Search results for: functional infrared thermal imaging
462 Cognitive Decline in People Living with HIV in India and Correlation with Neurometabolites Using 3T Magnetic Resonance Spectroscopy (MRS): A Cross-Sectional Study
Authors: Kartik Gupta, Virendra Kumar, Sanjeev Sinha, N. Jagannathan
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Introduction: A significant number of patients having human immunodeficiency virus (HIV) infection show a neurocognitive decline (NCD) ranging from minor cognitive impairment to severe dementia. The possible causes of NCD in HIV-infected patients include brain injury by HIV before cART, neurotoxic viral proteins and metabolic abnormalities. In the present study, we compared the level of NCD in asymptomatic HIV-infected patients with changes in brain metabolites measured by using magnetic resonance spectroscopy (MRS). Methods: 43 HIV-positive patients (30 males and 13 females) coming to ART center of the hospital and HIV-seronegative healthy subjects were recruited for the study. All the participants completed MRI and MRS examination, detailed clinical assessments and a battery of neuropsychological tests. All the MR investigations were carried out at 3.0T MRI scanner (Ingenia/Achieva, Philips, Netherlands). MRI examination protocol included the acquisition of T2-weighted imaging in axial, coronal and sagittal planes, T1-weighted, FLAIR, and DWI images in the axial plane. Patients who showed any apparent lesion on MRI were excluded from the study. T2-weighted images in three orthogonal planes were used to localize the voxel in left frontal lobe white matter (FWM) and left basal ganglia (BG) for single voxel MRS. Single voxel MRS spectra were acquired with a point resolved spectroscopy (PRESS) localization pulse sequence at an echo time (TE) of 35 ms and a repetition time (TR) of 2000 ms with 64 or 128 scans. Automated preprocessing and determination of absolute concentrations of metabolites were estimated using LCModel by water scaling method and the Cramer-Rao lower bounds for all metabolites analyzed in the study were below 15\%. Levels of total N-acetyl aspartate (tNAA), total choline (tCho), glutamate + glutamine (Glx), total creatine (tCr), were measured. Cognition was tested using a battery of tests validated for Indian population. The cognitive domains tested were the memory, attention-information processing, abstraction-executive, simple and complex perceptual motor skills. Z-scores normalized according to age, sex and education standard were used to calculate dysfunction in these individual domains. The NCD was defined as dysfunction with Z-score ≤ 2 in at least two domains. One-way ANOVA was used to compare the difference in brain metabolites between the patients and healthy subjects. Results: NCD was found in 23 (53%) patients. There was no significant difference in age, CD4 count and viral load between the two groups. Maximum impairment was found in the domains of memory and simple motor skills i.e., 19/43 (44%). The prevalence of deficit in attention-information processing, complex perceptual motor skills and abstraction-executive function was 37%, 35%, 33% respectively. Subjects with NCD had a higher level of Glutamate in the Frontal region (8.03 ± 2.30 v/s. 10.26 ± 5.24, p-value 0.001). Conclusion: Among newly diagnosed, ART-naïve retroviral disease patients from India, cognitive decline was found in 53\% patients using tests validated for this population. Those with neurocognitive decline had a significantly higher level of Glutamate in the left frontal region. There was no significant difference in age, CD4 count and viral load at initiation of ART between the two groups.Keywords: HIV, neurocognitive decline, neurometabolites, magnetic resonance spectroscopy
Procedia PDF Downloads 211461 Fracture Behaviour of Functionally Graded Materials Using Graded Finite Elements
Authors: Mohamad Molavi Nojumi, Xiaodong Wang
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In this research fracture behaviour of linear elastic isotropic functionally graded materials (FGMs) are investigated using modified finite element method (FEM). FGMs are advantageous because they enhance the bonding strength of two incompatible materials, and reduce the residual stress and thermal stress. Ceramic/metals are a main type of FGMs. Ceramic materials are brittle. So, there is high possibility of crack existence during fabrication or in-service loading. In addition, damage analysis is necessary for a safe and efficient design. FEM is a strong numerical tool for analyzing complicated problems. Thus, FEM is used to investigate the fracture behaviour of FGMs. Here an accurate 9-node biquadratic quadrilateral graded element is proposed in which the influence of the variation of material properties is considered at the element level. The stiffness matrix of graded elements is obtained using the principle of minimum potential energy. The implementation of graded elements prevents the forced sudden jump of material properties in traditional finite elements for modelling FGMs. Numerical results are verified with existing solutions. Different numerical simulations are carried out to model stationary crack problems in nonhomogeneous plates. In these simulations, material variation is supposed to happen in directions perpendicular and parallel to the crack line. Two special linear and exponential functions have been utilized to model the material gradient as they are mostly discussed in literature. Also, various sizes of the crack length are considered. A major difference in the fracture behaviour of FGMs and homogeneous materials is related to the break of material symmetry. For example, when the material gradation direction is normal to the crack line, even under applying the mode I loading there exists coupled modes I and II of fracture which originates from the induced shear in the model. Therefore, the necessity of the proper modelling of the material variation should be considered in capturing the fracture behaviour of FGMs specially, when the material gradient index is high. Fracture properties such as mode I and mode II stress intensity factors (SIFs), energy release rates, and field variables near the crack tip are investigated and compared with results obtained using conventional homogeneous elements. It is revealed that graded elements provide higher accuracy with less effort in comparison with conventional homogeneous elements.Keywords: finite element, fracture mechanics, functionally graded materials, graded element
Procedia PDF Downloads 174460 Tertiary Level Teachers' Beliefs about Codeswitching
Authors: Hoa Pham
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Code switching, which can be described as the use of students’ first language in second language classrooms, has long been a controversial topic in the area of language teaching and second language acquisition. While this has been widely investigated across different contexts, little empirical research has been undertaken in Vietnam. The findings of this study contribute to our understanding of bilingual discourse and code switching practices in content and language integrated classrooms, which has significant implications for language teaching and learning in general and in particular for language pedagogy at tertiary level in Vietnam. This study examines the accounts the teachers articulated for their code switching practices in content-based Business English in Vietnam. Data were collected from five teachers through the use of stimulated recall interviews facilitated by the video data to garner the teachers' cognitive reflection, and allowed them to vocalise the motivations behind their code switching behaviour in particular contexts. The literature has recommended that when participants are provided with a large amount of stimuli or cues, they will experience an original situation again in their imagination with great accuracy. This technique can also provide a valuable "insider" perspective on the phenomenon under investigation which complements the researcher’s "outsider" observation. This can create a relaxed atmosphere during the interview process, which in turn promotes the collection of rich and diverse data. Also, participants can be empowered by this technique as they can raise their own concerns and discuss instances which they find important or interesting. The data generated through this study were analysed using a constant comparative approach. The study found that the teachers indicated their support for the use of code switching in their pedagogical practices. Particularly, as a pedagogical resource, the teachers saw code switching to the L1 playing a key role in facilitating the students' comprehension of both content knowledge and the target language. They believed the use of the L1 accommodates the students' current language competence and content knowledge. They also expressed positive opinions about the role that code switching plays in stimulating students' schematic language and content knowledge, encouraging retention and interest in learning and promoting a positive affective environment in the classroom. The teachers perceived that their use of code switching to the L1 helps them meet the students' language needs and prepares them for their study in subsequent courses and addresses functional needs so that students can cope with English language use outside the classroom. Several factors shaped the teachers' perceptions of their code switching practices, including their accumulated teaching experience, their previous experience as language learners, their theoretical understanding of language teaching and learning, and their knowledge of the teaching context. Code switching was a typical phenomenon in the observed classes and was supported by the teachers in certain contexts. This study reinforces the call in the literature to recognise this practice as a useful instructional resource.Keywords: codeswitching, language teaching, teacher beliefs, tertiary level
Procedia PDF Downloads 451459 Enhancement of Cross-Linguistic Effect with the Increase in the Multilingual Proficiency during Early Childhood: A Case Study of English Language Acquisition by a Pre-School Child
Authors: Anupama Purohit
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The paper is a study on the inevitable cross-linguistic effect found in the early multilingual learners. The cross-linguistic behaviour like code-mixing, code-switching, foreign accent, literal translation, redundancy and syntactic manipulation effected due to other languages on the English language output of a non-native pre-school child are discussed here. A case study method is adopted in this paper to support the claim of the title. A simultaneously tetra lingual pre-school child’s (within 1;3 to 4;0) language behaviour is analysed here. The sample output data of the child is gathered from the diary entries maintained by her family, regular observations and video recordings done since her birth. She is getting the input of her mother tongue, Sambalpuri, from her grandparents only; Hindi, the local language from her play-school and the neighbourhood; English only from her mother and occasional visit of other family friends; Odia only during the reading of the Odia story book. The child is exposed to code-mixing of all the languages throughout her childhood. But code-mixing, literal translation, redundancy and duplication were absent in her initial stage of multilingual acquisition. As the child was more proficient in English in comparison to her other first languages and had never heard code-mixing in English language; it was expected from her input pattern of English (one parent, English language) that she would maintain purity in her use of English while talking to the English language interlocutor. But with gradual increase in the language proficiency in each of the languages of the child, her handling of the multiple codes becomes deft cross-linguistically. It can be deduced from the case study that after attaining certain milestone proficiency in each language, the child’s linguistic faculty can operate at a metalinguistic level. The functional use of each morpheme, their arrangement in words and in the sentences, the supra segmental features, lexical-semantic mapping, culture specific use of a language and the pragmatic skills converge to give a typical childlike multilingual output in an intelligible manner to the multilingual people (with the same set of languages in combination). The result is appealing because for expressing the same ideas which the child used to speak (may be with grammatically wrong expressions) in one language, gradually, she starts showing cross-linguistic effect in her expressions. So the paper pleads for the separatist view from the very beginning of the holophrastic phase (as the child expresses in addressee-specific language); but development of a metalinguistic ability that helps the child in communicating in a sophisticated way according to the linguistic status of the addressee is unique to the multilingual child. This metalinguistic ability is independent of the mode if input of a multilingual child.Keywords: code-mixing, cross-linguistic effect, early multilingualism, literal translation
Procedia PDF Downloads 299458 Formation of the Water Assisted Supramolecular Assembly in the Transition Structure of Organocatalytic Asymmetric Aldol Reaction: A DFT Study
Authors: Kuheli Chakrabarty, Animesh Ghosh, Atanu Roy, Gourab Kanti Das
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Aldol reaction is an important class of carbon-carbon bond forming reactions. One of the popular ways to impose asymmetry in aldol reaction is the introduction of chiral auxiliary that binds the approaching reactants and create dissymmetry in the reaction environment, which finally evolves to enantiomeric excess in the aldol products. The last decade witnesses the usage of natural amino acids as chiral auxiliary to control the stereoselectivity in various carbon-carbon bond forming processes. In this context, L-proline was found to be an effective organocatalyst in asymmetric aldol additions. In last few decades the use of water as solvent or co-solvent in asymmetric organocatalytic reaction is increased sharply. Simple amino acids like L-proline does not catalyze asymmetric aldol reaction in aqueous medium not only that, In organic solvent medium high catalytic loading (~30 mol%) is required to achieve moderate to high asymmetric induction. In this context, huge efforts have been made to modify L-proline and 4-hydroxy-L-proline to prepare organocatalyst for aqueous medium asymmetric aldol reaction. Here, we report the result of our DFT calculations on asymmetric aldol reaction of benzaldehyde, p-NO2 benzaldehyde and t-butyraldehyde with a number of ketones using L-proline hydrazide as organocatalyst in wet solvent free condition. Gaussian 09 program package and Gauss View program were used for the present work. Geometry optimizations were performed using B3LYP hybrid functional and 6-31G(d,p) basis set. Transition structures were confirmed by hessian calculation and IRC calculation. As the reactions were carried out in solvent free condition, No solvent effect were studied theoretically. Present study has revealed for the first time, the direct involvement of two water molecules in the aldol transition structures. In the TS, the enamine and the aldehyde is connected through hydrogen bonding by the assistance of two intervening water molecules forming a supramolecular network. Formation of this type of supramolecular assembly is possible due to the presence of protonated -NH2 group in the L-proline hydrazide moiety, which is responsible for the favorable entropy contribution to the aldol reaction. It is also revealed from the present study that, water assisted TS is energetically more favorable than the TS without involving any water molecule. It can be concluded from this study that, insertion of polar group capable of hydrogen bond formation in the L-proline skeleton can lead to a favorable aldol reaction with significantly high enantiomeric excess in wet solvent free condition by reducing the activation barrier of this reaction.Keywords: aldol reaction, DFT, organocatalysis, transition structure
Procedia PDF Downloads 433457 Enhanced Stability of Piezoelectric Crystalline Phase of Poly(Vinylidene Fluoride) (PVDF) and Its Copolymer upon Epitaxial Relationships
Authors: Devi Eka Septiyani Arifin, Jrjeng Ruan
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As an approach to manipulate the performance of polymer thin film, epitaxy crystallization within polymer blends of poly(vinylidene fluoride) (PVDF) and its copolymer poly(vinylidene fluoride-trifluoroethylene) P(VDF-TrFE) was studied in this research, which involves the competition between phase separation and crystal growth of constitutive semicrystalline polymers. The unique piezoelectric feature of poly(vinylidene fluoride) crystalline phase is derived from the packing of molecular chains in all-trans conformation, which spatially arranges all the substituted fluorene atoms on one side of the molecular chain and hydrogen atoms on the other side. Therefore, the net dipole moment is induced across the lateral packing of molecular chains. Nevertheless, due to the mutual repulsion among fluorene atoms, this all-trans molecular conformation is not stable, and ready to change above curie temperature, where thermal energy is sufficient to cause segmental rotation. This research attempts to explore whether the epitaxial interactions between piezoelectric crystals and crystal lattice of hexamethylbenzene (HMB) crystalline platelet is able to stabilize this metastable all-trans molecular conformation or not. As an aromatic crystalline compound, the melt of HMB was surprisingly found able to dissolve the poly(vinylidene fluoride), resulting in homogeneous eutectic solution. Thus, after quenching this binary eutectic mixture to room temperature, subsequent heating or annealing processes were designed to explore the involve phase separation and crystallization behavior. The phase transition behaviors were observed in-situ by X-ray diffraction and differential scanning calorimetry (DSC). The molecular packing was observed via transmission electron microscope (TEM) and the principles of electron diffraction were brought to study the internal crystal structure epitaxially developed within thin films. Obtained results clearly indicated the occurrence of heteroepitaxy of PVDF/PVDF-TrFE on HMB crystalline platelet. Both the concentration of poly(vinylidene fluoride) and the mixing ratios of these two constitutive polymers have been adopted as the influential factors for studying the competition between the epitaxial crystallization of PVDF and P(VDF-TrFE) on HMB crystalline. Furthermore, the involved epitaxial relationship is to be deciphered and studied as a potential factor capable of guiding the wide spread of piezoelectric crystalline form.Keywords: epitaxy, crystallization, crystalline platelet, thin film and mixing ratio
Procedia PDF Downloads 222456 Study of Biofouling Wastewater Treatment Technology
Authors: Sangho Park, Mansoo Kim, Kyujung Chae, Junhyuk Yang
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The International Maritime Organization (IMO) recognized the problem of invasive species invasion and adopted the "International Convention for the Control and Management of Ships' Ballast Water and Sediments" in 2004, which came into force on September 8, 2017. In 2011, the IMO approved the "Guidelines for the Control and Management of Ships' Biofouling to Minimize the Transfer of Invasive Aquatic Species" to minimize the movement of invasive species by hull-attached organisms and required ships to manage the organisms attached to their hulls. Invasive species enter new environments through ships' ballast water and hull attachment. However, several obstacles to implementing these guidelines have been identified, including a lack of underwater cleaning equipment, regulations on underwater cleaning activities in ports, and difficulty accessing crevices in underwater areas. The shipping industry, which is the party responsible for understanding these guidelines, wants to implement them for fuel cost savings resulting from the removal of organisms attached to the hull, but they anticipate significant difficulties in implementing the guidelines due to the obstacles mentioned above. Robots or people remove the organisms attached to the hull underwater, and the resulting wastewater includes various species of organisms and particles of paint and other pollutants. Currently, there is no technology available to sterilize the organisms in the wastewater or stabilize the heavy metals in the paint particles. In this study, we aim to analyze the characteristics of the wastewater generated from the removal of hull-attached organisms and select the optimal treatment technology. The organisms in the wastewater generated from the removal of the attached organisms meet the biological treatment standard (D-2) using the sterilization technology applied in the ships' ballast water treatment system. The heavy metals and other pollutants in the paint particles generated during removal are treated using stabilization technologies such as thermal decomposition. The wastewater generated is treated using a two-step process: 1) development of sterilization technology through pretreatment filtration equipment and electrolytic sterilization treatment and 2) development of technology for removing particle pollutants such as heavy metals and dissolved inorganic substances. Through this study, we will develop a biological removal technology and an environmentally friendly processing system for the waste generated after removal that meets the requirements of the government and the shipping industry and lays the groundwork for future treatment standards.Keywords: biofouling, ballast water treatment system, filtration, sterilization, wastewater
Procedia PDF Downloads 109455 Polypyrrole as Bifunctional Materials for Advanced Li-S Batteries
Authors: Fang Li, Jiazhao Wang, Jianmin Ma
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The practical application of Li-S batteries is hampered due to poor cycling stability caused by electrolyte-dissolved lithium polysulfides. Dual functionalities such as strong chemical adsorption stability and high conductivity are highly desired for an ideal host material for a sulfur-based cathode. Polypyrrole (PPy), as a conductive polymer, was widely studied as matrixes for sulfur cathode due to its high conductivity and strong chemical interaction with soluble polysulfides. Thus, a novel cathode structure consisting of a free-standing sulfur-polypyrrole cathode and a polypyrrole coated separator was designed for flexible Li-S batteries. The PPy materials show strong interaction with dissoluble polysulfides, which could suppress the shuttle effect and improve the cycling stability. In addition, the synthesized PPy film with a rough surface acts as a current collector, which improves the adhesion of sulfur materials and restrain the volume expansion, enhancing the structural stability during the cycling process. For further enhancing the cycling stability, a PPy coated separator was also applied, which could make polysulfides into the cathode side to alleviate the shuttle effect. Moreover, the PPy layer coated on commercial separator is much lighter than other reported interlayers. A soft-packaged flexible Li-S battery has been designed and fabricated for testing the practical application of the designed cathode and separator, which could power a device consisting of 24 light-emitting diode (LED) lights. Moreover, the soft-packaged flexible battery can still show relatively stable cycling performance after repeated bending, indicating the potential application in flexible batteries. A novel vapor phase deposition method was also applied to prepare uniform polypyrrole layer coated sulfur/graphene aerogel composite. The polypyrrole layer simultaneously acts as host and adsorbent for efficient suppression of polysulfides dissolution through strong chemical interaction. The density functional theory (DFT) calculations reveal that the polypyrrole could trap lithium polysulfides through stronger bonding energy. In addition, the deflation of sulfur/graphene hydrogel during the vapor phase deposition process enhances the contact of sulfur with matrixes, resulting in high sulfur utilization and good rate capability. As a result, the synthesized polypyrrole coated sulfur/graphene aerogel composite delivers a specific discharge capacity of 1167 mAh g⁻¹ and 409.1 mAh g⁻¹ at 0.2 C and 5 C respectively. The capacity can maintain at 698 mAh g⁻¹ at 0.5 C after 500 cycles, showing an ultra-slow decay rate of 0.03% per cycle.Keywords: polypyrrole, strong chemical interaction, long-term stability, Li-S batteries
Procedia PDF Downloads 140454 Pulmonary Disease Identification Using Machine Learning and Deep Learning Techniques
Authors: Chandu Rathnayake, Isuri Anuradha
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Early detection and accurate diagnosis of lung diseases play a crucial role in improving patient prognosis. However, conventional diagnostic methods heavily rely on subjective symptom assessments and medical imaging, often causing delays in diagnosis and treatment. To overcome this challenge, we propose a novel lung disease prediction system that integrates patient symptoms and X-ray images to provide a comprehensive and reliable diagnosis.In this project, develop a mobile application specifically designed for detecting lung diseases. Our application leverages both patient symptoms and X-ray images to facilitate diagnosis. By combining these two sources of information, our application delivers a more accurate and comprehensive assessment of the patient's condition, minimizing the risk of misdiagnosis. Our primary aim is to create a user-friendly and accessible tool, particularly important given the current circumstances where many patients face limitations in visiting healthcare facilities. To achieve this, we employ several state-of-the-art algorithms. Firstly, the Decision Tree algorithm is utilized for efficient symptom-based classification. It analyzes patient symptoms and creates a tree-like model to predict the presence of specific lung diseases. Secondly, we employ the Random Forest algorithm, which enhances predictive power by aggregating multiple decision trees. This ensemble technique improves the accuracy and robustness of the diagnosis. Furthermore, we incorporate a deep learning model using Convolutional Neural Network (CNN) with the RestNet50 pre-trained model. CNNs are well-suited for image analysis and feature extraction. By training CNN on a large dataset of X-ray images, it learns to identify patterns and features indicative of lung diseases. The RestNet50 architecture, known for its excellent performance in image recognition tasks, enhances the efficiency and accuracy of our deep learning model. By combining the outputs of the decision tree-based algorithms and the deep learning model, our mobile application generates a comprehensive lung disease prediction. The application provides users with an intuitive interface to input their symptoms and upload X-ray images for analysis. The prediction generated by the system offers valuable insights into the likelihood of various lung diseases, enabling individuals to take appropriate actions and seek timely medical attention. Our proposed mobile application has significant potential to address the rising prevalence of lung diseases, particularly among young individuals with smoking addictions. By providing a quick and user-friendly approach to assessing lung health, our application empowers individuals to monitor their well-being conveniently. This solution also offers immense value in the context of limited access to healthcare facilities, enabling timely detection and intervention. In conclusion, our research presents a comprehensive lung disease prediction system that combines patient symptoms and X-ray images using advanced algorithms. By developing a mobile application, we provide an accessible tool for individuals to assess their lung health conveniently. This solution has the potential to make a significant impact on the early detection and management of lung diseases, benefiting both patients and healthcare providers.Keywords: CNN, random forest, decision tree, machine learning, deep learning
Procedia PDF Downloads 73453 Spray Nebulisation Drying: Alternative Method to Produce Microparticulated Proteins
Authors: Josef Drahorad, Milos Beran, Ondrej Vltavsky, Marian Urban, Martin Fronek, Jiri Sova
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Engineering efforts of researchers of the Food research institute Prague and the Czech Technical University in spray drying technologies led to the introduction of a demonstrator ATOMIZER and a new technology of Carbon Dioxide-Assisted Spray Nebulization Drying (CASND). The equipment combines the spray drying technology, when the liquid to be dried is atomized by a rotary atomizer, with Carbon Dioxide Assisted Nebulization - Bubble Dryer (CAN-BD) process in an original way. A solution, emulsion or suspension is saturated by carbon dioxide at pressure up to 80 bar before the drying process. The atomization process takes place in two steps. In the first step, primary droplets are produced at the outlet of the rotary atomizer of special construction. In the second step, the primary droplets are divided in secondary droplets by the CO2 expansion from the inside of primary droplets. The secondary droplets, usually in the form of microbubbles, are rapidly dried by warm air stream at temperatures up to 60ºC and solid particles are formed in a drying chamber. Powder particles are separated from the drying air stream in a high efficiency fine powder separator. The product is frequently in the form of submicron hollow spheres. The CASND technology has been used to produce microparticulated protein concentrates for human nutrition from alternative plant sources - hemp and canola seed filtration cakes. Alkali extraction was used to extract the proteins from the filtration cakes. The protein solutions after the alkali extractions were dried with the demonstrator ATOMIZER. Aerosol particle size distribution and concentration in the draying chamber were determined by two different on-line aerosol spectrometers SMPS (Scanning Mobility Particle Sizer) and APS (Aerodynamic Particle Sizer). The protein powders were in form of hollow spheres with average particle diameter about 600 nm. The particles were characterized by the SEM method. The functional properties of the microparticulated protein concentrates were compared with the same protein concentrates dried by the conventional spray drying process. Microparticulated protein has been proven to have improved foaming and emulsifying properties, water and oil absorption capacities and formed long-term stable water dispersions. This work was supported by the research grants TH03010019 of the Technology Agency of the Czech Republic.Keywords: carbon dioxide-assisted spray nebulization drying, canola seed, hemp seed, microparticulated proteins
Procedia PDF Downloads 166452 Modeling Competition Between Subpopulations with Variable DNA Content in Resource-Limited Microenvironments
Authors: Parag Katira, Frederika Rentzeperis, Zuzanna Nowicka, Giada Fiandaca, Thomas Veith, Jack Farinhas, Noemi Andor
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Resource limitations shape the outcome of competitions between genetically heterogeneous pre-malignant cells. One example of such heterogeneity is in the ploidy (DNA content) of pre-malignant cells. A whole-genome duplication (WGD) transforms a diploid cell into a tetraploid one and has been detected in 28-56% of human cancers. If a tetraploid subclone expands, it consistently does so early in tumor evolution, when cell density is still low, and competition for nutrients is comparatively weak – an observation confirmed for several tumor types. WGD+ cells need more resources to synthesize increasing amounts of DNA, RNA, and proteins. To quantify resource limitations and how they relate to ploidy, we performed a PAN cancer analysis of WGD, PET/CT, and MRI scans. Segmentation of >20 different organs from >900 PET/CT scans were performed with MOOSE. We observed a strong correlation between organ-wide population-average estimates of Oxygen and the average ploidy of cancers growing in the respective organ (Pearson R = 0.66; P= 0.001). In-vitro experiments using near-diploid and near-tetraploid lineages derived from a breast cancer cell line supported the hypothesis that DNA content influences Glucose- and Oxygen-dependent proliferation-, death- and migration rates. To model how subpopulations with variable DNA content compete in the resource-limited environment of the human brain, we developed a stochastic state-space model of the brain (S3MB). The model discretizes the brain into voxels, whereby the state of each voxel is defined by 8+ variables that are updated over time: stiffness, Oxygen, phosphate, glucose, vasculature, dead cells, migrating cells and proliferating cells of various DNA content, and treat conditions such as radiotherapy and chemotherapy. Well-established Fokker-Planck partial differential equations govern the distribution of resources and cells across voxels. We applied S3MB on sequencing and imaging data obtained from a primary GBM patient. We performed whole genome sequencing (WGS) of four surgical specimens collected during the 1ˢᵗ and 2ⁿᵈ surgeries of the GBM and used HATCHET to quantify its clonal composition and how it changes between the two surgeries. HATCHET identified two aneuploid subpopulations of ploidy 1.98 and 2.29, respectively. The low-ploidy clone was dominant at the time of the first surgery and became even more dominant upon recurrence. MRI images were available before and after each surgery and registered to MNI space. The S3MB domain was initiated from 4mm³ voxels of the MNI space. T1 post and T2 flair scan acquired after the 1ˢᵗ surgery informed tumor cell densities per voxel. Magnetic Resonance Elastography scans and PET/CT scans informed stiffness and Glucose access per voxel. We performed a parameter search to recapitulate the GBM’s tumor cell density and ploidy composition before the 2ⁿᵈ surgery. Results suggest that the high-ploidy subpopulation had a higher Glucose-dependent proliferation rate (0.70 vs. 0.49), but a lower Glucose-dependent death rate (0.47 vs. 1.42). These differences resulted in spatial differences in the distribution of the two subpopulations. Our results contribute to a better understanding of how genomics and microenvironments interact to shape cell fate decisions and could help pave the way to therapeutic strategies that mimic prognostically favorable environments.Keywords: tumor evolution, intra-tumor heterogeneity, whole-genome doubling, mathematical modeling
Procedia PDF Downloads 72451 Determination of Activation Energy for Thermal Decomposition of Selected Soft Tissues Components
Authors: M. Ekiert, T. Uhl, A. Mlyniec
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Tendons are the biological soft tissue structures composed of collagen, proteoglycan, glycoproteins, water and cells of extracellular matrix (ECM). Tendons, which primary function is to transfer force generated by the muscles to the bones causing joints movement, are exposed to many micro and macro damages. In fact, tendons and ligaments trauma are one of the most numerous injuries of human musculoskeletal system, causing for many people (particularly for athletes and physically active people), recurring disorders, chronic pain or even inability of movement. The number of tendons reconstruction and transplantation procedures is increasing every year. Therefore, studies on soft tissues storage conditions (influencing i.e. tissue aging) seem to be an extremely important issue. In this study, an atomic-scale investigation on the kinetics of decomposition of two selected tendon components – collagen type I (which forms a 60-85% of a tendon dry mass) and elastin protein (which combine with ECM creates elastic fibers of connective tissues) is presented. A molecular model of collagen and elastin was developed based on crystal structure of triple-helical collagen-like 1QSU peptide and P15502 human elastin protein, respectively. Each model employed 4 linear strands collagen/elastin strands per unit cell, distributed in 2x2 matrix arrangement, placed in simulation box filled with water molecules. A decomposition phenomena was simulated with molecular dynamics (MD) method using ReaxFF force field and periodic boundary conditions. A set of NVT-MD runs was performed for 1000K temperature range in order to obtained temperature-depended rate of production of decomposition by-products. Based on calculated reaction rates activation energies and pre-exponential factors, required to formulate Arrhenius equations describing kinetics of decomposition of tested soft tissue components, were calculated. Moreover, by adjusting a model developed for collagen, system scalability and correct implementation of the periodic boundary conditions were evaluated. An obtained results provide a deeper insight into decomposition of selected tendon components. A developed methodology may also be easily transferred to other connective tissue elements and therefore might be used for further studies on soft tissues aging.Keywords: decomposition, molecular dynamics, soft tissue, tendons
Procedia PDF Downloads 210450 Poly(ε-caprolactone)/Halloysite Nanotube Nanocomposites Scaffolds for Tissue Engineering
Authors: Z. Terzopoulou, I. Koliakou, D. Bikiaris
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Tissue engineering offers a new approach to regenerate diseased or damaged tissues such as bone. Great effort is devoted to eliminating the need of removing non-degradable implants at the end of their life span, with biodegradable polymers playing a major part. Poly(ε-caprolactone) (PCL) is one of the best candidates for this purpose due to its high permeability, good biodegradability and exceptional biocompatibility, which has stimulated extensive research into its potential application in the biomedical fields. However, PCL degrades much slower than other known biodegradable polymers and has a total degradation of 2-4 years depending on the initial molecular weight of the device. This is due to its relatively hydrophobic character and high crystallinity. Consequently, much attention has been given to the tunable degradation of PCL to meet the diverse requirements of biomedicine. Poly(ε-caprolactone) (PCL) is a biodegradable polyester that lacks bioactivity, so when used in bone tissue engineering, new bone tissue cannot bond tightly on the polymeric surface. Therefore, it is important to incorporate reinforcing fillers into PCL matrix in order to result in a promising combination of bioactivity, biodegradability, and strength. Natural clay halloysite nanotubes (HNTs) were incorporated into PCL polymeric matrix, via in situ ring-opening polymerization of caprolactone, in concentrations 0.5, 1 and 2.5 wt%. Both unmodified and modified with aminopropyltrimethoxysilane (APTES) HNTs were used in this study. The effect of nanofiller concentration and functionalization with end-amino groups on the physicochemical properties of the prepared nanocomposites was studied. Mechanical properties were found enhanced after the incorporation of nanofillers, while the modification increased further the values of tensile and impact strength. Thermal stability of PCL was not affected by the presence of nanofillers, while the crystallization rate that was studied by Differential Scanning Calorimetry (DSC) and Polarized Light Optical Microscopy (POM) increased. All materials were subjected to enzymatic hydrolysis in phosphate buffer in the presence of lipases. Due to the hydrophilic nature of HNTs, the biodegradation rate of nanocomposites was higher compared to neat PCL. In order to confirm the effect of hydrophilicity, contact angle measurements were also performed. In vitro biomineralization test confirmed that all samples were bioactive as mineral deposits were detected by X-ray diffractometry after incubation in SBF. All scaffolds were tested in relevant cell culture using osteoblast-like cells (MG-63) to demonstrate their biocompatibilityKeywords: biomaterials, nanocomposites, scaffolds, tissue engineering
Procedia PDF Downloads 316449 Towards a Strategic Framework for State-Level Epistemological Functions
Authors: Mark Darius Juszczak
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While epistemology, as a sub-field of philosophy, is generally concerned with theoretical questions about the nature of knowledge, the explosion in digital media technologies has resulted in an exponential increase in the storage and transmission of human information. That increase has resulted in a particular non-linear dynamic – digital epistemological functions are radically altering how and what we know. Neither the rate of that change nor the consequences of it have been well studied or taken into account in developing state-level strategies for epistemological functions. At the current time, US Federal policy, like that of virtually all other countries, maintains, at the national state level, clearly defined boundaries between various epistemological agencies - agencies that, in one way or another, mediate the functional use of knowledge. These agencies can take the form of patent and trademark offices, national library and archive systems, departments of education, departments such as the FTC, university systems and regulations, military research systems such as DARPA, federal scientific research agencies, medical and pharmaceutical accreditation agencies, federal funding for scientific research and legislative committees and subcommittees that attempt to alter the laws that govern epistemological functions. All of these agencies are in the constant process of creating, analyzing, and regulating knowledge. Those processes are, at the most general level, epistemological functions – they act upon and define what knowledge is. At the same time, however, there are no high-level strategic epistemological directives or frameworks that define those functions. The only time in US history where a proxy state-level epistemological strategy existed was between 1961 and 1969 when the Kennedy Administration committed the United States to the Apollo program. While that program had a singular technical objective as its outcome, that objective was so technologically advanced for its day and so complex so that it required a massive redirection of state-level epistemological functions – in essence, a broad and diverse set of state-level agencies suddenly found themselves working together towards a common epistemological goal. This paper does not call for a repeat of the Apollo program. Rather, its purpose is to investigate the minimum structural requirements for a national state-level epistemological strategy in the United States. In addition, this paper also seeks to analyze how the epistemological work of the multitude of national agencies within the United States would be affected by such a high-level framework. This paper is an exploratory study of this type of framework. The primary hypothesis of the author is that such a function is possible but would require extensive re-framing and reclassification of traditional epistemological functions at the respective agency level. In much the same way that, for example, DHS (Department of Homeland Security) evolved to respond to a new type of security threat in the world for the United States, it is theorized that a lack of coordination and alignment in epistemological functions will equally result in a strategic threat to the United States.Keywords: strategic security, epistemological functions, epistemological agencies, Apollo program
Procedia PDF Downloads 77448 Interlayer-Mechanical Working: Effective Strategy to Mitigate Solidification Cracking in Wire-Arc Additive Manufacturing (WAAM) of Fe-based Shape Memory Alloy
Authors: Soumyajit Koley, Kuladeep Rajamudili, Supriyo Ganguly
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In recent years, iron-based shape-memory alloys have been emerging as an inexpensive alternative to costly Ni-Ti alloy and thus considered suitable for many different applications in civil structures. Fe-17Mn-10Cr-5Si-4Ni-0.5V-0.5C alloy contains 37 wt.% of total solute elements. Such complex multi-component metallurgical system often leads to severe solute segregation and solidification cracking. Wire-arc additive manufacturing (WAAM) of Fe-17Mn-10Cr-5Si-4Ni-0.5V-0.5C alloy was attempted using a cold-wire fed plasma arc torch attached to a 6-axis robot. Self-standing walls were manufactured. However, multiple vertical cracks were observed after deposition of around 15 layers. Microstructural characterization revealed open surfaces of dendrites inside the crack, confirming these cracks as solidification cracks. Machine hammer peening (MHP) process was adopted on each layer to cold work the newly deposited alloy. Effect of MHP traverse speed were varied systematically to attain a window of operation where cracking was completely stopped. Microstructural and textural analysis were carried out further to correlate the peening process to microstructure.MHP helped in many ways. Firstly, a compressive residual stress was induced on each layer which countered the tensile residual stress evolved from solidification process; thus, reducing net tensile stress on the wall along its length. Secondly, significant local plastic deformation from MHP followed by the thermal cycle induced by deposition of next layer resulted into a recovered and recrystallized equiaxed microstructure instead of long columnar grains along the vertical direction. This microstructural change increased the total crack propagation length and thus, the overall toughness. Thirdly, the inter-layer peening significantly reduced the strong cubic {001} crystallographic texture formed along the build direction. Cubic {001} texture promotes easy separation of planes and easy crack propagation. Thus reduction of cubic texture alleviates the chance of cracking.Keywords: Iron-based shape-memory alloy, wire-arc additive manufacturing, solidification cracking, inter-layer cold working, machine hammer peening
Procedia PDF Downloads 72447 Laser Paint Stripping on Large Zones on AA 2024 Based Substrates
Authors: Selen Unaldi, Emmanuel Richaud, Matthieu Gervais, Laurent Berthe
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Aircrafts are painted with several layers to guarantee their protection from external attacks. For aluminum AA 2024-T3 (metallic structural part of the plane), a protective primer is applied to ensure its corrosion protection. On top of this layer, the top coat is applied for aesthetic aspects. During the lifetime of an aircraft, top coat stripping has an essential role which should be operated as an average of every four years. However, since conventional stripping processes create hazardous disposals and need long hours of labor work, alternative methods have been investigated. Amongst them, laser stripping appears as one of the most promising techniques not only because of the reasons mentioned above but also its controllable and monitorable aspects. The application of a laser beam from the coated side provides stripping, but the depth of the process should be well controlled in order to prevent damage to a substrate and the anticorrosion primer. Apart from that, thermal effects should be taken into account on the painted layers. As an alternative, we worked on developing a process that includes the usage of shock wave propagation to create the stripping via mechanical effects with the application of the beam from the substrate side (back face) of the samples. Laser stripping was applied on thickness-specified samples with a thickness deviation of 10-20%. First, the stripping threshold is determined as a function of power density which is the first flight off of the top coats. After obtaining threshold values, the same power densities were applied to specimens to create large stripping zones with a spot overlap of 10-40%. Layer characteristics were determined on specimens in terms of physicochemical properties and thickness range both before and after laser stripping in order to validate the substrate material health and coating properties. The substrate health is monitored by measuring the roughness of the laser-impacted zones and free surface energy tests (both before and after laser stripping). Also, Hugoniot Elastic Limit (HEL) is determined from VISAR diagnostic on AA 2024-T3 substrates (for the back face surface deformations). In addition, the coating properties are investigated as a function of adhesion levels and anticorrosion properties (neutral salt spray test). The influence of polyurethane top-coat thickness is studied in order to verify the laser stripping process window for industrial aircraft applications.Keywords: aircraft coatings, laser stripping, laser adhesion tests, epoxy, polyurethane
Procedia PDF Downloads 78446 Precocious Puberty Due to an Autonomous Ovarian Cyst in a 3-Year-Old Girl: Case Report
Authors: Aleksandra Chałupnik, Zuzanna Chilimoniuk, Joanna Borowik, Aleksandra Borkowska, Anna Torres
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Background: Precocious puberty is the occurrence of secondary sexual characteristics in girls before the age of 8. The diverse etiology of premature puberty is crucial to determine whether it is true precocious puberty, depending on the activation of the hypothalamic-pituitary-gonadal axis, or pseudo-precocious, which is independent of the activation of this axis. Whatever the cause, premature action of the sex hormones leads to the common symptoms of various forms of puberty. These include the development of sexual characteristics, acne, acceleration of growth rate and acceleration of skeletal maturation. Due to the possible genetic basis of the disorders, an interdisciplinary search for the cause is needed. Case report: The case report concerns a patient of a pediatric gynecology clinic who, at the age of two years, developed advanced thelarhe (M3) and started recurrent vaginal bleeding. In August 2019, gonadotropin suppression initially and after LHRH stimulation and high estradiol levels were reported at the Endocrinology Department. Imaging examinations showed a cyst in the right ovary projection. The bone age was six years. The entire clinical picture indicated pseudo- (peripheral) precocious in the course of ovarian autonomic cyst. In the follow-up ultrasound performed in September, the image of the cyst was stationary and normalization of estradiol levels and clinical symptoms was noted. In December 2019, cyst regression and normal gonadotropin and estradiol concentrations were found. In June 2020, white mucus tinged with blood on the underwear, without any other disturbing symptoms, was observed for several days. Two consecutive USG examinations carried out in the same month confirmed the change in the right ovary, the diameter of which was 25 mm with a very high level of estradiol. Germinal tumor markers were normal. On the Tanner scale, the patient scored M2P1. The labia and hymen had puberty features. The correct vaginal entrance was visible. Another active vaginal bleeding occurred in the first week of July 2020. The considered laparoscopic treatment was abandoned due to the lack of oncological indications. Treatment with Tamoxifen was recommended in July 2020. In the initiating period of treatment, no maturation progression, and even reduction of symptoms, no acceleration of growth and a marked reduction in the size of the cysts were noted. There was no bleeding. After the size of the cyst and hormonal activity increased again, the treatment was changed to Anastrozole, the effect of which led to a reduction in the size of the cyst. Conclusions: The entire clinical picture indicates alleged (peripheral) puberty. Premature puberty in girls, which is manifested as enlarged mammary glands with high levels of estrogens secreted by autonomic ovarian cysts and prepubertal levels of gonadotropins, may indicate McCune-Albright syndrome. Vaginal bleeding may also occur in this syndrome. Cancellation of surgical treatment of the cyst made it impossible to perform a molecular test that would allow to confirm the diagnosis. Taking into account the fact that cysts are often one of the first symptoms of McCune-Albrigt syndrome, it is important to remember about multidisciplinary care for the patient and careful search for skin and bone changes or other hormonal disorders.Keywords: McCune Albrigth's syndrome, ovarian cyst, pediatric gynaecology, precocious puberty
Procedia PDF Downloads 190445 Environment Patterns and Mental Health of Older Adults in Long-Term Care Facilities: The Role of Activity Profiles
Authors: Shiau-Fang Chao, Yu-Chih Chen
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Owing to physical limitations and restrained lifestyle, older long-term care (LTC) residents are more likely to be affected by their environment than their community-dwelling counterparts. They also participate fewer activities and experience worse mental health than healthy older adults. This study adopts the ICF model to determine the extent to which the clustered patterns of LTC environment and activity participation are associated with older residents’ mental health. Method: Data were collected from a stratified equal probability sample of 634 older residents in 155 LTC institutions in Taiwan. Latent profile analysis (LPA) and latent class analysis (LCA) were conducted to explore the profiles for environment and activity participation. Multilevel modeling was performed to elucidate the relationships among environment profiles, activity profiles, and mental health. Results: LPA identified three mutually exclusive environment profiles (Low-, Moderate-, and High-Support Environment) based on the physical, social, and attitudinal environmental domains, consolidated from 12 environmental measures. LCA constructed two distinct activity profiles (Low- and High-Activity Participation) across seven activity domains (outdoor, volunteer-led leisure, spiritual, household chores, interpersonal exchange, social, and sedentary activity) that were factored from 20 activities. Compared to the Low-Support Environment class, older adults in the Moderate- and High-Support Environment classes had better mental health. Older residents in the Moderate- and High-Support Environment classes were more likely to be in the “High Activity” class, which in turn, exhibited better mental health. Conclusion: This study advances the current knowledge through rigorous methods and study design. The study findings lead to several conclusions. First, this study supports the use of ICF framework to institutionalized older individuals with functional limitations and demonstrates that both measures of environment and activity participation can be refined from multiple indicators. Second, environmental measures that encompass the physical, social, and attitudinal domains would provide a more comprehensive assessment on the place where an older individual embeds. Third, simply counting activities in which an older individual participates or considering a certain type of activity may not capture his or her way of life. Practitioners should not only focus on group or leisure activities within the institutions; rather, more efforts should be made to consider residents’ preferences for everyday life and support their remaining ability by encouraging continuous participation in activities they still willing and capable to perform. Fourth, environment and activity participation are modifiable factors which have greater potential to strengthen older LTC residents’ mental health, and activity participation should be considered in the link between environment and mental health. A combination of enhanced physical, social, and attitudinal environments, and continual engagement in various activities may optimize older LTC residents’ mental health.Keywords: activity, environment, mental health, older LTC residents
Procedia PDF Downloads 197444 Industrial Waste Multi-Metal Ion Exchange
Authors: Thomas S. Abia II
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Intel Chandler Site has internally developed its first-of-kind (FOK) facility-scale wastewater treatment system to achieve multi-metal ion exchange. The process was carried out using a serial process train of carbon filtration, pH / ORP adjustment, and cationic exchange purification to treat dilute metal wastewater (DMW) discharged from a substrate packaging factory. Spanning a trial period of 10 months, a total of 3,271 samples were collected and statistically analyzed (average baseline + standard deviation) to evaluate the performance of a 95-gpm, multi-reactor continuous copper ion exchange treatment system that was consequently retrofitted for manganese ion exchange to meet environmental regulations. The system is also equipped with an inline acid and hot caustic regeneration system to rejuvenate exhausted IX resins and occasionally remove surface crud. Data generated from lab-scale studies was transferred to system operating modifications following multiple trial-and-error experiments. Despite the DMW treatment system failing to meet internal performance specifications for manganese output, it was observed to remove the cation notwithstanding the prevalence of copper in the waste stream. Accordingly, the average manganese output declined from 6.5 + 5.6 mg¹L⁻¹ at pre-pilot to 1.1 + 1.2 mg¹L⁻¹ post-pilot (83% baseline reduction). This milestone was achieved regardless of the average influent manganese to DMW increasing from 1.0 + 13.7 mg¹L⁻¹ at pre-pilot to 2.1 + 0.2 mg¹L⁻¹ post-pilot (110% baseline uptick). Likewise, the pre-trial and post-trial average influent copper values to DMW were 22.4 + 10.2 mg¹L⁻¹ and 32.1 + 39.1 mg¹L⁻¹, respectively (43% baseline increase). As a result, the pre-trial and post-trial average copper output values were 0.1 + 0.5 mg¹L⁻¹ and 0.4 + 1.2 mg¹L⁻¹, respectively (300% baseline uptick). Conclusively, the operating pH range upstream of treatment (between 3.5 and 5) was shown to be the largest single point of influence for optimizing manganese uptake during multi-metal ion exchange. However, the high variability of the influent copper-to-manganese ratio was observed to adversely impact the system functionality. The journal herein intends to discuss the operating parameters such as pH and oxidation-reduction potential (ORP) that were shown to influence the functional versatility of the ion exchange system significantly. The literature also proposes to discuss limitations of the treatment system such as influent copper-to-manganese ratio variations, operational configuration, waste by-product management, and system recovery requirements to provide a balanced assessment of the multi-metal ion exchange process. The take-away from this literature is intended to analyze the overall feasibility of ion exchange for metals manufacturing facilities that lack the capability to expand hardware due to real estate restrictions, aggressive schedules, or budgetary constraints.Keywords: copper, industrial wastewater treatment, multi-metal ion exchange, manganese
Procedia PDF Downloads 143443 The Investigation of Effect of Alpha Lipoic Acid against Damage on Neonatal Rat Lung to Maternal Tobacco Smoke Exposure
Authors: Elif Erdem, Nalan Kaya, Gonca Ozan, Durrin Ozlem Dabak, Enver Ozan
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This study was carried out to determine the histological and biochemical changes in the lungs of the rat pups exposed to tobacco smoke during pregnancy period and to investigate the protective effects of alpha lipoic acid, which is administered during pregnancy, on these changes. In our study, 24 six-week old Spraque-Dawley female rats weighing 160 ± 10 g were used (n:7). Rats were randomly divided into four equal groups: group I (control), group II (tobacco smoke), group III (tobacco smoke + alpha lipoic acid) and group IV (alpha lipoic acid). Rats in the group II, group III were exposed to tobacco smoke twice a day for one hour starting from eight weeks before mating and during pregnancy. In addition to tobacco smoke, 20 mg/kg of alpha lipoic acid was administered via oral gavage to the rats in the group III. Only alpha lipoic acid was administered to the rats in the group IV. Once after the delivery, all administrations were stopped. On the 7 and 21th days, the seven pups of all groups were decapitated. A portion of the lung was taken and stained with HE, PAS and Masson. In addition to immunohistochemical staining of surfactant protein A, vascular endothelial growth factor, caspase-3, TUNEL method was also used to determine apoptosis. Biochemical analyzes were performed with some part of the lung tissue specimens. In the histological evaluations performed under light microscopy, inflammatory cell increase, hemorrhagic areas, edema, interalveolar septal thickening, alveolar numbers decrease, degeneration of some bronchi and bronchial epithelium, epithelial cells that were fallen into the lumen and hyaline membrane formation were observed in tobacco smoke group. These findings were ameliorated in tobacco smoke + ALA group. Hyaline membrane formation was not detected in this group. The TUNEL positive cell numbers a significant increase was detected in the tobacco smoke group, whereas a significant decrease was detected in the tobacco smoke + ALA group. In terms of the immunoreactivity of both SP-A and VEGF, a significant decrease was observed in the tobacco smoke group, and a significant increase was observed in the tobacco smoke + ALA group. Regarding the immunoreactivity of caspase-3, there was a significant increase in the group of tobacco smoke and a significant decrease in the group of tobacco smoke + ALA. The malondialdehyde levels were determined to be significantly increased in the tobacco smoke group, and a significant decreased in the tobacco smoke + ALA. Glutathione and superoxide dismutase enzyme activities showed a significant decrease in the group of tobacco smoke and a significant increase in the tobacco smoke + ALA group. In conclusion, we suggest that the exposure to tobacco smoke during pregnancy leads to morphological, histopathological and functional changes on lung development by causing oxidative damage in lung tissues of neonatal rats and the maternal use of alpha lipoic acid can provide a protective effect on the neonatal lung development against this oxidative stress originating from tobacco smoke.Keywords: alpha lipoic acid, lung, neonate, tobacco smoke, pregnancy
Procedia PDF Downloads 211442 Optical Assessment of Marginal Sealing Performance around Restorations Using Swept-Source Optical Coherence Tomography
Authors: Rima Zakzouk, Yasushi Shimada, Yasunori Sumi, Junji Tagami
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Background and purpose: The resin composite has become the main material for the restorations of caries in recent years due to aesthetic characteristics, especially with the development of the adhesive techniques. The quality of adhesion to tooth structures is depending on an exchange process between inorganic tooth material and synthetic resin and a micromechanical retention promoted by resin infiltration in partially demineralized dentin. Optical coherence tomography (OCT) is a noninvasive diagnostic method for obtaining cross-sectional images that produce high-resolution of the biological tissue at the micron scale. The aim of this study was to evaluate the gap formation at adhesive/tooth interface of two-step self-etch adhesives that are preceded with or without phosphoric acid pre-etching in different regions of teeth using SS-OCT. Materials and methods: Round tapered cavities (2×2 mm) were prepared in cervical part of bovine incisors teeth and divided into 2 groups (n=10): first group self-etch adhesive (Clearfil SE Bond) was applied for SE group and second group treated with acid etching before applying the self-etch adhesive for PA group. Subsequently, both groups were restored with Estelite Flow Quick Flowable Composite Resin and observed under OCT. Following 5000 thermal cycles, the same section was obtained again for each cavity using OCT at 1310-nm wavelength. Scanning was repeated after two months to monitor the gap progress. Then the gap length was measured using image analysis software, and the statistics analysis were done between both groups using SPSS software. After that, the cavities were sectioned and observed under Confocal Laser Scanning Microscope (CLSM) to confirm the result of OCT. Results: Gaps formed at the bottom of the cavity was longer than the gap formed at the margin and dento-enamel junction in both groups. On the other hand, pre-etching treatment led to damage the DEJ regions creating longer gap. After 2 months the results showed almost progress in the gap length significantly at the bottom regions in both groups. In conclusions, phosphoric acid etching treatment did not reduce the gap lrngth in most regions of the cavity. Significance: The bottom region of tooth was more exposed to gap formation than margin and DEJ regions, The DEJ damaged with phosphoric acid treatment.Keywords: optical coherence tomography, self-etch adhesives, bottom, dento enamel junction
Procedia PDF Downloads 226441 Stable Time Reversed Integration of the Navier-Stokes Equation Using an Adjoint Gradient Method
Authors: Jurriaan Gillissen
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This work is concerned with stabilizing the numerical integration of the Navier-Stokes equation (NSE), backwards in time. Applications involve the detection of sources of, e.g., sound, heat, and pollutants. Stable reverse numerical integration of parabolic differential equations is also relevant for image de-blurring. While the literature addresses the reverse integration problem of the advection-diffusion equation, the problem of numerical reverse integration of the NSE has, to our knowledge, not yet been addressed. Owing to the presence of viscosity, the NSE is irreversible, i.e., when going backwards in time, the fluid behaves, as if it had a negative viscosity. As an effect, perturbations from the perfect solution, due to round off errors or discretization errors, grow exponentially in time, and reverse integration of the NSE is inherently unstable, regardless of using an implicit time integration scheme. Consequently, some sort of filtering is required, in order to achieve a stable, numerical, reversed integration. The challenge is to find a filter with a minimal adverse affect on the accuracy of the reversed integration. In the present work, we explore an adjoint gradient method (AGM) to achieve this goal, and we apply this technique to two-dimensional (2D), decaying turbulence. The AGM solves for the initial velocity field u0 at t = 0, that, when integrated forward in time, produces a final velocity field u1 at t = 1, that is as close as is feasibly possible to some specified target field v1. The initial field u0 defines a minimum of a cost-functional J, that measures the distance between u1 and v1. In the minimization procedure, the u0 is updated iteratively along the gradient of J w.r.t. u0, where the gradient is obtained by transporting J backwards in time from t = 1 to t = 0, using the adjoint NSE. The AGM thus effectively replaces the backward integration by multiple forward and backward adjoint integrations. Since the viscosity is negative in the adjoint NSE, each step of the AGM is numerically stable. Nevertheless, when applied to turbulence, the AGM develops instabilities, which limit the backward integration to small times. This is due to the exponential divergence of phase space trajectories in turbulent flow, which produces a multitude of local minima in J, when the integration time is large. As an effect, the AGM may select unphysical, noisy initial conditions. In order to improve this situation, we propose two remedies. First, we replace the integration by a sequence of smaller integrations, i.e., we divide the integration time into segments, where in each segment the target field v1 is taken as the initial field u0 from the previous segment. Second, we add an additional term (regularizer) to J, which is proportional to a high-order Laplacian of u0, and which dampens the gradients of u0. We show that suitable values for the segment size and for the regularizer, allow a stable reverse integration of 2D decaying turbulence, with accurate results for more then O(10) turbulent, integral time scales.Keywords: time reversed integration, parabolic differential equations, adjoint gradient method, two dimensional turbulence
Procedia PDF Downloads 224440 Clinical Efficacy of Localized Salvage Prostate Cancer Reirradiation with Proton Scanning Beam Therapy
Authors: Charles Shang, Salina Ramirez, Stephen Shang, Maria Estrada, Timothy R. Williams
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Purpose: Over the past decade, proton therapy utilizing pencil beam scanning has emerged as a preferred treatment modality in radiation oncology, particularly for prostate cancer. This retrospective study aims to assess the clinical and radiobiological efficacy of proton scanning beam therapy in the treatment of localized salvage prostate cancer, following initial radiation therapy with a different modality. Despite the previously delivered high radiation doses, this investigation explores the potential of proton reirradiation in controlling recurrent prostate cancer and detrimental quality of life side effects. Methods and Materials: A retrospective analysis was conducted on 45 cases of locally recurrent prostate cancer that underwent salvage proton reirradiation. Patients were followed for 24.6 ± 13.1 months post-treatment. These patients had experienced an average remission of 8.5 ± 7.9 years after definitive radiotherapy for localized prostate cancer (n=41) or post-prostatectomy (n=4), followed by rising PSA levels. Recurrent disease was confirmed by FDG-PET (n=31), PSMA-PET (n=10), or positive local biopsy (n=4). Gross tumor volume (GTV) was delineated based on PET and MR imaging, with the planning target volume (PTV) expanding to an average of 10.9 cm³. Patients received proton reirradiation using two oblique coplanar beams, delivering total doses ranging from 30.06 to 60.00 GyE in 17–30 fractions. All treatments were administered using the ProBeam Compact system with CT image guidance. The International Prostate Symptom Scores (IPSS) and prostate-specific antigen (PSA) levels were evaluated to assess treatment-related toxicity and tumor control. Results and Discussions: In this cohort (mean age: 76.7 ± 7.3 years), 60% (27/45) of patients showed sustained reductions in PSA levels post-treatment, while 36% (16/45) experienced a PSA decline of more than 0.8 ng/mL. Additionally, 73% (33/45) of patients exhibited an initial PSA reduction, though some showed later PSA increases, indicating the potential presence of undetected metastatic lesions. The median post-retreatment IPSS score was 4, significantly lower than scores reported in other treatment studies. Overall, 69% of patients reported mild urinary symptoms, with 96% (43/45) experiencing mild to moderate symptoms. Three patients experienced grade I or II proctitis, while one patient reported grade III proctitis. These findings suggest that regional organs, including the urethra, bladder, and rectum, demonstrate significant radiobiological recovery from prior radiation exposure, enabling tolerance to additional proton scanning beam therapy. Conclusions: This retrospective analysis of 45 patients with recurrent localized prostate cancer treated with salvage proton reirradiation demonstrates favorable outcomes, with a median follow-up of two years. The post-retreatment IPSS scores were comparable to those reported in follow-up studies of initial radiation therapy treatments, indicating stable or improved urinary symptoms compared to the end of initial treatment. These results highlight the efficacy of proton scanning beam therapy in providing effective salvage treatment while minimizing adverse effects on critical organs. The findings also enhance the understanding of radiobiological responses to reirradiation and support proton therapy as a viable option for patients with recurrent localized prostate cancer following previous definitive radiation therapy.Keywords: prostate salvage radiotherapy, proton therapy, biological radiation tolerance, radiobiology of organs
Procedia PDF Downloads 18439 Approach on Conceptual Design and Dimensional Synthesis of the Linear Delta Robot for Additive Manufacturing
Authors: Efrain Rodriguez, Cristhian Riano, Alberto Alvares
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In recent years, robots manipulators with parallel architectures are used in additive manufacturing processes – 3D printing. These robots have advantages such as speed and lightness that make them suitable to help with the efficiency and productivity of these processes. Consequently, the interest for the development of parallel robots for additive manufacturing applications has increased. This article deals with the conceptual design and dimensional synthesis of the linear delta robot for additive manufacturing. Firstly, a methodology based on structured processes for the development of products through the phases of informational design, conceptual design and detailed design is adopted: a) In the informational design phase the Mudge diagram and the QFD matrix are used to aid a set of technical requirements, to define the form, functions and features of the robot. b) In the conceptual design phase, the functional modeling of the system through of an IDEF0 diagram is performed, and the solution principles for the requirements are formulated using a morphological matrix. This phase includes the description of the mechanical, electro-electronic and computational subsystems that constitute the general architecture of the robot. c) In the detailed design phase, a digital model of the robot is drawn on CAD software. A list of commercial and manufactured parts is detailed. Tolerances and adjustments are defined for some parts of the robot structure. The necessary manufacturing processes and tools are also listed, including: milling, turning and 3D printing. Secondly, a dimensional synthesis method applied on design of the linear delta robot is presented. One of the most important key factors in the design of a parallel robot is the useful workspace, which strongly depends on the joint space, the dimensions of the mechanism bodies and the possible interferences between these bodies. The objective function is based on the verification of the kinematic model for a prescribed cylindrical workspace, considering geometric constraints that possibly lead to singularities of the mechanism. The aim is to determine the minimum dimensional parameters of the mechanism bodies for the proposed workspace. A method based on genetic algorithms was used to solve this problem. The method uses a cloud of points with the cylindrical shape of the workspace and checks the kinematic model for each of the points within the cloud. The evolution of the population (point cloud) provides the optimal parameters for the design of the delta robot. The development process of the linear delta robot with optimal dimensions for additive manufacture is presented. The dimensional synthesis enabled to design the mechanism of the delta robot in function of the prescribed workspace. Finally, the implementation of the robotic platform developed based on a linear delta robot in an additive manufacturing application using the Fused Deposition Modeling (FDM) technique is presented.Keywords: additive manufacturing, delta parallel robot, dimensional synthesis, genetic algorithms
Procedia PDF Downloads 190438 Phytochemicals and Photosynthesis of Grape Berry Exocarp and Seed (Vitis vinifera, cv. Alvarinho): Effects of Foliar Kaolin and Irrigation
Authors: Andreia Garrido, Artur Conde, Ana Cunha, Ric De Vos
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Climate changes predictions point to increases in abiotic stress for crop plants in Portugal, like pronounced temperature variation and decreased precipitation, which will have negative impact on grapevine physiology and consequently, on grape berry and wine quality. Short-term mitigation strategies have, therefore, been implemented to alleviate the impacts caused by adverse climatic periods. These strategies include foliar application of kaolin, an inert mineral, which has radiation reflection proprieties that decreases stress from excessive heat/radiation absorbed by its leaves, as well as smart irrigation strategies to avoid water stress. However, little is known about the influence of these mitigation measures on grape berries, neither on the photosynthetic activity nor on the photosynthesis-related metabolic profiles of its various tissues. Moreover, the role of fruit photosynthesis on berry quality is poorly understood. The main objective of our work was to assess the effects of kaolin and irrigation treatments on the photosynthetic activity of grape berry tissues (exocarp and seeds) and on their global metabolic profile, also investigating their possible relationship. We therefore collected berries of field-grown plants of the white grape variety Alvarinho from two distinct microclimates, i.e. from clusters exposed to high light (HL, 150 µmol photons m⁻² s⁻¹) and low light (LL, 50 µmol photons m⁻² s⁻¹), from both kaolin and non-kaolin (control) treated plants at three fruit developmental stages (green, véraison and mature). Plant irrigation was applied after harvesting the green berries, which also enabled comparison of véraison and mature berries from irrigated and non-irrigated growth conditions. Photosynthesis was assessed by pulse amplitude modulated chlorophyll fluorescence imaging analysis, and the metabolite profile of both tissues was assessed by complementary metabolomics approaches. Foliar kaolin application resulted in, for instance, an increased photosynthetic activity of the exocarp of LL-grown berries at green developmental stage, as compared to the control non-kaolin treatment, with a concomitant increase in the levels of several lipid-soluble isoprenoids (chlorophylls, carotenoids, and tocopherols). The exocarp of mature berries grown at HL microclimate on kaolin-sprayed non-irrigated plants had higher total sugar levels content than all other treatments, suggesting that foliar application of this mineral results in an increased accumulation of photoassimilates in mature berries. Unbiased liquid chromatography-mass spectrometry-based profiling of semi-polar compounds followed by ASCA (ANOVA simultaneous component analysis) and ANOVA statistical analysis indicated that kaolin had no or inconsistent effect on the flavonoid and phenylpropanoid composition in both seed and exocarp at any developmental stage; in contrast, both microclimate and irrigation influenced the level of several of these compounds depending on berry ripening stage. Overall, our study provides more insight into the effects of mitigation strategies on berry tissue photosynthesis and phytochemistry, under contrasting conditions of cluster light microclimate. We hope that this may contribute to develop sustainable management in vineyards and to maintain grape berries and wines with high quality even at increasing abiotic stress challenges.Keywords: climate change, grape berry tissues, metabolomics, mitigation strategies
Procedia PDF Downloads 123437 Investigation of Polypropylene Composite Films With Carbon Nanotubes and the Role of β Nucleating Agents for the Improvement of Their Water Vapor Permeability
Authors: Glykeria A. Visvini, George N. Mathioudakis, Amaia Soto Beobide, Aris E. Giannakas, George A. Voyiatzis
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Polymeric nanocomposites have generated considerable interest in both academic research and industry because their properties can be tailored by adjusting the type & concentration of nano-inclusions, resulting in complementary and adaptable characteristics. The exceptional and/or unique properties of the nanocomposites, including the high mechanical strength and stiffness, the ease of processing, and their lightweight nature, are attributed to the high surface area, the electrical and/or thermal conductivity of the nano-fillers, which make them appealing materials for a wide range of engineering applications. Polymeric «breathable» membranes enabling water vapor permeability (WVP) can be designed either by using micro/nano-fillers with the ability to interrupt the continuity of the polymer phase generating micro/nano-porous structures or/and by creating micro/nano-pores into the composite material by uniaxial/biaxial stretching. Among the nanofillers, carbon nanotubes (CNTs) exhibit particular high WVP and for this reason, they have already been proposed for gas separation membranes. In a similar context, they could prove to be promising alternative/complementary filler nano-materials, for the development of "breathable" products. Polypropylene (PP) is a commonly utilized thermoplastic polymer matrix in the development of composite films, due to its easy processability and low price, combined with its good chemical & physical properties. PP is known to present several crystalline phases (α, β and γ), depending on the applied treatment process, which have a significant impact on its final properties, particularly in terms of WVP. Specifically, the development of the β-phase in PP in combination with stretching is anticipated to modify the crystalline behavior and extend the microporosity of the polymer matrix exhibiting enhanced WVP. The primary objective of this study is to develop breathable nano-carbon based (functionalized MWCNTs) PP composite membranes, potentially also avoiding the stretching process. This proposed alternative is expected to have a better performance/cost ratio over current stretched PP/CaCO3 composite benchmark membranes. The focus is to investigate the impact of both β-nucleator(s) and nano-carbon fillers on water vapor transmission rate properties of relevant PP nanocomposites.Keywords: carbon nanotubes, nanocomposites, nucleating agents, polypropylene, water vapor permeability
Procedia PDF Downloads 73436 The Use of Rotigotine to Improve Hemispatial Neglect in Stroke Patients at the Charing Cross Neurorehabilitation Unit
Authors: Malab Sana Balouch, Meenakshi Nayar
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Hemispatial Neglect is a common disorder primarily associated with right hemispheric stroke, in the acute phase of which it can occur up to 82% of the time. Such individuals fail to acknowledge or respond to people and objects in their left field of vision due to deficits in attention and awareness. Persistent hemispatial neglect significantly impedes post-stroke recovery, leading to longer hospital stays post-stroke, increased functional dependency, longer-term disability in ADLs and increased risk of falls. Recently, evidence has emerged for the use of dopamine agonist Rotigotine in neglect. The aim of our Quality Improvement Project (QIP) is to evaluate and better the current protocols and practice in assessment, documentation and management of neglect and rotigotine use at the Neurorehabilitation unit at Charing Cross Hospital (CNRU). In addition, it brings light to rotigotine use in the management of hemispatial neglect and paves the way for future research in the field. Our QIP was based in the CNRU. All patients admitted to the CNRU suffering from a right-sided stroke from 2nd of February 2018 to the 2nd of February 2021 were included in the project. Each patient’s multidisciplinary team report and hospital notes were searched for information, including bio-data, fulfilment of the inclusion criteria (having hemispatial neglect) and data related to rotigotine use. This includes whether or not the drug was administered, any contraindications to drug in patients that did not receive it, and any therapeutic benefits(subjective or objective improvement in neglect) in those that did receive the rotigotine. Data was simultaneously entered into excel sheet and further statistical analysis was done on SPSS 20.0. Out of 80 patients suffering from right sided strokes, 72.5% were infarcts and 27.5% were hemorrhagic strokes, with vast majority of both types of strokes were in the middle cerebral artery territory (MCA). A total of 31 (38.8%) of our patients were noted to have hemispatial neglect, with the highest number of cases being associated with MCA strokes. Almost half of our patients with MCA strokes suffered from neglect. Neglect was more common in male patients. Out of the 31 patients suffering from visuospatial neglect, only 16% actually received rotigotine and 80% of them were noted to have an objective improvement in their neglect tests and 20% revealed subjective improvement. After thoroughly going through neglect-associated documentation, the following recommendations/plans were put in place for the future. We plan to liaise with the occupational therapy team at our rehab unit to set a battery of tests that would be done on all patients presenting with neglect and recommend clear documentation of outcomes of each neglect screen under it. Also to create two proformas; one for the therapy team to aid in systematic documentation of neglect screens done prior to and after rotigotine administration and a second proforma for the medical team with clear documentation of rotigotine use, its benefits and any contraindications if not administered.Keywords: hemispatial Neglect, right hemispheric stroke, rotigotine, neglect, dopamine agonist
Procedia PDF Downloads 73435 Outcome of Naive SGLT2 Inhibitors Among ICU Admitted Acute Stroke with T2DM Patients a Prospective Cohort Study in NCMultispecialty Hospital, Biratnagar, Nepal
Authors: Birendra Kumar Bista, Rhitik Bista, Prafulla Koirala, Lokendra Mandal, Nikrsh Raj Shrestha, Vivek Kattel
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Introduction: Poorly controlled diabetes is associated with cause and poor outcome of stroke. High blood sugar reduces cerebral blood flow, increases intracranial pressure, cerebral edema and neuronal death, especially among patients with poorly controlled diabetes.1 SGLT2 inhibitors are associated with 50% reduction in hemorrhagic stroke compared with placebo. SGLT2 inhibitors decrease cardiovascular events via reducing glucose, blood pressure, weight, arteriosclerosis, albuminuria and reduction of atrial fibrillation.2,3 No study has been documented in low income countries to see the role of post stroke SGLT2 inhibitors on diabetic patients at and after ICU admission. Aims: The aim of the study was to measure the 12 months outcome of diabetic patients with acute stroke admitted in ICU set up with naïve SGLT2 inhibitors add on therapy. Method: It was prospective cohort study carried out in a 250 bedded tertiary neurology care hospital at the province capital Biratnagar Nepal. Diabetic patient with acute stroke admitted in ICU from 1st January 2022 to 31st December 2022 who were not under SGLT2 inhibitors were included in the study. These patients were managed as per hospital protocol. Empagliflozin was added to the alternate enrolled patients. Empagliflozin was continued at the time of discharged and during follow up unless contraindicated. These patients were followed up for 12 months. Outcome measured were mortality, morbidity requiring readmission or hospital visit other than regular follow up, SGLT2 inhibitors related adverse events, neuropsychiatry comorbidity, functional status and biochemical parameters. Ethical permission was taken from hospital administration and ethical board. Results: Among 147 diabetic cases 68 were not treated with empagliflozin whereas 67 cases were started the SGLT2 inhibitors. HbA1c level and one year mortality was significantly low among patients on empaglifozin arm. Over a period of 12 months 427 acute stroke patients were admitted in the ICU. Out of them 44% were female, 61% hypertensive, 34% diabetic, 57% dyslipidemia, 26% smoker and with median age of 45 years. Among 427 cases 4% required neurosurgical interventions and 76% had hemorrhagic CVA. The most common reason for ICU admission was GCS<8 (51%). The median ICU stay was 5 days. ICU mortality was 21% whereas 1 year mortality was 41% with most common reason being pneumonia. Empaglifozin related adverse effect was seen in 11% most commonly lower urinary tract infection in 6%. Conclusion: Empagliflozin can safely be started among acute stroke with better Hba1C control and low mortality outcome compared to treatment without SGLT2 inhibitor.Keywords: diabetes, ICU, mortality, SGLT2 inhibitors, stroke
Procedia PDF Downloads 60434 Study on the Use of Manganese-Containing Materials as a Micro Fertilizer Based on the Local Mineral Resources and Industrial Wastes in Hydroponic Systems
Authors: Marine Shavlakadze
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Hydroponic greenhouses systems (production of the artificial substrate without soil) are becoming popular in the world. Mostly the system is used to grow vegetables and berries. Different countries are taking action to participate in the development of hydroponic technology and solutions such as EU members, Turkey, Australia, New Zealand, Israel, Scandinavian countries, etc. Many vegetables and berries are grown by hydroponics in Europe. As a result of our research, we have obtained material containing manganese and nitrogen. It became possible to produce this fertilizer by means of one-stage thermal processing, using industrial waste containing manganese (ores and sludges) and mineral substance (ammonium nitrate) that exist in Georgia. The received material is usable as a micro-fertilizer with economic efficiency. It became possible to turn practically water-insoluble manganese dioxide substance into the soluble condition from industrial waste in an indirect way. The ability to use the material as a fertilizer is predetermined by its chemical and phase composition, as the amount of the active component of the material in relation to manganese is 30%. At the same time, the active component elements presented non-ballast sustained action compounds. The studies implemented in Poland and in Georgia by us have shown that the manganese-containing micro-fertilizer- Mn(NO3)2 can provide the plant with nitrate nitrogen, which is a form that can be used for plants, providing the economy and simplicity of the application of fertilizers. Given the fact that the application of the manganese-containing micro-fertilizers significantly increases the productivity and improves the quality of the big number of agricultural products, it is necessary to mention that it is recommended to introduce the manganese containing fertilizers into the following cultures: sugar beet, corn, potato, vegetables, vine grape, fruit, berries, and other cultures. Also, as a result of the study, it was established that the material obtained is the predominant fertilizer for vegetable cultures in the soil. Based on the positive results of the research, we consider it expedient to conduct research in hydroponic systems, which will enable us to provide plants the required amount of manganese; we also introduce nitrogen in solution and regulate the solution of pH, which is one of the main problems in hydroponic production. The findings of our research will be used in hydroponic greenhouse farms to increase the fertility of vegetable crops and, consequently, to get bountiful and high-quality harvests, which will promote the development of hydroponic greenhouses in Georgia as well as abroad.Keywords: hydroponics, micro-fertilizers, manganese-containing materials, industrial wastes
Procedia PDF Downloads 129433 Synergistic Effect of Chondroinductive Growth Factors and Synovium-Derived Mesenchymal Stem Cells on Regeneration of Cartilage Defects in Rabbits
Authors: M. Karzhauov, А. Mukhambetova, M. Sarsenova, E. Raimagambetov, V. Ogay
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Regeneration of injured articular cartilage remains one of the most difficult and unsolved problems in traumatology and orthopedics. Currently, for the treatment of cartilage defects surgical techniques for stimulation of the regeneration of cartilage in damaged joints such as multiple microperforation, mosaic chondroplasty, abrasion and microfractures is used. However, as shown by clinical practice, they can not provide a full and sustainable recovery of articular hyaline cartilage. In this regard, the current high hopes in the regeneration of cartilage defects reasonably are associated with the use of tissue engineering approaches to restore the structural and functional characteristics of damaged joints using stem cells, growth factors and biopolymers or scaffolds. The purpose of the present study was to investigate the effects of chondroinductive growth factors and synovium-derived mesenchymal stem cells (SD-MSCs) on the regeneration of cartilage defects in rabbits. SD-MSCs were isolated from the synovium membrane of Flemish giant rabbits, and expanded in complete culture medium α-MEM. Rabbit SD-MSCs were characterized by CFU-assay and by their ability to differentiate into osteoblasts, chondrocytes and adipocytes. The effects of growth factors (TGF-β1, BMP-2, BMP-4 and IGF-I) on MSC chondrogenesis were examined in micromass pellet cultures using histological and biochemical analysis. Articular cartilage defect (4mm in diameter) in the intercondylar groove of the patellofemoral joint was performed with a kit for the mosaic chondroplasty. The defect was made until subchondral bone plate. Delivery of SD-MSCs and growth factors was conducted in combination with hyaloronic acid (HA). SD-MSCs, growth factors and control groups were compared macroscopically and histologically at 10, 30, 60 and 90 days aftrer intra-articular injection. Our in vitro comparative study revealed that TGF-β1 and BMP-4 are key chondroinductive factors for both the growth and chondrogenesis of SD-MSCs. The highest effect on MSC chondrogenesis was observed with the synergistic interaction of TGF-β1 and BMP-4. In addition, biochemical analysis of the chondrogenic micromass pellets also revealed that the levels of glycosaminoglycans and DNA after combined treatment with TGF-β1 and BMP-4 was significantly higher in comparison to individual application of these factors. In vivo study showed that for complete regeneration of cartilage defects with intra-articular injection of SD-MSCs with HA takes time 90 days. However, single injection of SD-MSCs in combiantion with TGF-β1, BMP-4 and HA significantly promoted regeneration rate of the cartilage defects in rabbits. In this case, complete regeneration of cartilage defects was observed in 30 days after intra-articular injection. Thus, our in vitro and in vivo study demonstrated that combined application of rabbit SD-MSC with chondroinductive growth factors and HA results in strong synergistic effect on the chondrogenesis significantly enhancing regeneration of the damaged cartilage.Keywords: Mesenchymal stem cells, synovium, chondroinductive factors, TGF-β1, BMP-2, BMP-4, IGF-I
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