients, as prior research has shown that this group is more susceptible to developing severe neuropathy. The mechanistic underpinnings of TIPN, however, have not been entirely elucidated. While it would be appealing to use primary tissue to study the development of TIPN, procuring nerves from patients is not realistically feasible, as nerve biopsies are painful and may result in permanent damage. Therefore, our laboratory has investigated paclitaxel-induced neuronal morphological and molecular changes using an ex vivo model of human-induced pluripotent stem cell (iPSC)-derived neurons. Methods: iPSCs are undifferentiated and endlessly dividing cells that can be generated from a patient’s somatic cells, such as peripheral blood mononuclear cells (PBMCs). We successfully reprogrammed PBMCs into iPSCs using the Erythroid Progenitor Reprograming Kit (STEMCell Technologiesᵀᴹ); pluripotency was verified by flow cytometry analysis. iPSCs were then induced into neurons using a differentiation protocol that bypasses the neural progenitor stage and uses selected small-molecule modulators of key signaling pathways (SMAD, Notch, FGFR1 inhibition, and Wnt activation). Results: Flow cytometry analysis revealed expression of core pluripotency transcription factors Nanog, Oct3/4 and Sox2 in iPSCs overlaps with commercially purchased pluripotent cell line UCSD064i-20-2. Trilineage differentiation of iPSCs was confirmed with immunofluorescent imaging with germ-layer-specific markers; Sox17 and ExoA2 for ectoderm, Nestin, and Pax6 for mesoderm, and Ncam and Brachyury for endoderm. Sensory neuron markers, β-III tubulin, and Peripherin were applied to stain the cells for the maturity of iPSC-derived neurons. Patch-clamp electrophysiology and calcitonin gene-related peptide (CGRP) release data supported the functionality of the induced neurons and provided insight into the timing for which downstream assays could be performed (week 4 post-induction). We have also performed a cell viability assay and fluorescence-activated cell sorting (FACS) using four cell-surface markers (CD184, CD44, CD15, and CD24) to select a neuronal population. At least 70% of the cells were viable in the isolated neuron population. Conclusion: We have found that these iPSC-derived neurons recapitulate mature neuronal phenotypes and demonstrate functionality. Thus, this represents a patient-derived ex vivo neuronal model to investigate the molecular mechanisms of clinical TIPN.

Keywords: chemotherapy, iPSC-derived neurons, peripheral neuropathy, taxane, paclitaxel

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Authors: Alice Carter, Lucy Dumbell, Lorna Cameron, Victoria Lewis

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The Olympic discipline of eventing is the triathlon of equestrian sport, consisting of dressage, cross-country and show jumping. Falls on the cross-country are common and can be serious even causing death to rider. Research identifies an increased risk of a fall with an increasing number of obstacles and for jumping efforts later in the course suggesting fatigue maybe a contributing factor. Advice based on anecdotal evidence suggests riders undertake strength and conditioning programs to improve their ‘core’, thus improving their ability to maintain and control their riding position. There is little empirical evidence to support this advice. Therefore, the aim of this study is to investigate truck muscle fatigue and cognitive function during a simulated jumping test. Eight adult riders participated in a riding test on a Racewood Event simulator for 10 minutes, over a continuous jumping programme. The SEMG activity of six trunk muscles were bilaterally measured at every minute, and normalised root mean squares (RMS) and median frequencies (MDF) were computed from the EMG power spectra. Visual analogue scales (VAS) measuring Fatigue and Pain levels and Cognitive Function ‘tapping’ tests were performed before and after the riding test. Average MDF values for all muscles differed significantly between each sampled minute (p = 0.017), however a consistent decrease from Minute 1 and Minute 9 was not found, suggesting the trunk muscles fatigued and then recovered as other muscle groups important in maintaining the riding position during dynamic movement compensated. Differences between the MDF and RMS of different muscles were highly significant (H=213.01, DF=5, p < 0.001), supporting previous anecdotal evidence that different trunk muscles carry out different roles of posture maintenance during riding. RMS values were not significantly different between the sampled minutes or between riders, suggesting the riding test produced a consistent and repeatable effect on the trunk muscles. MDF values differed significantly between riders (H=50.8, DF = 5, p < 0.001), suggesting individuals may experience localised muscular fatigue of the same test differently, and that other parameters of physical fitness should be investigated to provide conclusions. Lumbar muscles were shown to be important in maintaining the position, therefore physical training program should focus on these areas. No significant differences were found between pre- and post-riding test VAS Pain and Fatigue scores or cognitive function test scores, suggesting the riding test was not significantly fatiguing for participants. However, a near significant correlation was found between time of riding test and VAS Pain score (p = 0.06), suggesting somatic pain may be a limiting factor to performance. No other correlations were found between the factors of participant riding test time, VAS Pain and Fatigue, however a larger sample needs to be tested to improve statistical analysis. The findings suggest the simulator riding test was not sufficient to provoke fatigue in the riders, however foundations for future studies have been laid to enable methodologies in realistic eventing settings.

Keywords: eventing, fatigue, horse-rider, surface EMG, trunk muscles

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Authors: Han Xiao

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The development of nanomedicines has recently achieved several breakthroughs in the field of cancer treatment; however, the biocompatibility and targeted burst release of these medications remain a limitation, which leads to serious side effects and significantly narrows the scope of their applications. The self-assembly of intermediate filament protein (IFP) peptides was triggered by a hydrophobic cation drug 7-amino actinomycin D (7-AAD) to synthesize pH-activatable nanoparticles (NPs) that could simultaneously locate tumors and produce antitumor effects. The designed IFP peptide included a target peptide (arginine–glycine–aspartate), a negatively charged region, and an α-helix sequence. It also possessed the ability to encapsulate 7-AAD molecules through the formation of hydrogen bonds and hydrophobic interactions by a one-step method. 7-AAD molecules with excellent near-infrared fluorescence properties could be target delivered into tumor cells by NPs and released immediately in the acidic environments of tumors and endosome/lysosomes, ultimately inducing cytotoxicity by arresting the tumor cell cycle with inserted DNA. It is noteworthy that the IFP/7-AAD NPs tail vein injection approach demonstrated not only high tumor-targeted imaging potential, but also strong antitumor therapeutic effects in vivo. The proposed strategy may be used in the delivery of cationic antitumor drugs for precise imaging and cancer therapy.

Keywords: 7-amino actinomycin D, intermediate filament protein, nanoparticle, tumor image

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Authors: Jia Xue, Frederica G. Lamar, Siyu Lin, Jennifer G. Lamori, Samendra Sherchan

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Brackish water samples from Lake Pontchartrain in Louisiana were assessed for the presence of pathogenic amoeba Naegleria fowleri, which causes primary amoebic meningoencephalitis (PAM). In our study, quantitative polymerase chain reaction (qPCR) methods were used to determine N. fowleri, E. coli, and Enterococcus in water collected from Lake Pontchartrain. A total of 158 water samples were analyzed over the 10-month sampling period. Statistically significant positive correlation between water temperature and N. fowleri concentration was observed. N. fowleri target sequence was detected at 35.4% (56/158) of the water samples from ten sites around the Lake ranged from 11.6 GC/100 ml water to 457.8 GC/100 ml water. A single factor (ANOVA) analysis shows the average concentration of N. fowleri in summer (119.8 GC/100 ml) was significantly higher than in winter (58.6 GC/100 ml) (p < 0.01). Statistically significant positive correlations were found between N. fowleri and qPCR E. coli results and N. fowleri and colilert E. coli (culture method), respectively. A weak positive correlation between E. coli and Enterococcus was observed from both qPCR (r = 0.27, p < 0.05) and culture based method (r = 0.52, p < 0.05). Meanwhile, significant positive correlation between qPCR and culture based methods for E. coli (r = 0.30, p < 0.05) and Enterococcus concentration was observed (r = 0.26, p < 0.05), respectively. Future research is needed to determine whether sediment is a source of N. fowleri found in the water column.

Keywords: brackish water, Escherichia coli, Enterococcus, Naegleria fowleri, primary amoebic meningoencephalitis (PAM), qPCR

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Authors: Huda Ahmed Al Taisan

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This paper investigates a phonological phenomenon, which exhibits variation ‘alternation’ in terms of the uvular consonants [q] and [ʁ] in Hasawi Arabic. This dialect is spoken in Alahsa city, which is located in the Eastern province of Saudi Arabia. To the best of our knowledge, no such research has systematically studied this phenomenon in Hasawi Arabic dialect. This paper is significant because it fills the gap in the literature about this alternation phenomenon in this understudied dialect. A large amount of the data is extracted from several interviews the author has conducted with 10 participants, native speakers of the dialect, and complemented by additional forms from social media. The latter method of collecting the data adds to the significance of the research. The analysis of the data is carried out in Harmonic Serialism Optimality Theory (HS-OT), a version of the Optimality Theoretic (OT) framework, which holds that linguistic forms are the outcome of the interaction among violable universal constraints, and in the recent development of OT into a model that accounts for linguistic variation in harmonic derivational steps. This alternation process is assumed to be phonologically unconditioned and in free variation in other varieties of Arabic dialects in the area. The goal of this paper is to investigate whether this phenomenon is in free variation or governed, what governs this alternation between [q] and [ʁ] and whether the alternation is phonological or other linguistic constraints are in action. The results show that the [q] and [ʁ] alternation is not free and it occurs due to different assimilation processes. Positional, segmental sequence and vowel adjacency factors are in action in Hasawi Arabic.

Keywords: harmonic serialism, Hasawi, uvular, variation

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Authors: Suparmi, Sampurna

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Sodium nitrite which is widespread used as a color fixative and preservative in foods can increase oxidative stress and cause hemolytic anemia. Consumption of food supplement containing sufficient antioxidant, e.g. chlorophyll, reported can decrease these negative effects. This study was conducted to determine the effect of chlorophyll from Sauropus androgynus leaves on Malodialdehide (MDA) and ferritin level. Experimental research with post-test only control group design was conducted using 24 female mice strain Balb-c. Sodium nitrite 0.3 ml/head/day given during 18 days, while the chlorophyll or Cu-chlorophyllin as much as 0.7 ml/head/day given the following day for 14 days. The mean of MDA levels of blood plasma in the control group, NaNO2 induction, induction NaNO2 and chlorophyll of S. androgynus leaves, induction of NaNO2 and Cu-chlorophyllin from K-Liquid in sequence is 2.10±0.11mol/L, 3.44±0.38 mol/L, 2.31±0.18 mol/L, 2.31±0.13 mol/L, whilst the ferritin levels mean in each group is 62.71±6.42 ng/ml; 63.22±7.59 ng/ml; 67.45±8.03 ng/ml, and 64.74±7.80 ng/ml, respectively. Results of Mann Whitney test found no significant difference in MDA levels (p>0.05), while the One-Way Anova test result found no significant difference in ferritin levels between the groups of mice that received S. androgynus chlorophyll with a group of mice that received Cu-chlorophyllin after induction NaNO2 (p>0.05). This indicates that chlorophyll from S. androgynus leaves as effective as Cu-chlorophyllin in decrease of MDA levels and increase of ferritin levels. Chlorophyll from S. androgynus are potential as food supplement in anemic conditions caused by sodium nitrite consumptions.

Keywords: ferritin, MDA, chlorophyll, sodium nitrite

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Authors: Mia Bahar, Özlem Bozkurt

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Obsessive-compulsive disorder (OCD) is a typical, persistent, and long-lasting mental health condition in which a person experiences uncontrollable, recurrent thoughts (or "obsessions") and/or activities (or "compulsions") that they feel compelled to engage in repeatedly. Obsessive-compulsive disorder is both underdiagnosed and undertreated. It frequently manifests in a variety of medical settings and is persistent, expensive, and burdensome. Obsessive-compulsive neurosis was long believed to be a condition that offered valuable insight into the inner workings of the unconscious mind. Obsessive-compulsive disorder is now recognized as a prime example of a neuropsychiatric condition susceptible to particular pharmacotherapeutic and psychotherapy therapies and mediated by pathology in particular neural circuits. An obsessive-compulsive disorder which is called OCD, usually has two components, one cognitive and the other behavioral, although either can occur alone. Obsessions are often repetitive and intrusive thoughts that invade consciousness. These obsessions are incredibly hard to control or dismiss. People who have OCD often engage in rituals to reduce anxiety associated with intrusive thoughts. Once the ritual is formed, the person may feel extreme relief and be free from anxiety until the thoughts of contamination intrude once again. These thoughts are strengthened through a manifestation of negative reinforcement because they allow the person to avoid anxiety and obscurity. These thoughts are described as autogenous, meaning they most likely come from nowhere. These unwelcome thoughts are related to actions which we can describe as Thought Action Fusion. The thought becomes equated with an action, such as if they refuse to perform the ritual, something bad might happen, and so people perform the ritual to escape the intrusive thought. In almost all cases of OCD, the person's life gets extremely disturbed by compulsions and obsessions. Studies show OCD is an estimated 1.1% prevalence, making it a challenging issue with high co-morbidities with other issues like depressive episodes, panic disorders, and specific phobias. The first to reveal brain anomalies in OCD were numerous CT investigations, although the results were inconsistent. A few studies have focused on the orbitofrontal cortex (OFC), anterior cingulate gyrus (AC), and thalamus, structures also implicated in the pathophysiology of OCD by functional neuroimaging studies, but few have found consistent results. However, some studies have found abnormalities in the basal ganglion. There have also been some discussions that OCD might be genetic. OCD has been linked to families in studies of family aggregation, and findings from twin studies show that this relationship is somewhat influenced by genetic variables. Some Research has shown that OCD is a heritable, polygenic condition that can result from de novo harmful mutations as well as common and unusual variants. Numerous studies have also presented solid evidence in favor of a significant additive genetic component to OCD risk, with distinct OCD symptom dimensions showing both common and individual genetic risks.

Keywords: compulsions, obsessions, neuropsychiatric, genetic

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Authors: Morteza Haghi, Cigdem Yilmazbas, Ayse Zeynep Uysal, Melisa Tepedelen, Gozde Turkoz Bakirci

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Today, the increase in plastic waste accumulation is an inescapable consequence of environmental pollution; the disposal of these wastes has caused a significant problem. Variable methods have been utilized; however, biodegradation is the most environmentally friendly and low-cost method. Accordingly, the present study aimed to isolate the bacteria capable of biodegradation of plastics. In doing so, we applied the liquid carbon-free basal medium (LCFBM) prepared with deionized water for the isolation of bacterial species obtained from soil samples taken from the Izmir Menemen region. Isolates forming biofilms on plastic were selected and named (PLB3, PLF1, PLB1B) and subjected to a degradation test. FTIR analysis, 16s rDNA amplification, sequencing, identification of isolates were performed. Finally, at the end of the process, a mass loss of 16.6% in PLB3 isolate and 25% in PLF1 isolate was observed, while no mass loss was detected in PLB1B isolate. Only PLF1 and PLB1B created transparent zones on plastic texture. Considering the FTIR result, PLB3 changed plastic structure by 13.6% and PLF1 by 17%, while PLB1B did not change the plastic texture. According to the 16s rDNA sequence analysis, FLP1, PLB1B, and PLB3 isolates were identified as Streptomyces albogriseolus, Enterobacter cloacae, and Klebsiella pneumoniae, respectively.

Keywords: polyethylene, biodegradation, bacteria, 16s rDNA, FTIR

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Authors: Leonard Lipovich, Pattaraporn Thepsuwan, Anton-Scott Goustin, Juan Cai, Donghong Ju, James B. Brown

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Two-thirds of human genes do not encode any known proteins. Aside from long non-coding RNA (lncRNA) genes with recently-discovered functions, the ~40,000 non-protein-coding human genes remain poorly understood, and a role for their transcripts as de-facto unconventional messenger RNAs has not been formally excluded. Ribosome profiling (Riboseq) predicts translational potential, but without independent evidence of proteins from lncRNA open reading frames (ORFs), ribosome binding of lncRNAs does not prove translation. Previously, we mass-spectrometrically documented translation of specific lncRNAs in human K562 and GM12878 cells. We now examined lncRNA translation in human MCF7 cells, integrating strand-specific Illumina RNAseq, Riboseq, and deep mass spectrometry in biological quadruplicates performed at two core facilities (BGI, China; City of Hope, USA). We excluded known-protein matches. UCSC Genome Browser-assisted manual annotation of imperfect (tryptic-digest-peptides)-to-(lncRNA-three-frame-translations) alignments revealed three peptides hypothetically explicable by 'stop-to-nonstop' in-frame replacement of stop codons by amino acids in two ORFs of the lncRNA MMP24-AS1. To search for this phenomenon genomewide, we designed and implemented a novel pipeline, matching tryptic-digest spectra to wildcard-instead-of-stop versions of repeat-masked, six-frame, whole-genome translations. Along with singleton putative stop-to-nonstop events affecting four other lncRNAs, we identified 24 additional peptides with stop-to-nonstop in-frame substitutions from multiple positive-strand MMP24-AS1 ORFs. Only UAG and UGA, never UAA, stop codons were impacted. All MMP24-AS1-matching spectra met the same significance thresholds as high-confidence known-protein signatures. Targeted resequencing of MMP24-AS1 genomic DNA and cDNA from the same samples did not reveal any mutations, polymorphisms, or sequencing-detectable RNA editing. This unprecedented apparent gene-specific violation of the genetic code highlights the importance of matching peptides to whole-genome, not known-genes-only, ORFs in mass-spectrometry workflows, and suggests a new mechanism enhancing the combinatorial complexity of the proteome. Funding: NIH Director’s New Innovator Award 1DP2-CA196375 to LL.

Keywords: genetic code, lncRNA, long non-coding RNA, mass spectrometry, proteogenomics, ribo-seq, ribosome, RNAseq

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Authors: Mostafa Mohammadpour, Christoph Kapeller, Christy Li, Josef Scharinger, Christoph Guger

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Interictal spikes provide valuable information on electrocorticography (ECoG), which aids in surgical planning for patients who suffer from refractory epilepsy. However, the shape and temporal dynamics of these spikes remain unclear. The purpose of this work was to analyze the shape of interictal spikes and measure their distance to the seizure onset zone (SOZ) to use in epilepsy surgery. Thirteen patients' data from the iEEG portal were retrospectively studied. For analysis, half an hour of ECoG data was used from each patient, with the data being truncated before the onset of a seizure. Spikes were first detected and grouped in a sequence, then clustered into interictal epileptiform discharges (IEDs) and non-IED groups using two-step clustering. The distance of the spikes from IED and non-IED groups to SOZ was quantified and compared using the Wilcoxon rank-sum test. Spikes in the IED group tended to be in SOZ or close to it, while spikes in the non-IED group were in distance of SOZ or non-SOZ area. At the group level, the distribution for sharp wave, positive baseline shift, slow wave, and slow wave to sharp wave ratio was significantly different for IED and non-IED groups. The distance of the IED cluster was 10.00mm and significantly closer to the SOZ than the 17.65mm for non-IEDs. These findings provide insights into the shape and spatiotemporal dynamics of spikes that could influence the network mechanisms underlying refractory epilepsy.

Keywords: spike propagation, spike pattern, clustering, SOZ

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Authors: Cecilia Jatu, Adventino

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Gedangsari is located in Gunungkidul, Yogyakarta Province, which has several criteria to be used as a new geosite object. The research area is located in the southern mountain zone of Java, composed of 5 rock formations with Oligocene up to Middle Miocene age. The purpose of this study is to reveal the potential of geotourism and the geoheritage to be proposed as a new geosite and to make a geosite map of Gedangsari. The research method used is descriptive data collection and which includes quantitative geological data collection, geotourism, and heritage sites, then supported by petrographic analysis, geological structure, geological mapping, and SWOT analysis. The geological data proved that Gedangsari consists of igneous rock (intrusion), pyroclastic rock, and sediment rock. This condition caused many varieties and particular geomorphological platform. Geotourism that include in Gedangsari are Luweng Sampang Canyon, Gedangsari Bouma Sequence, Watugajah Columnar Joint, Gedangsari Marine Fan Sediment, and Tegalrejo Waterfall. There is also Tegalrejo Village, which can be considered as geoheritage site because of its culture and batik traditional cloth. The results of the SWOT analysis, Gedangsari geosite must be developed and appropriately promoted in order to improve the existence. The development of geosite area will have a significant impact that improve the economic growth of the surrounding community and can be used by the government as base information for sustainable development. In addition, the making of an educational map about the geological conditions and geotourism location of the Gedangsari geosite can increase the people's knowledge about Gedangsari.

Keywords: Gedangsari, geoheritage, geotourism, geosite

Procedia PDF Downloads 122