Search results for: Jingjing Zhang
Commenced in January 2007
Frequency: Monthly
Edition: International
Paper Count: 1015

Search results for: Jingjing Zhang

55 Novel EGFR Ectodomain Mutations and Resistance to Anti-EGFR and Radiation Therapy in H&N Cancer

Authors: Markus Bredel, Sindhu Nair, Hoa Q. Trummell, Rajani Rajbhandari, Christopher D. Willey, Lewis Z. Shi, Zhuo Zhang, William J. Placzek, James A. Bonner

Abstract:

Purpose: EGFR-targeted monoclonal antibodies (mAbs) provide clinical benefit in some patients with H&N squamous cell carcinoma (HNSCC), but others progress with minimal response. Missense mutations in the EGFR ectodomain (ECD) can be acquired under mAb therapy by mimicking the effect of large deletions on receptor untethering and activation. Little is known about the contribution of EGFR ECD mutations to EGFR activation and anti-EGFR response in HNSCC. Methods: We selected patient-derived HNSCC cells (UM-SCC-1) for resistance to mAb Cetuximab (CTX) by repeated, stepwise exposure to mimic what may occur clinically and identified two concurrent EGFR ECD mutations (UM-SCC-1R). We examined the competence of the mutants to bind EGF ligand or CTX. We assessed the potential impact of the mutations through visual analysis of space-filling models of the native sidechains in the original structures vs. their respective side-chain mutations. We performed CRISPR in combination with site-directed mutagenesis to test for the effect of the mutants on ligand-independent EGFR activation and sorting. We determined the effects on receptor internalization, endocytosis, downstream signaling, and radiation sensitivity. Results: UM-SCC-1R cells carried two non-synonymous missense mutations (G33S and N56K) mapping to domain I in or near the EGF binding pocket of the EGFR ECD. Structural modeling predicted that these mutants restrict the adoption of a tethered, inactive EGFR conformation while not permitting association of EGFR with the EGF ligand or CTX. Binding studies confirmed that the mutant, untethered receptor displayed a reduced affinity for both EGF and CTX but demonstrated sustained activation and presence at the cell surface with diminished internalization and sorting for endosomal degradation. Single and double-mutant models demonstrated that the G33S mutant is dominant over the N56K mutant in its effect on EGFR activation and EGF binding. CTX-resistant UM-SCC-1R cells demonstrated cross-resistance to mAb Panitumuab but, paradoxically, remained sensitive to the reversible receptor tyrosine kinase inhibitor Erlotinib. Conclusions: HNSCC cells can select for EGFR ECD mutations under EGFR mAb exposure that converge to trap the receptor in an open, constitutively activated state. These mutants impede the receptor’s competence to bind mAbs and EGF ligand and alter its endosomal trafficking, possibly explaining certain cases of clinical mAb and radiation resistance.

Keywords: head and neck cancer, EGFR mutation, resistance, cetuximab

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54 Fabrication of High-Aspect Ratio Vertical Silicon Nanowire Electrode Arrays for Brain-Machine Interfaces

Authors: Su Yin Chiam, Zhipeng Ding, Guang Yang, Danny Jian Hang Tng, Peiyi Song, Geok Ing Ng, Ken-Tye Yong, Qing Xin Zhang

Abstract:

Brain-machine interfaces (BMI) is a ground rich of exploration opportunities where manipulation of neural activity are used for interconnect with myriad form of external devices. These research and intensive development were evolved into various areas from medical field, gaming and entertainment industry till safety and security field. The technology were extended for neurological disorders therapy such as obsessive compulsive disorder and Parkinson’s disease by introducing current pulses to specific region of the brain. Nonetheless, the work to develop a real-time observing, recording and altering of neural signal brain-machine interfaces system will require a significant amount of effort to overcome the obstacles in improving this system without delay in response. To date, feature size of interface devices and the density of the electrode population remain as a limitation in achieving seamless performance on BMI. Currently, the size of the BMI devices is ranging from 10 to 100 microns in terms of electrodes’ diameters. Henceforth, to accommodate the single cell level precise monitoring, smaller and denser Nano-scaled nanowire electrode arrays are vital in fabrication. In this paper, we would like to showcase the fabrication of high aspect ratio of vertical silicon nanowire electrodes arrays using microelectromechanical system (MEMS) method. Nanofabrication of the nanowire electrodes involves in deep reactive ion etching, thermal oxide thinning, electron-beam lithography patterning, sputtering of metal targets and bottom anti-reflection coating (BARC) etch. Metallization on the nanowire electrode tip is a prominent process to optimize the nanowire electrical conductivity and this step remains a challenge during fabrication. Metal electrodes were lithographically defined and yet these metal contacts outline a size scale that is larger than nanometer-scale building blocks hence further limiting potential advantages. Therefore, we present an integrated contact solution that overcomes this size constraint through self-aligned Nickel silicidation process on the tip of vertical silicon nanowire electrodes. A 4 x 4 array of vertical silicon nanowires electrodes with the diameter of 290nm and height of 3µm has been successfully fabricated.

Keywords: brain-machine interfaces, microelectromechanical systems (MEMS), nanowire, nickel silicide

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53 A Standard-Based Competency Evaluation Scale for Preparing Qualified Adapted Physical Education Teachers

Authors: Jiabei Zhang

Abstract:

Although adapted physical education (APE) teacher preparation programs are available in the nation, a consistent standards-based competency evaluation scale for preparing of qualified personnel for teaching children with disabilities in APE cannot be identified in the literature. The purpose of this study was to develop a standard-based competency evaluation scale for assessing qualifications for teaching children with disabilities in APE. Standard-based competencies were reviewed and identified based on research evidence documented as effective in teaching children with disabilities in APE. A standard-based competency scale was developed for assessing qualifications for teaching children with disabilities in APE. This scale included 20 standard-based competencies and a 4-point Likert-type scale for each standard-based competency. The first standard-based competency is knowledgeable of the causes of disabilities and their effects. The second competency is the ability to assess physical education skills of children with disabilities. The third competency is able to collaborate with other personnel. The fourth competency is knowledgeable of the measurement and evaluation. The fifth competency is to understand federal and state laws. The sixth competency is knowledgeable of the unique characteristics of all learners. The seventh competency is the ability to write in behavioral terms for objectives. The eighth competency is knowledgeable of developmental characteristics. The ninth competency is knowledgeable of normal and abnormal motor behaviors. The tenth competency is the ability to analyze and adapt the physical education curriculums. The eleventh competency is to understand the history and the philosophy of physical education. The twelfth competency is to understand curriculum theory and development. The thirteenth competency is the ability to utilize instructional designs and plans. The fourteenth competency is the ability to create and implement physical activities. The fifteenth competency is the ability to utilize technology applications. The sixteenth competency is to understand the value of program evaluation. The seventeenth competency is to understand professional standards. The eighteenth competency is knowledgeable of the focused instruction and individualized interventions. The nineteenth competency is able to complete a research project independently. The twentieth competency is to teach children with disabilities in APE independently. The 4-point Likert-type scale ranges from 1 for incompetent to 4 for highly competent. This scale is used for assessing if one completing all course works is eligible for receiving an endorsement for teaching children with disabilities in APE, which is completed based on the grades earned on three courses targeted for each standard-based competency. A mean grade received in three courses primarily addressing a standard-based competency will be marked on a competency level in the above scale. The level 4 is marked for a mean grade of A one receives over three courses, the level 3 for a mean grade of B over three courses, and so on. One should receive a mean score of 3 (competent level) or higher (highly competent) across 19 standard-based competencies after completing all courses specified for receiving an endorsement for teaching children with disabilities in APE. The validity, reliability, and objectivity of this standard-based competency evaluation scale are to be documented.

Keywords: evaluation scale, teacher preparation, adapted physical education teachers, and children with disabilities

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52 A Laser Instrument Rapid-E+ for Real-Time Measurements of Airborne Bioaerosols Such as Bacteria, Fungi, and Pollen

Authors: Minghui Zhang, Sirine Fkaier, Sabri Fernana, Svetlana Kiseleva, Denis Kiselev

Abstract:

The real-time identification of bacteria and fungi is difficult because they emit much weaker signals than pollen. In 2020, Plair developed Rapid-E+, which extends abilities of Rapid-E to detect smaller bioaerosols such as bacteria and fungal spores with diameters down to 0.3 µm, while keeping the similar or even better capability for measurements of large bioaerosols like pollen. Rapid-E+ enables simultaneous measurements of (1) time-resolved, polarization and angle dependent Mie scattering patterns, (2) fluorescence spectra resolved in 16 channels, and (3) fluorescence lifetime of individual particles. Moreover, (4) it provides 2D Mie scattering images which give the full information on particle morphology. The parameters of every single bioaerosol aspired into the instrument are subsequently analysed by machine learning. Firstly, pure species of microbes, e.g., Bacillus subtilis (a species of bacteria), and Penicillium chrysogenum (a species of fungal spores), were aerosolized in a bioaerosol chamber for Rapid-E+ training. Afterwards, we tested microbes under different concentrations. We used several steps of data analysis to classify and identify microbes. All single particles were analysed by the parameters of light scattering and fluorescence in the following steps. (1) They were treated with a smart filter block to get rid of non-microbes. (2) By classification algorithm, we verified the filtered particles were microbes based on the calibration data. (3) The probability threshold (defined by the user) step provides the probability of being microbes ranging from 0 to 100%. We demonstrate how Rapid-E+ identified simultaneously microbes based on the results of Bacillus subtilis (bacteria) and Penicillium chrysogenum (fungal spores). By using machine learning, Rapid-E+ achieved identification precision of 99% against the background. The further classification suggests the precision of 87% and 89% for Bacillus subtilis and Penicillium chrysogenum, respectively. The developed algorithm was subsequently used to evaluate the performance of microbe classification and quantification in real-time. The bacteria and fungi were aerosolized again in the chamber with different concentrations. Rapid-E+ can classify different types of microbes and then quantify them in real-time. Rapid-E+ enables classifying different types of microbes and quantifying them in real-time. Rapid-E+ can identify pollen down to species with similar or even better performance than the previous version (Rapid-E). Therefore, Rapid-E+ is an all-in-one instrument which classifies and quantifies not only pollen, but also bacteria and fungi. Based on the machine learning platform, the user can further develop proprietary algorithms for specific microbes (e.g., virus aerosols) and other aerosols (e.g., combustion-related particles that contain polycyclic aromatic hydrocarbons).

Keywords: bioaerosols, laser-induced fluorescence, Mie-scattering, microorganisms

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51 Product Life Cycle Assessment of Generatively Designed Furniture for Interiors Using Robot Based Additive Manufacturing

Authors: Andrew Fox, Qingping Yang, Yuanhong Zhao, Tao Zhang

Abstract:

Furniture is a very significant subdivision of architecture and its inherent interior design activities. The furniture industry has developed from an artisan-driven craft industry, whose forerunners saw themselves manifested in their crafts and treasured a sense of pride in the creativity of their designs, these days largely reduced to an anonymous collective mass-produced output. Although a very conservative industry, there is great potential for the implementation of collaborative digital technologies allowing a reconfigured artisan experience to be reawakened in a new and exciting form. The furniture manufacturing industry, in general, has been slow to adopt new methodologies for a design using artificial and rule-based generative design. This tardiness has meant the loss of potential to enhance its capabilities in producing sustainable, flexible, and mass customizable ‘right first-time’ designs. This paper aims to demonstrate the concept methodology for the creation of alternative and inspiring aesthetic structures for robot-based additive manufacturing (RBAM). These technologies can enable the economic creation of previously unachievable structures, which traditionally would not have been commercially economic to manufacture. The integration of these technologies with the computing power of generative design provides the tools for practitioners to create concepts which are well beyond the insight of even the most accomplished traditional design teams. This paper aims to address the problem by introducing generative design methodologies employing the Autodesk Fusion 360 platform. Examination of the alternative methods for its use has the potential to significantly reduce the estimated 80% contribution to environmental impact at the initial design phase. Though predominantly a design methodology, generative design combined with RBAM has the potential to leverage many lean manufacturing and quality assurance benefits, enhancing the efficiency and agility of modern furniture manufacturing. Through a case study examination of a furniture artifact, the results will be compared to a traditionally designed and manufactured product employing the Ecochain Mobius product life cycle analysis (LCA) platform. This will highlight the benefits of both generative design and robot-based additive manufacturing from an environmental impact and manufacturing efficiency standpoint. These step changes in design methodology and environmental assessment have the potential to revolutionise the design to manufacturing workflow, giving momentum to the concept of conceiving a pre-industrial model of manufacturing, with the global demand for a circular economy and bespoke sustainable design at its heart.

Keywords: robot, manufacturing, generative design, sustainability, circular econonmy, product life cycle assessment, furniture

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50 Rational Approach to Analysis and Construction of Curved Composite Box Girders in Bridges

Authors: Dongming Feng, Fangyin Zhang, Liling Cao

Abstract:

Horizontally curved steel-concrete composite box girders are extensively used in highway bridges. They consist of reinforced concrete deck on top of prefabricated steel box section beam which exhibits a high torsional rigidity to resist torsional effects induced by the curved structural geometry. This type of structural system is often constructed in two stages. The composite section will take the tension mainly by the steel box and, the compression by the concrete deck. The steel girders are delivered in large pre-fabricated U-shaped sections that are designed for ease of construction. They are then erected on site and overlaid by cast-in-place reinforced concrete deck. The functionality of the composite section is not achieved until the closed section is formed by fully cured concrete. Since this kind of composite section is built in two stages, the erection of the open steel box presents some challenges to contractors. When the reinforced concrete slab is cast-in-place, special care should be taken on bracings that can prevent the open U-shaped steel box from global and local buckling. In the case of multiple steel boxes, the design detailing should pay enough attention to the installation requirement of the bracings connecting adjacent steel boxes to prevent the global buckling. The slope in transverse direction and grade in longitudinal direction will result in some local deformation of the steel boxes that affect the connection of the bracings. During the design phase, it is common for engineers to model the curved composite box girder using one-dimensional beam elements. This is adequate to analyze the global behavior, however, it is unable to capture the local deformation which affects the installation of the field bracing connection. The presence of the local deformation may become a critical component to control the construction tolerance, and overlooking this deformation will produce inadequate structural details that eventually cause misalignment in field and erection failure. This paper will briefly describe the construction issues we encountered in real structures, investigate the difference between beam element modeling and shell/solid element modeling, and their impact on the different construction stages. P-delta effect due to the slope and curvature of the composite box girder is analyzed, and the secondary deformation is compared to the first-order response and evaluated for its impact on installation of lateral bracings. The paper will discuss the rational approach to prepare construction documents and recommendations are made on the communications between engineers, erectors, and fabricators to smooth out construction process.

Keywords: buckling, curved composite box girder, stage construction, structural detailing

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49 Superlyophobic Surfaces for Increased Heat Transfer during Condensation of CO₂

Authors: Ingrid Snustad, Asmund Ervik, Anders Austegard, Amy Brunsvold, Jianying He, Zhiliang Zhang

Abstract:

CO₂ capture, transport and storage (CCS) is essential to mitigate global anthropogenic CO₂ emissions. To make CCS a widely implemented technology in, e.g. the power sector, the reduction of costs is crucial. For a large cost reduction, every part of the CCS chain must contribute. By increasing the heat transfer efficiency during liquefaction of CO₂, which is a necessary step, e.g. ship transportation, the costs associated with the process are reduced. Heat transfer rates during dropwise condensation are up to one order of magnitude higher than during filmwise condensation. Dropwise condensation usually occurs on a non-wetting surface (Superlyophobic surface). The vapour condenses in discrete droplets, and the non-wetting nature of the surface reduces the adhesion forces and results in shedding of condensed droplets. This, again, results in fresh nucleation sites for further droplet condensation, effectively increasing the liquefaction efficiency. In addition, the droplets in themselves have a smaller heat transfer resistance than a liquid film, resulting in increased heat transfer rates from vapour to solid. Surface tension is a crucial parameter for dropwise condensation, due to its impact on the solid-liquid contact angle. A low surface tension usually results in a low contact angle, and again to spreading of the condensed liquid on the surface. CO₂ has very low surface tension compared to water. However, at relevant temperatures and pressures for CO₂ condensation, the surface tension is comparable to organic compounds such as pentane, a dropwise condensation of CO₂ is a completely new field of research. Therefore, knowledge of several important parameters such as contact angle and drop size distribution must be gained in order to understand the nature of the condensation. A new setup has been built to measure these relevant parameters. The main parts of the experimental setup is a pressure chamber in which the condensation occurs, and a high- speed camera. The process of CO₂ condensation is visually monitored, and one can determine the contact angle, contact angle hysteresis and hence, the surface adhesion of the liquid. CO₂ condensation on different surfaces can be analysed, e.g. copper, aluminium and stainless steel. The experimental setup is built for accurate measurements of the temperature difference between the surface and the condensing vapour and accurate pressure measurements in the vapour. The temperature will be measured directly underneath the condensing surface. The next step of the project will be to fabricate nanostructured surfaces for inducing superlyophobicity. Roughness is a key feature to achieve contact angles above 150° (limit for superlyophobicity) and controlled, and periodical roughness on the nanoscale is beneficial. Surfaces that are non- wetting towards organic non-polar liquids are candidates surface structures for dropwise condensation of CO₂.

Keywords: CCS, dropwise condensation, low surface tension liquid, superlyophobic surfaces

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48 Accounting for Downtime Effects in Resilience-Based Highway Network Restoration Scheduling

Authors: Zhenyu Zhang, Hsi-Hsien Wei

Abstract:

Highway networks play a vital role in post-disaster recovery for disaster-damaged areas. Damaged bridges in such networks can disrupt the recovery activities by impeding the transportation of people, cargo, and reconstruction resources. Therefore, rapid restoration of damaged bridges is of paramount importance to long-term disaster recovery. In the post-disaster recovery phase, the key to restoration scheduling for a highway network is prioritization of bridge-repair tasks. Resilience is widely used as a measure of the ability to recover with which a network can return to its pre-disaster level of functionality. In practice, highways will be temporarily blocked during the downtime of bridge restoration, leading to the decrease of highway-network functionality. The failure to take downtime effects into account can lead to overestimation of network resilience. Additionally, post-disaster recovery of highway networks is generally divided into emergency bridge repair (EBR) in the response phase and long-term bridge repair (LBR) in the recovery phase, and both of EBR and LBR are different in terms of restoration objectives, restoration duration, budget, etc. Distinguish these two phases are important to precisely quantify highway network resilience and generate suitable restoration schedules for highway networks in the recovery phase. To address the above issues, this study proposes a novel resilience quantification method for the optimization of long-term bridge repair schedules (LBRS) taking into account the impact of EBR activities and restoration downtime on a highway network’s functionality. A time-dependent integer program with recursive functions is formulated for optimally scheduling LBR activities. Moreover, since uncertainty always exists in the LBRS problem, this paper extends the optimization model from the deterministic case to the stochastic case. A hybrid genetic algorithm that integrates a heuristic approach into a traditional genetic algorithm to accelerate the evolution process is developed. The proposed methods are tested using data from the 2008 Wenchuan earthquake, based on a regional highway network in Sichuan, China, consisting of 168 highway bridges on 36 highways connecting 25 cities/towns. The results show that, in this case, neglecting the bridge restoration downtime can lead to approximately 15% overestimation of highway network resilience. Moreover, accounting for the impact of EBR on network functionality can help to generate a more specific and reasonable LBRS. The theoretical and practical values are as follows. First, the proposed network recovery curve contributes to comprehensive quantification of highway network resilience by accounting for the impact of both restoration downtime and EBR activities on the recovery curves. Moreover, this study can improve the highway network resilience from the organizational dimension by providing bridge managers with optimal LBR strategies.

Keywords: disaster management, highway network, long-term bridge repair schedule, resilience, restoration downtime

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47 Influence of Synergistic Modification with Tung Oil and Heat Treatment on Physicochemical Properties of Wood

Authors: Luxi He, Tianfang Zhang, Zhengbin He, Songlin Yi

Abstract:

Heat treatment has been widely recognized for its effectiveness in enhancing the physicochemical properties of wood, including hygroscopicity and dimensional stability. Nonetheless, the non-negligible volumetric shrinkage and loss of mechanical strength resulting from heat treatment may diminish the wood recovery and its product value. In this study, tung oil was used to alleviate heat-induced shrinkage and reduction in mechanical properties of wood during heat treatment. Tung oil was chosen as a modifier because it is a traditional Chinese plant oil that has been widely used for over a thousand years to protect wooden furniture and buildings due to its biodegradable and non-toxic properties. The effects of different heating media (air, tung oil) and their effective treatment parameters (temperature, duration) on the changes in the physical properties (morphological characteristics, pore structures, micromechanical properties), and chemical properties (chemical structures, chemical composition) of wood were investigated by using scanning electron microscopy, confocal laser scanning microscopy, atomic force microscopy, X-ray photoelectron spectroscopy, and dynamic vapor sorption. Meanwhile, the correlation between the mass changes and the color change, volumetric shrinkage, and hygroscopicity was also investigated. The results showed that the thermal degradation of wood cell wall components was the most important factor contributing to the changes in heat-induced shrinkage, color, and moisture adsorption of wood. In air-heat-treated wood samples, there was a significant correlation between mass change and heat-induced shrinkage, brightness, and moisture adsorption. However, the presence of impregnated tung oil in oil-heat-treated wood appears to disrupt these correlations among physical properties. The results of micromechanical properties demonstrated a significant decrease in elastic modulus following high-temperature heat treatment, which was mitigated by tung oil treatment. Chemical structure and compositional analyses indicated that the changes in chemical structure primarily stem from the degradation of hemicellulose and cellulose, and the presence of tung oil created an oxygen-insulating environment that slowed down this degradation process. Morphological observation results showed that tung oil permeated the wood structure and penetrated the cell walls through transportation channels, altering the micro-morphology of the cell wall surface, obstructing primary water passages (e.g., vessels and pits), and impeding the release of volatile degradation products as well as the infiltration and diffusion of water. In summary, tung oil treatment represents an environmentally friendly and efficient method for maximizing wood recovery and increasing product value. This approach holds significant potential for industrial applications in wood heat treatment.

Keywords: tung oil, heat treatment, physicochemical properties, wood cell walls

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46 Shale Gas Accumulation of Over-Mature Cambrian Niutitang Formation Shale in Structure-Complicated Area, Southeastern Margin of Upper Yangtze, China

Authors: Chao Yang, Jinchuan Zhang, Yongqiang Xiong

Abstract:

The Lower Cambrian Niutitang Formation shale (NFS) deposited in the marine deep-shelf environment in Southeast Upper Yangtze (SUY), possess excellent source rock basis for shale gas generation, however, it is currently challenged by being over-mature with strong tectonic deformations, leading to much uncertainty of gas-bearing potential. With emphasis on the shale gas enrichment of the NFS, analyses were made based on the regional gas-bearing differences obtained from field gas-desorption testing of 18 geological survey wells across the study area. Results show that the NFS bears low gas content of 0.2-2.5 m³/t, and the eastern region of SUY is higher than the western region in gas content. Moreover, the methane fraction also presents the similar regional differentiation with the western region less than 10 vol.% while the eastern region generally more than 70 vol.%. Through the analysis of geological theory, the following conclusions are drawn: Depositional environment determines the gas-enriching zones. In the western region, the Dengying Formation underlying the NFS in unconformity contact was mainly plateau facies dolomite with caves and thereby bears poor gas-sealing ability. Whereas the Laobao Formation underling the NFS in eastern region was a set of siliceous rocks of shelf-slope facies, which can effectively prevent the shale gas from escaping away from the NFS. The tectonic conditions control the gas-enriching bands in the SUY, which is located in the fold zones formed by the thrust of the Southern China plate towards to the Sichuan Basin. Compared with the western region located in the trough-like folds, the eastern region at the fold-thrust belts was uplifted early and deformed weakly, resulting in the relatively less mature level and relatively slight tectonic deformation of the NFS. Faults determine whether shale gas can be accumulated in large scale. Four deep and large normal faults in the study area cut through the Niutitang Formation to the Sinian strata, directly causing a large spillover of natural gas in the adjacent areas. For the secondary faults developed within the shale formation, the reverse faults generally have a positive influence on the shale accumulation while the normal faults perform the opposite influence. Overall, shale gas enrichment targets of the NFS, are the areas with certain thickness of siliceous rocks at the basement of the Niutitang Formation, and near the margin of the paleouplift with less developed faults. These findings provide direction for shale gas exploration in South China, and also provide references for the areas with similar geological conditions all over the world.

Keywords: over-mature marine shale, shale gas accumulation, structure-complicated area, Southeast Upper Yangtze

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45 A Holistic View of Microbial Community Dynamics during a Toxic Harmful Algal Bloom

Authors: Shi-Bo Feng, Sheng-Jie Zhang, Jin Zhou

Abstract:

The relationship between microbial diversity and algal bloom has received considerable attention for decades. Microbes undoubtedly affect annual bloom events and impact the physiology of both partners, as well as shape ecosystem diversity. However, knowledge about interactions and network correlations among broader-spectrum microbes that lead to the dynamics in a complete bloom cycle are limited. In this study, pyrosequencing and network approaches simultaneously assessed the associate patterns among bacteria, archaea, and microeukaryotes in surface water and sediments in response to a natural dinoflagellate (Alexandrium sp.) bloom. In surface water, among the bacterial community, Gamma-Proteobacteria and Bacteroidetes dominated in the initial bloom stage, while Alpha-Proteobacteria, Cyanobacteria, and Actinobacteria become the most abundant taxa during the post-stage. In the archaea biosphere, it clustered predominantly with Methanogenic members in the early pre-bloom period while the majority of species identified in the later-bloom stage were ammonia-oxidizing archaea and Halobacteriales. In eukaryotes, dinoflagellate (Alexandrium sp.) was dominated in the onset stage, whereas multiply species (such as microzooplankton, diatom, green algae, and rotifera) coexistence in bloom collapse stag. In sediments, the microbial species biomass and richness are much higher than the water body. Only Flavobacteriales and Rhodobacterales showed a slight response to bloom stages. Unlike the bacteria, there are small fluctuations of archaeal and eukaryotic structure in the sediment. The network analyses among the inter-specific associations show that bacteria (Alteromonadaceae, Oceanospirillaceae, Cryomorphaceae, and Piscirickettsiaceae) and some zooplankton (Mediophyceae, Mamiellophyceae, Dictyochophyceae and Trebouxiophyceae) have a stronger impact on the structuring of phytoplankton communities than archaeal effects. The changes in population were also significantly shaped by water temperature and substrate availability (N & P resources). The results suggest that clades are specialized at different time-periods and that the pre-bloom succession was mainly a bottom-up controlled, and late-bloom period was controlled by top-down patterns. Additionally, phytoplankton and prokaryotic communities correlated better with each other, which indicate interactions among microorganisms are critical in controlling plankton dynamics and fates. Our results supplied a wider view (temporal and spatial scales) to understand the microbial ecological responses and their network association during algal blooming. It gives us a potential multidisciplinary explanation for algal-microbe interaction and helps us beyond the traditional view linked to patterns of algal bloom initiation, development, decline, and biogeochemistry.

Keywords: microbial community, harmful algal bloom, ecological process, network

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44 Physical Contact Modulation of Macrophage-Mediated Anti-Inflammatory Response in Osteoimmune Microenvironment by Pollen-Like Nanoparticles

Authors: Qing Zhang, Janak L. Pathak, Macro N. Helder, Richard T. Jaspers, Yin Xiao

Abstract:

Introduction: Nanomaterial-based bone regeneration is greatly influenced by the immune microenvironment. Tissue-engineered nanomaterials mediate the inflammatory response of macrophages to regulate bone regeneration. Silica nanoparticles have been widely used in tissue engineering-related preclinical studies. However, the effect of topological features on the surface of silica nanoparticles on the immune response of macrophages remains unknown. Purposes: The aims of this research are to compare the influences of normal and pollen-like silica nano-surface topography on macrophage immune responses and to obtain insight into their potential regulatory mechanisms. Method: Macrophages (RAW 264.7 cells) were exposed to mesoporous silica nanoparticles with normal morphology (MSNs) and pollen-like morphology (PMSNs). RNA-seq, RT-qPCR, and LSCM were used to assess the changes in expression levels of immune response-related genes and proteins. SEM and TEM were executed to evaluate the contact and adherence of silica nanoparticles by macrophages. For the assessment of the immunomodulation-mediated osteogenic potential, BMSCs were cultured with conditioned medium (CM) from LPS pre-stimulated macrophage cultures treated with MSNs or PMSNs. Osteoimmunomodulatory potential of MSNs and PMSNs in vivo was tested in a mouse cranial bone osteolysis model. Results: The results of the RNA-seq, RT-qPCR, and LSCM assays showed that PMSNs inhibited the expression of pro-inflammatory genes and proteins in macrophages. SEM images showed distinct macrophage membrane surface binding patterns of MSNs and PMSNs. MSNs were more evenly dispersed across the macrophage cell membrane, while PMSNs were aggregated. PMSNs-induced macrophage anti-inflammatory response was associated with upregulation of the cell surface receptor CD28 and inhibition of ERK phosphorylation. TEM images showed that both MSNs and PMSNs could be phagocytosed by macrophages, and inhibiting nanoparticle phagocytosis did not affect the expression of anti-inflammatory genes and proteins. Moreover, PMSNs-induced conditioned medium from macrophages enhanced BMP-2 expression and osteogenic differentiation mBMSCs. Similarly, PMSNs prevented LPS-induced bone resorption via downregulation of inflammatory reaction. Conclusions: PMSNs can promote bone regeneration by modulating osteoimmunological processes through surface topography. The study offers insights into how surface physical contact cues can modulate the regulation of osteoimmunology and provides a basis for the application of nanoparticles with pollen-like morphology to affect immunomodulation in bone tissue engineering and regeneration.

Keywords: physical contact, osteoimmunology, macrophages, silica nanoparticles, surface morphology, membrane receptor, osteogenesis, inflammation

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43 Expecting and Experiencing Negotiated Internationalisation: Lived Engagement of Chinese Students in an International Joint University

Authors: Bowen Zhang

Abstract:

Transnational higher education (TNHE) is one of the most prominent symbols of higher education’s internationalisation. The case university, Xi'an Jiaotong Liverpool University (XJTLU), represents an equal collaboration between its parent institutions as they are tied in academic strength. Therefore, compared to the more prescribed route of UNNC, which is working towards creating another UK university in China, XJTLU’s future is fraught with uncertainty. Such kind of uncertainty underpins the rationale of selecting XJTLU as a case university in researching internationalisation -it does not aim to build an international university based on a template; instead, internationalisation in XJTLU is established in a more participatory manner that also reflects an understanding of its staff and students. Therefore, this article focuses on Chinese students' expectations and experiences in XJTLU. While there are research discussing international students' experiences in TNHE institutions, the experiences of Chinese students who attend their domestic TNHE have been less explored. This might be due to the potential issues they confront are not as intuitive as those faced by international students, whose experiences are largely shaped by mobility and cross-cultural transition, a well-documented and conceptualised phenomenon. Research regarding Chinese students mainly focuses on their motivations, for example, enhancing English proficiency, improving competitive advantage in labour market, and gaining an international perspective. However, it should be noted that these motivations are based on the internationalised features of TNHE institutions. Internationalisation in XJTLU is symbolised through 100% English-medium instruction, internationalised curriculum, and the national diversity of its students and staff. However, in practice, these promises for internationalisation are hardly met; for example, in terms of EMI, lecturers may engage in their native language, either out of their hope to enhance students’ understanding or forcibly switch back to Chinese due to limited language capacity. Therefore, it could be seen that the non-application of internationalised policy may result in a negotiated internationalising experience for students. It is important to point out that, in this study, both the expected capital that students hope to access prior to their enrollment to XJTLU and the actual capital that students are accumulating during their attendance, are examined, as the difference between the actual and potential could be an important indicator of the discrepancy between how internationalisation is perceived and how it is enacted in practice. The potential resources implicate perceived compatibility between habitus and field, which is highly relevant to the way that a field makes itself known, whereas the actual resources represent the lived experience and the actual compatibility between habitus and field. This study explores the similarities and differences between the expected and lived capital from XJTLU, and the way that students form and navigate their expectations, in turn providing insights on how XJTLU, or HE internationalisation as a whole, is depicted, imagined, and enacted among Chinese students.

Keywords: transnational higher education, English-medium instruction, students' experience, Chinese higher education

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42 Synergy Surface Modification for High Performance Li-Rich Cathode

Authors: Aipeng Zhu, Yun Zhang

Abstract:

The growing grievous environment problems together with the exhaustion of energy resources put urgent demands for developing high energy density. Considering the factors including capacity, resource and environment, Manganese-based lithium-rich layer-structured cathode materials xLi₂MnO₃⋅(1-x)LiMO₂ (M = Ni, Co, Mn, and other metals) are drawing increasing attention due to their high reversible capacities, high discharge potentials, and low cost. They are expected to be one type of the most promising cathode materials for the next-generation Li-ion batteries (LIBs) with higher energy densities. Unfortunately, their commercial applications are hindered with crucial drawbacks such as poor rate performance, limited cycle life and continuous falling of the discharge potential. With decades of extensive studies, significant achievements have been obtained in improving their cyclability and rate performances, but they cannot meet the requirement of commercial utilization till now. One major problem for lithium-rich layer-structured cathode materials (LLOs) is the side reaction during cycling, which leads to severe surface degradation. In this process, the metal ions can dissolve in the electrolyte, and the surface phase change can hinder the intercalation/deintercalation of Li ions and resulting in low capacity retention and low working voltage. To optimize the LLOs cathode material, the surface coating is an efficient method. Considering the price and stability, Al₂O₃ was used as a coating material in the research. Meanwhile, due to the low initial Coulombic efficiency (ICE), the pristine LLOs was pretreated by KMnO₄ to increase the ICE. The precursor was prepared by a facile coprecipitation method. The as-prepared precursor was then thoroughly mixed with Li₂CO₃ and calcined in air at 500℃ for 5h and 900℃ for 12h to produce Li₁.₂[Ni₀.₂Mn₀.₆]O₂ (LNMO). The LNMO was then put into 0.1ml/g KMnO₄ solution stirring for 3h. The resultant was filtered and washed with water, and dried in an oven. The LLOs obtained was dispersed in Al(NO₃)₃ solution. The mixture was lyophilized to confer the Al(NO₃)₃ was uniformly coated on LLOs. After lyophilization, the LLOs was calcined at 500℃ for 3h to obtain LNMO@LMO@ALO. The working electrodes were prepared by casting the mixture of active material, acetylene black, and binder (polyvinglidene fluoride) dissolved in N-methyl-2-pyrrolidone with a mass ratio of 80: 15: 5 onto an aluminum foil. The electrochemical performance tests showed that the multiple surface modified materials had a higher initial Coulombic efficiency (84%) and better capacity retention (91% after 100 cycles) compared with that of pristine LNMO (76% and 80%, respectively). The modified material suggests that the KMnO₄ pretreat and Al₂O₃ coating can increase the ICE and cycling stability.

Keywords: Li-rich materials, surface coating, lithium ion batteries, Al₂O₃

Procedia PDF Downloads 133
41 Awareness of 'Psychosocial Restraint': A Proper Caring Attitude and Truly Listening to People with Dementia in the Hong Kong’S Residential Care Homes

Authors: Kenny Chi Man Chui

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Background: In Chinese culture, the traditional equivalent term for English dementia is chi dai zheng, which, whether translated as ‘insanity’ or ‘idiocy’ carries a sharply negative connotation. In fact, even though the traditional name for dementia has evolved, from chi dai zheng to shi zhi zheng, nao tui hua zheng or ren zhi zhang ai zheng, educating the population about more respectful terms for the condition and promoting a positive understanding about people with dementia in society have proven to be time-intensive endeavors. By extension, the use of such terms promotes the perception that people with dementia undergo a ‘total loss of self’ or experience a ‘living death’ or ‘social death’. Both in Asia and elsewhere, the appropriate nomenclature for dementia remains controversial, and different medical and healthcare professionals in Hong Kong have taken various stances on how to refer to the condition there. Indeed, how this negative perception affects the interaction between people with dementia and the surrounding others? Methodology: Qualitative research with the concept of postmodernism, interpretivism, and Foucauldian theory was adopted as frameworks in applying participatory observations, in-depth interviews, and other qualitative methods. First, ten people with dementia—one man and nine women—living in two residential care homes in Hong Kong were interviewed, as were ten members of the care staff, all of whom were women. Next, to coach the staff in understanding the feelings and self-perceptions of people with dementia, two reflective training sessions were provided. Afterward, to assess the impact of the training sessions on the staff, two focus groups were held. Findings: The findings revealed that residents with dementia did not perceive themselves as being ‘demented’ and were confused by not getting responses from the others. From the understanding of care staff, they perceived the residents as being ‘demented’, desolate troublemakers. They described people with dementia as ‘naughty children’ who should be controlled and be punished while treated them as ‘psychiatric patients’ who could be ignored and be mute. “Psychosocial restraint” happened regarding the discrepancy of perception between people with dementia and the care staff. People with dementia did not think that their confusion of memory was related to dementia or, frankly speaking, they did not know what dementia was. When others treated them as ‘demented patients, the residents with mild to moderate dementia fiercely rejected that designation and reported a host of negative feelings, hence the fluctuations of mood and emotion noted by the care staff. Conclusion: As the findings revealed, the people with dementia were also discontent with the care arrangements in the care homes, felt abandoned by others and worried about bothering others. Their shifting emotional states and moods were treated as the Behavioral and Psychological symptoms of Dementia (BPSD), which nothing can do reported by the care staff in the residential care homes. People with dementia become social withdrawal or isolated in daily living, which should be alert and be changed by the social work professionals about the occurrence of “psychosocial restraint” in dementia care.

Keywords: psychosocial restraint, qualitative research, social work with dementitude, voice of people with dementia

Procedia PDF Downloads 180
40 Topology Optimization Design of Transmission Structure in Flapping-Wing Micro Aerial Vehicle via 3D Printing

Authors: Zuyong Chen, Jianghao Wu, Yanlai Zhang

Abstract:

Flapping-wing micro aerial vehicle (FMAV) is a new type of aircraft by mimicking the flying behavior to that of small birds or insects. Comparing to the traditional fixed wing or rotor-type aircraft, FMAV only needs to control the motion of flapping wings, by changing the size and direction of lift to control the flight attitude. Therefore, its transmission system should be designed very compact. Lightweight design can effectively extend its endurance time, while engineering experience alone is difficult to simultaneously meet the requirements of FMAV for structural strength and quality. Current researches still lack the guidance of considering nonlinear factors of 3D printing material when carrying out topology optimization, especially for the tiny FMAV transmission system. The coupling of non-linear material properties and non-linear contact behaviors of FMAV transmission system is a great challenge to the reliability of the topology optimization result. In this paper, topology optimization design based on FEA solver package Altair Optistruct for the transmission system of FMAV manufactured by 3D Printing was carried out. Firstly, the isotropic constitutive behavior of the Ultraviolet (UV) Cureable Resin used to fabricate the structure of FMAV was evaluated and confirmed through tensile test. Secondly, a numerical computation model describing the mechanical behavior of FMAV transmission structure was established and verified by experiments. Then topology optimization modeling method considering non-linear factors were presented, and optimization results were verified by dynamic simulation and experiments. Finally, detail discussions of different load status and constraints were carried out to explore the leading factors affecting the optimization results. The contributions drawn from this article helpful for guiding the lightweight design of FMAV are summarizing as follow; first, a dynamic simulation modeling method used to obtain the load status is presented. Second, verification method of optimized results considering non-linear factors is introduced. Third, based on or can achieve a better weight reduction effect and improve the computational efficiency rather than taking multi-states into account. Fourth, basing on makes for improving the ability to resist bending deformation. Fifth, constraint of displacement helps to improve the structural stiffness of optimized result. Results and engineering guidance in this paper may shed lights on the structural optimization and light-weight design for future advanced FMAV.

Keywords: flapping-wing micro aerial vehicle, 3d printing, topology optimization, finite element analysis, experiment

Procedia PDF Downloads 170
39 Model Tests on Geogrid-Reinforced Sand-Filled Embankments with a Cover Layer under Cyclic Loading

Authors: Ma Yuan, Zhang Mengxi, Akbar Javadi, Chen Longqing

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The structure of sand-filled embankment with cover layer is treated with tipping clay modified with lime on the outside of the packing, and the geotextile is placed between the stuffing and the clay. The packing is usually river sand, and the improved clay protects the sand core against rainwater erosion. The sand-filled embankment with cover layer has practical problems such as high filling embankment, construction restriction, and steep slope. The reinforcement can be applied to the sand-filled embankment with cover layer to solve the complicated problems such as irregular settlement caused by poor stability of the embankment. At present, the research on the sand-filled embankment with cover layer mainly focuses on the sand properties, construction technology, and slope stability, and there are few studies in the experimental field, the deformation characteristics and stability of reinforced sand-filled embankment need further study. In addition, experimental research is relatively rare when the cyclic load is considered in tests. A subgrade structure of geogrid-reinforced sand-filled embankment with cover layer was proposed. The mechanical characteristics, the deformation properties, reinforced behavior and the ultimate bearing capacity of the embankment structure under cyclic loading were studied. For this structure, the geogrids in the sand and the tipping soil are through the geotextile which is arranged in sections continuously so that the geogrids can cross horizontally. Then, the Unsaturated/saturated Soil Triaxial Test System of Geotechnical Consulting and Testing Systems (GCTS), USA was modified to form the loading device of this test, and strain collector was used to measuring deformation and earth pressure of the embankment. A series of cyclic loading model tests were conducted on the geogrid-reinforced sand-filled embankment with a cover layer under a different number of reinforcement layers, the length of reinforcement and thickness of the cover layer. The settlement of the embankment, the normal cumulative deformation of the slope and the earth pressure were studied under different conditions. Besides cyclic loading model tests, model experiments of embankment subjected cyclic-static loading was carried out to analyze ultimate bearing capacity with different loading. The experiment results showed that the vertical cumulative settlement under long-term cyclic loading increases with the decrease of the number of reinforcement layers, length of the reinforcement arrangement and thickness of the tipping soil. Meanwhile, these three factors also have an influence on the decrease of the normal deformation of the embankment slope. The earth pressure around the loading point is significantly affected by putting geogrid in a model embankment. After cyclic loading, the decline of ultimate bearing capacity of the reinforced embankment can be effectively reduced, which is contrary to the unreinforced embankment.

Keywords: cyclic load; geogrid; reinforcement behavior; cumulative deformation; earth pressure

Procedia PDF Downloads 122
38 An Automated Magnetic Dispersive Solid-Phase Extraction Method for Detection of Cocaine in Human Urine

Authors: Feiyu Yang, Chunfang Ni, Rong Wang, Yun Zou, Wenbin Liu, Chenggong Zhang, Fenjin Sun, Chun Wang

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Cocaine is the most frequently used illegal drug globally, with the global annual prevalence of cocaine used ranging from 0.3% to 0.4 % of the adult population aged 15–64 years. Growing consumption trend of abused cocaine and drug crimes are a great concern, therefore urine sample testing has become an important noninvasive sampling whereas cocaine and its metabolites (COCs) are usually present in high concentrations and relatively long detection windows. However, direct analysis of urine samples is not feasible because urine complex medium often causes low sensitivity and selectivity of the determination. On the other hand, presence of low doses of analytes in urine makes an extraction and pretreatment step important before determination. Especially, in gathered taking drug cases, the pretreatment step becomes more tedious and time-consuming. So developing a sensitive, rapid and high-throughput method for detection of COCs in human body is indispensable for law enforcement officers, treatment specialists and health officials. In this work, a new automated magnetic dispersive solid-phase extraction (MDSPE) sampling method followed by high performance liquid chromatography-mass spectrometry (HPLC-MS) was developed for quantitative enrichment of COCs from human urine, using prepared magnetic nanoparticles as absorbants. The nanoparticles were prepared by silanizing magnetic Fe3O4 nanoparticles and modifying them with divinyl benzene and vinyl pyrrolidone, which possesses the ability for specific adsorption of COCs. And this kind of magnetic particle facilitated the pretreatment steps by electromagnetically controlled extraction to achieve full automation. The proposed device significantly improved the sampling preparation efficiency with 32 samples in one batch within 40mins. Optimization of the preparation procedure for the magnetic nanoparticles was explored and the performances of magnetic nanoparticles were characterized by scanning electron microscopy, vibrating sample magnetometer and infrared spectra measurements. Several analytical experimental parameters were studied, including amount of particles, adsorption time, elution solvent, extraction and desorption kinetics, and the verification of the proposed method was accomplished. The limits of detection for the cocaine and cocaine metabolites were 0.09-1.1 ng·mL-1 with recoveries ranging from 75.1 to 105.7%. Compared to traditional sampling method, this method is time-saving and environmentally friendly. It was confirmed that the proposed automated method was a kind of highly effective way for the trace cocaine and cocaine metabolites analyses in human urine.

Keywords: automatic magnetic dispersive solid-phase extraction, cocaine detection, magnetic nanoparticles, urine sample testing

Procedia PDF Downloads 204
37 p-Type Multilayer MoS₂ Enabled by Plasma Doping for Ultraviolet Photodetectors Application

Authors: Xiao-Mei Zhang, Sian-Hong Tseng, Ming-Yen Lu

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Two-dimensional (2D) transition metal dichalcogenides (TMDCs), such as MoS₂, have attracted considerable attention owing to the unique optical and electronic properties related to its 2D ultrathin atomic layer structure. MoS₂ is becoming prevalent in post-silicon digital electronics and in highly efficient optoelectronics due to its extremely low thickness and its tunable band gap (Eg = 1-2 eV). For low-power, high-performance complementary logic applications, both p- and n-type MoS₂ FETs (NFETs and PFETs) must be developed. NFETs with an electron accumulation channel can be obtained using unintentionally doped n-type MoS₂. However, the fabrication of MoS₂ FETs with complementary p-type characteristics is challenging due to the significant difficulty of injecting holes into its inversion channel. Plasma treatments with different species (including CF₄, SF₆, O₂, and CHF₃) have also been found to achieve the desired property modifications of MoS₂. In this work, we demonstrated a p-type multilayer MoS₂ enabled by selective-area doping using CHF₃ plasma treatment. Compared with single layer MoS₂, multilayer MoS₂ can carry a higher drive current due to its lower bandgap and multiple conduction channels. Moreover, it has three times the density of states at its minimum conduction band. Large-area growth of MoS₂ films on 300 nm thick SiO₂/Si substrate is carried out by thermal decomposition of ammonium tetrathiomolybdate, (NH₄)₂MoS₄, in a tube furnace. A two-step annealing process is conducted to synthesize MoS₂ films. For the first step, the temperature is set to 280 °C for 30 min in an N₂ rich environment at 1.8 Torr. This is done to transform (NH₄)₂MoS₄ into MoS₃. To further reduce MoS₃ into MoS₂, the second step of annealing is performed. For the second step, the temperature is set to 750 °C for 30 min in a reducing atmosphere consisting of 90% Ar and 10% H₂ at 1.8 Torr. The grown MoS₂ films are subjected to out-of-plane doping by CHF₃ plasma treatment using a Dry-etching system (ULVAC original NLD-570). The radiofrequency power of this dry-etching system is set to 100 W and the pressure is set to 7.5 mTorr. The final thickness of the treated samples is obtained by etching for 30 s. Back-gated MoS₂ PFETs were presented with an on/off current ratio in the order of 10³ and a field-effect mobility of 65.2 cm²V⁻¹s⁻¹. The MoS₂ PFETs photodetector exhibited ultraviolet (UV) photodetection capability with a rapid response time of 37 ms and exhibited modulation of the generated photocurrent by back-gate voltage. This work suggests the potential application of the mild plasma-doped p-type multilayer MoS₂ in UV photodetectors for environmental monitoring, human health monitoring, and biological analysis.

Keywords: photodetection, p-type doping, multilayers, MoS₂

Procedia PDF Downloads 104
36 Chinese Acupuncture: A Potential Treatment for Autism Rat Model via Improving Synaptic Function

Authors: Sijie Chen, Xiaofang Chen, Juan Wang, Yingying Zhang, Yu Hong, Wanyu Zhuang, Xinxin Huang, Ping Ou, Longsheng Huang

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Purpose: Autistic symptom improvement can be observed in children treated with acupuncture, but the mechanism is still being explored. In the present study, we used scalp acupuncture to treat autism rat model, and then their improvement in the abnormal behaviors and specific mechanisms behind were revealed by detecting animal behaviors, analyzing the RNA sequencing of the prefrontal cortex(PFC), and observing the ultrastructure of PFC neurons under the transmission electron microscope. Methods: On gestational day 12.5, Wistar rats were given valproic acid (VPA) by intraperitoneal injection, and their offspring were considered to be reliable rat models of autism. They were randomized to VPA or VPA-acupuncture group (n=8). Offspring of Wistar pregnant rats that were simultaneously injected with saline were randomly selected as the wild-type group (WT). VPA_acupuncture group rats received acupuncture intervention at 23 days of age for 4 weeks, and the other two groups followed without intervention. After the intervention, all experimental rats underwent behavioral tests. Immediately afterward, they were euthanized by cervical dislocation, and their prefrontal cortex was isolated for RNA sequencing and transmission electron microscopy. Results: The main results are as follows: 1. Animal behavioural tests: VPA group rats showed more anxiety-like behaviour and repetitive, stereotyped behaviour than WT group rats. While VPA group rats showed less spatial exploration ability, activity level, social interaction, and social novelty preference than WT group rats. It was gratifying to observe that acupuncture indeed improved these abnormal behaviors of autism rat model. 2. RNA-sequencing: The three groups of rats differed in the expression and enrichment pathways of multiple genes related to synaptic function, neural signal transduction, and circadian rhythm regulation. Our experiments indicated that acupuncture can alleviate the major symptoms of ASD by improving these neurological abnormalities. 3. Under the transmission electron microscopy, several lysosomes and mitochondrial structural abnormalities were observed in the prefrontal neurons of VPA group rats, which were manifested as atrophy of the mitochondrial membran, blurring or disappearance of the mitochondrial cristae, and even vacuolization. Moreover, the number of synapses and synaptic vesicles was relatively small. Conversely, the mitochondrial structure of rats in the WT group and VPA_acupuncture was normal, and the number of synapses and synaptic vesicles was relatively large. Conclusion: Acupuncture effectively improved the abnormal behaviors of autism rat model and the ultrastructure of the PFC neurons, which might worked by improving their abnormal synaptic function, synaptic plasticity and promoting neuronal signal transduction.

Keywords: autism spectrum disorder, acupuncture, animal behavior, RNA sequencing, transmission electron microscope

Procedia PDF Downloads 46
35 Electrical Degradation of GaN-based p-channel HFETs Under Dynamic Electrical Stress

Authors: Xuerui Niu, Bolin Wang, Xinchuang Zhang, Xiaohua Ma, Bin Hou, Ling Yang

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The application of discrete GaN-based power switches requires the collaboration of silicon-based peripheral circuit structures. However, the packages and interconnection between the Si and GaN devices can introduce parasitic effects to the circuit, which has great impacts on GaN power transistors. GaN-based monolithic power integration technology is an emerging solution which can improve the stability of circuits and allow the GaN-based devices to achieve more functions. Complementary logic circuits consisting of GaN-based E-mode p-channel heterostructure field-effect transistors (p-HFETs) and E-mode n-channel HEMTs can be served as the gate drivers. E-mode p-HFETs with recessed gate have attracted increasing interest because of the low leakage current and large gate swing. However, they suffer from a poor interface between the gate dielectric and polarized nitride layers. The reliability of p-HFETs is analyzed and discussed in this work. In circuit applications, the inverter is always operated with dynamic gate voltage (VGS) rather than a constant VGS. Therefore, dynamic electrical stress has been simulated to resemble the operation conditions for E-mode p-HFETs. The dynamic electrical stress condition is as follows. VGS is a square waveform switching from -5 V to 0 V, VDS is fixed, and the source grounded. The frequency of the square waveform is 100kHz with the rising/falling time of 100 ns and duty ratio of 50%. The effective stress time is 1000s. A number of stress tests are carried out. The stress was briefly interrupted to measure the linear IDS-VGS, saturation IDS-VGS, As VGS switches from -5 V to 0 V and VDS = 0 V, devices are under negative-bias-instability (NBI) condition. Holes are trapped at the interface of oxide layer and GaN channel layer, which results in the reduction of VTH. The negative shift of VTH is serious at the first 10s and then changes slightly with the following stress time. However, different phenomenon is observed when VDS reduces to -5V. VTH shifts negatively during stress condition, and the variation in VTH increases with time, which is different from that when VDS is 0V. Two mechanisms exists in this condition. On the one hand, the electric field in the gate region is influenced by the drain voltage, so that the trapping behavior of holes in the gate region changes. The impact of the gate voltage is weakened. On the other hand, large drain voltage can induce the hot holes generation and lead to serious hot carrier stress (HCS) degradation with time. The poor-quality interface between the oxide layer and GaN channel layer at the gate region makes a major contribution to the high-density interface traps, which will greatly influence the reliability of devices. These results emphasize that the improved etching and pretreatment processes needs to be developed so that high-performance GaN complementary logics with enhanced stability can be achieved.

Keywords: GaN-based E-mode p-HFETs, dynamic electric stress, threshold voltage, monolithic power integration technology

Procedia PDF Downloads 94
34 Probabilistic Study of Impact Threat to Civil Aircraft and Realistic Impact Energy

Authors: Ye Zhang, Chuanjun Liu

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In-service aircraft is exposed to different types of threaten, e.g. bird strike, ground vehicle impact, and run-way debris, or even lightning strike, etc. To satisfy the aircraft damage tolerance design requirements, the designer has to understand the threatening level for different types of the aircraft structures, either metallic or composite. Exposing to low-velocity impacts may produce very serious internal damages such as delaminations and matrix cracks without leaving visible mark onto the impacted surfaces for composite structures. This internal damage can cause significant reduction in the load carrying capacity of structures. The semi-probabilistic method provides a practical and proper approximation to establish the impact-threat based energy cut-off level for the damage tolerance evaluation of the aircraft components. Thus, the probabilistic distribution of impact threat and the realistic impact energy level cut-offs are the essential establishments required for the certification of aircraft composite structures. A new survey of impact threat to civil aircraft in-service has recently been carried out based on field records concerning around 500 civil aircrafts (mainly single aisles) and more than 4.8 million flight hours. In total 1,006 damages caused by low-velocity impact events had been screened out from more than 8,000 records including impact dents, scratches, corrosions, delaminations, cracks etc. The impact threat dependency on the location of the aircraft structures and structural configuration was analyzed. Although the survey was mainly focusing on the metallic structures, the resulting low-energy impact data are believed likely representative to general civil aircraft, since the service environments and the maintenance operations are independent of the materials of the structures. The probability of impact damage occurrence (Po) and impact energy exceedance (Pe) are the two key parameters for describing the statistic distribution of impact threat. With the impact damage events from the survey, Po can be estimated as 2.1x10-4 per flight hour. Concerning the calculation of Pe, a numerical model was developed using the commercial FEA software ABAQUS to backward estimate the impact energy based on the visible damage characteristics. The relationship between the visible dent depth and impact energy was established and validated by drop-weight impact experiments. Based on survey results, Pe was calculated and assumed having a log-linear relationship versus the impact energy. As the product of two aforementioned probabilities, Po and Pe, it is reasonable and conservative to assume Pa=PoxPe=10-5, which indicates that the low-velocity impact events are similarly likely as the Limit Load events. Combing Pa with two probabilities Po and Pe obtained based on the field survey, the cutoff level of realistic impact energy was estimated and valued as 34 J. In summary, a new survey was recently done on field records of civil aircraft to investigate the probabilistic distribution of impact threat. Based on the data, two probabilities, Po and Pe, were obtained. Considering a conservative assumption of Pa, the cutoff energy level for the realistic impact energy has been determined, which provides potential applicability in damage tolerance certification of future civil aircraft.

Keywords: composite structure, damage tolerance, impact threat, probabilistic

Procedia PDF Downloads 308
33 Coordinative Remote Sensing Observation Technology for a High Altitude Barrier Lake

Authors: Zhang Xin

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Barrier lakes are lakes formed by storing water in valleys, river valleys or riverbeds after being blocked by landslide, earthquake, debris flow, and other factors. They have great potential safety hazards. When the water is stored to a certain extent, it may burst in case of strong earthquake or rainstorm, and the lake water overflows, resulting in large-scale flood disasters. In order to ensure the safety of people's lives and property in the downstream, it is very necessary to monitor the barrier lake. However, it is very difficult and time-consuming to manually monitor the barrier lake in high altitude areas due to the harsh climate and steep terrain. With the development of earth observation technology, remote sensing monitoring has become one of the main ways to obtain observation data. Compared with a single satellite, multi-satellite remote sensing cooperative observation has more advantages; its spatial coverage is extensive, observation time is continuous, imaging types and bands are abundant, it can monitor and respond quickly to emergencies, and complete complex monitoring tasks. Monitoring with multi-temporal and multi-platform remote sensing satellites can obtain a variety of observation data in time, acquire key information such as water level and water storage capacity of the barrier lake, scientifically judge the situation of the barrier lake and reasonably predict its future development trend. In this study, The Sarez Lake, which formed on February 18, 1911, in the central part of the Pamir as a result of blockage of the Murgab River valley by a landslide triggered by a strong earthquake with magnitude of 7.4 and intensity of 9, is selected as the research area. Since the formation of Lake Sarez, it has aroused widespread international concern about its safety. At present, the use of mechanical methods in the international analysis of the safety of Lake Sarez is more common, and remote sensing methods are seldom used. This study combines remote sensing data with field observation data, and uses the 'space-air-ground' joint observation technology to study the changes in water level and water storage capacity of Lake Sarez in recent decades, and evaluate its safety. The situation of the collapse is simulated, and the future development trend of Lake Sarez is predicted. The results show that: 1) in recent decades, the water level of Lake Sarez has not changed much and remained at a stable level; 2) unless there is a strong earthquake or heavy rain, it is less likely that the Lake Sarez will be broken under normal conditions, 3) lake Sarez will remain stable in the future, but it is necessary to establish an early warning system in the Lake Sarez area for remote sensing of the area, 4) the coordinative remote sensing observation technology is feasible for the high altitude barrier lake of Sarez.

Keywords: coordinative observation, disaster, remote sensing, geographic information system, GIS

Procedia PDF Downloads 128
32 Examining the Drivers of Engagement in Social Media Brand Communities

Authors: Rania S. Hussein

Abstract:

This research mainly focuses on examining engagement in social media brand communities. Engagement in social media has become a main focus in literature affirming that the role of social media in our daily lives is growing. (Akman and Mishra, 2017;Prado-Gascó et al., 2017). Social media has also become a key medium for brand communication and brand building relationships(Frimpong and McLean,2018;Dimitriu and Guesalaga, 2017). Engagement on social media has become a main focus of many researchers who tried to understand this concept further and draw a link between engagement and various social media activities (Cvijikj and Michahelles;2013), Andre,2015; Wang et al., 2015). According to Felix et al. (2017), the internet and social media have provided better digital resources to improve brand loyalty and customer interactions, thus leading to social media engagement within brand communities. The aim of this research is to highlight the importance of social media and why it is important to maintain engagement within social media. While the term ‘engagement’ is widely used in scholarly literature, there isn’t a common consensus about what the term exactly entails, according to Kidd, (2011). On one hand, it was seen as something that includes factors such as participation, activation, empowerment, devotion, trust, and productivity (Zhang et al, andBenyoucef, M. (2016), ). Other scholars held different viewpoints. For example, Lim et al. (2015) has chosen to break down engagement into three types: operational engagement, emotional engagement, and relational engagement. Chandler and Lusch (2015) further studied engagement as a means to measure commitment to a brand. Fernandes&Remelhe (2016) had a more technical view, measuring engagement through comments, following, subscribing, sharing, enjoying, writing, etc., in the social media context. ustomer engagement has become a research focus for understanding how consumer relationships are developed, retained, and improved within a digital context. Based on previous literature, it is evident that many customer engagement related studies are limited to the interaction between firms and consumers on social media. There is a clear gap in the literature regarding consumer-to-consumer interaction and user-generated content and its significance. While some researchers, such as Alversia et al. (2016), touched upon the importance of customer-based engagement, a gap still remains: there is no consistent and well-tested method for defining the factors that affect consumer interaction. Moreover, few scholarly research papers such as (Case, 2019; Riley, 2020;Habibi, 2014) provided to assist businesses understand their customers' interaction habits as well as the best ways to develop customer loyalty. Additionally, the majority of research on brand pages concentrated on the drivers of Consumer engagement, with just a few studies example, Lamberton, Cc(2016), Poorrezaei, (2016). (Jayasingh, 2019), looking into the implications. This study focuses on understanding the concept of engagement and its importance, specifically engagement within social media brand communities. It examines drivers as well as consequences of engagement, including brand knowledge, brand trust, entertainment, and brand page interactivity. Brand engagement is also expected to affect brand loyalty and word of the mouth.

Keywords: engagement, social media, brand communities, drivers

Procedia PDF Downloads 163
31 An Introduction to the Radiation-Thrust Based on Alpha Decay and Spontaneous Fission

Authors: Shiyi He, Yan Xia, Xiaoping Ouyang, Liang Chen, Zhongbing Zhang, Jinlu Ruan

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As the key system of the spacecraft, various propelling system have been developing rapidly, including ion thrust, laser thrust, solar sail and other micro-thrusters. However, there still are some shortages in these systems. The ion thruster requires the high-voltage or magnetic field to accelerate, resulting in extra system, heavy quantity and large volume. The laser thrust now is mostly ground-based and providing pulse thrust, restraint by the station distribution and the capacity of laser. The thrust direction of solar sail is limited to its relative position with the Sun, so it is hard to propel toward the Sun or adjust in the shadow.In this paper, a novel nuclear thruster based on alpha decay and spontaneous fission is proposed and the principle of this radiation-thrust with alpha particle has been expounded. Radioactive materials with different released energy, such as 210Po with 5.4MeV and 238Pu with 5.29MeV, attached to a metal film will provides various thrust among 0.02-5uN/cm2. With this repulsive force, radiation is able to be a power source. With the advantages of low system quantity, high accuracy and long active time, the radiation thrust is promising in the field of space debris removal, orbit control of nano-satellite array and deep space exploration. To do further study, a formula lead to the amplitude and direction of thrust by the released energy and decay coefficient is set up. With the initial formula, the alpha radiation elements with the half life period longer than a hundred days are calculated and listed. As the alpha particles emit continuously, the residual charge in metal film grows and affects the emitting energy distribution of alpha particles. With the residual charge or extra electromagnetic field, the emitting of alpha particles performs differently and is analyzed in this paper. Furthermore, three more complex situations are discussed. Radiation element generating alpha particles with several energies in different intensity, mixture of various radiation elements, and cascaded alpha decay are studied respectively. In combined way, it is more efficient and flexible to adjust the thrust amplitude. The propelling model of the spontaneous fission is similar with the one of alpha decay, which has a more complex angular distribution. A new quasi-sphere space propelling system based on the radiation-thrust has been introduced, as well as the collecting and processing system of excess charge and reaction heat. The energy and spatial angular distribution of emitting alpha particles on unit area and certain propelling system have been studied. As the alpha particles are easily losing energy and self-absorb, the distribution is not the simple stacking of each nuclide. With the change of the amplitude and angel of radiation-thrust, orbital variation strategy on space debris removal is shown and optimized.

Keywords: alpha decay, angular distribution, emitting energy, orbital variation, radiation-thruster

Procedia PDF Downloads 209
30 Developing Granular Sludge and Maintaining High Nitrite Accumulation for Anammox to Treat Municipal Wastewater High-efficiently in a Flexible Two-stage Process

Authors: Zhihao Peng, Qiong Zhang, Xiyao Li, Yongzhen Peng

Abstract:

Nowadays, conventional nitrogen removal process (nitrification and denitrification) was adopted in most wastewater treatment plants, but many problems have occurred, such as: high aeration energy consumption, extra carbon sources dosage and high sludge treatment costs. The emergence of anammox has bring about the great revolution to the nitrogen removal technology, and only the ammonia and nitrite were required to remove nitrogen autotrophically, no demand for aeration and sludge treatment. However, there existed many challenges in anammox applications: difficulty of biomass retention, insufficiency of nitrite substrate, damage from complex organic etc. Much effort was put into the research in overcoming the above challenges, and the payment was rewarded. It was also imperative to establish an innovative process that can settle the above problems synchronously, after all any obstacle above mentioned can cause the collapse of anammox system. Therefore, in this study, a two-stage process was established that the sequencing batch reactor (SBR) and upflow anaerobic sludge blanket (UASB) were used in the pre-stage and post-stage, respectively. The domestic wastewater entered into the SBR first and went through anaerobic/aerobic/anoxic (An/O/A) mode, and the draining at the aerobic end of SBR was mixed with domestic wastewater, the mixture then entering to the UASB. In the long term, organic and nitrogen removal performance was evaluated. All along the operation, most COD was removed in pre-stage (COD removal efficiency > 64.1%), including some macromolecular organic matter, like: tryptophan, tyrosinase and fulvic acid, which could weaken the damage of organic matter to anammox. And the An/O/A operating mode of SBR was beneficial to the achievement and maintenance of partial nitrification (PN). Hence, sufficient and steady nitrite supply was another favorable condition to anammox enhancement. Besides, the flexible mixing ratio helped to gain a substrate ratio appropriate to anammox (1.32-1.46), which further enhance the anammox. Further, the UASB was used and gas recirculation strategy was adopted in the post-stage, aiming to achieve granulation by the selection pressure. As expected, the granules formed rapidly during 38 days, which increased from 153.3 to 354.3 μm. Based on bioactivity and gene measurement, the anammox metabolism and abundance level rose evidently, by 2.35 mgN/gVss·h and 5.3 x109. The anammox bacteria mainly distributed in the large granules (>1000 μm), while the biomass in the flocs (<200 μm) and microgranules (200-500 μm) barely displayed anammox bioactivity. Enhanced anammox promoted the advanced autotrophic nitrogen removal, which increased from 71.9% to 93.4%, even when the temperature was only 12.9 ℃. Therefore, it was feasible to enhance anammox in the multiple favorable conditions created, and the strategy extended the application of anammox to the full-scale mainstream, enhanced the understanding of anammox in the aspects of culturing conditions.

Keywords: anammox, granules, nitrite accumulation, nitrogen removal efficiency

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29 A Smart Sensor Network Approach Using Affordable River Water Level Sensors

Authors: Dian Zhang, Brendan Heery, Maria O’Neill, Ciprian Briciu-Burghina, Noel E. O’Connor, Fiona Regan

Abstract:

Recent developments in sensors, wireless data communication and the cloud computing have brought the sensor web to a whole new generation. The introduction of the concept of ‘Internet of Thing (IoT)’ has brought the sensor research into a new level, which involves the developing of long lasting, low cost, environment friendly and smart sensors; new wireless data communication technologies; big data analytics algorithms and cloud based solutions that are tailored to large scale smart sensor network. The next generation of smart sensor network consists of several layers: physical layer, where all the smart sensors resident and data pre-processes occur, either on the sensor itself or field gateway; data transmission layer, where data and instructions exchanges happen; the data process layer, where meaningful information is extracted and organized from the pre-process data stream. There are many definitions of smart sensor, however, to summarize all these definitions, a smart sensor must be Intelligent and Adaptable. In future large scale sensor network, collected data are far too large for traditional applications to send, store or process. The sensor unit must be intelligent that pre-processes collected data locally on board (this process may occur on field gateway depends on the sensor network structure). In this case study, three smart sensing methods, corresponding to simple thresholding, statistical model and machine learning based MoPBAS method, are introduced and their strength and weakness are discussed as an introduction to the smart sensing concept. Data fusion, the integration of data and knowledge from multiple sources, are key components of the next generation smart sensor network. For example, in the water level monitoring system, weather forecast can be extracted from external sources and if a heavy rainfall is expected, the server can send instructions to the sensor notes to, for instance, increase the sampling rate or switch on the sleeping mode vice versa. In this paper, we describe the deployment of 11 affordable water level sensors in the Dublin catchment. The objective of this paper is to use the deployed river level sensor network at the Dodder catchment in Dublin, Ireland as a case study to give a vision of the next generation of a smart sensor network for flood monitoring to assist agencies in making decisions about deploying resources in the case of a severe flood event. Some of the deployed sensors are located alongside traditional water level sensors for validation purposes. Using the 11 deployed river level sensors in a network as a case study, a vision of the next generation of smart sensor network is proposed. Each key component of the smart sensor network is discussed, which hopefully inspires the researchers who are working in the sensor research domain.

Keywords: smart sensing, internet of things, water level sensor, flooding

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28 Safety and Efficacy of RM-001, Autologous HBG1/2 Promoter-Modified CD34+Hematopoietic Stem and Progenitor Cells, in Transfusion-Dependent β-Thalassemia

Authors: Rongrong Liu, Li Wang, Hui Xu, Jianpei Fang, Sixi Liu, Xiaolin Yin, Junbin Liang, Gaohui Yan, Yaoyun Li, Yali Zhou, Xinyu Li, Yue Li, Lei Shi, Yongrong Lai, Junjiu Huang, Xinhua Zhang

Abstract:

Background: Beta-Thalassemia is caused by reduced (β+) or absent (β0) synthesis of the β-globin chains of hemoglobin. Transfusions and oral iron chelation therapy have improved the quality of life for patients with Transfusion-Dependent thalassemia (TDT). Recent advances in genome editing platforms of CRISPR-Cas9 have paved the way for induction of HbF by reactivating expression of γ-chain.Aims: We performed CRISPR-Cas9-mediated genome editing of hematopoietic stem cells to mutate HBG1/HBG2 promoter sequence, thereby representing a naturally occurring HPFH-liked mutation, producing RM-001. Here, we present an initial assessment of safety and efficacy of RM-001 in patients with TDT. Methods: Patients (6–35 y of age) with TDT receiving packed red blood cell (pRBC) transfusions of ≥100 mL/kg/y or ≥10 units/y in the previous 2 y were eligible. CD34+ cells were edited with CRISPR-Cas9 using a guide RNA specific for the binding site of BCL11A on the HBG1/2 promoter. Prior to RM-001 product infusion (day 0), patients received myeloablative conditioning with Busulfan from day-7 to day-4. Patients were monitored for AEs Hb expression.Results: Data cut as of 28 Feb 2024, 16 TDT patients have been treated with RM-001 and followed ≥3 months. 5 of these 16 patients had finished their 24 months follow up. Eleven patients have β0/β0 genotype and five patients have β0/β+ genotype. In addition to β-thalassemia, two patients had α- deletion with the genotype of --/αα. Efficacy:All patients received a single dose intravenous infusion of RM-001 cells. 5 of them had been followed 24 months or longer. All patients achieved transfusion-independent (TI, total Hb continued ≥ 9g/dL) (Figure1). Patients demonstrated sustained and clinically meaningful increases in HbF levels since 4 month post-RM-001 infusion (Figure.2). Total hemoglobin in all patients was stable at 10-12g/dL during the follow-up period. Safety:The adverse events observed after RM-001 infusion were consistent with those that are typical of Busulfan-based myeloablation. The allelic editing analysis at 6-month visit showed that the on-target allelic editing frequency in bone marrow cells was 73.44% (64.65% to 84.6%, n=13).Summary/Conclusion: This interim analysis, in which all the 19 patients age from 7.9 to 25yo met the success criteria for the trial with respect to transfusion independence, showed that autologous HBG1/2 promoter-modified CD34+ HSPCs gene therapy resulted in an adequate amount of HbF as early as 2 months after infusion led to near-normal hemoglobin levels, remained transfusion-free through the reported period without product related SAE. After RM-001 infusion, high levels of HbF proportion and on-target editing in bone marrow cells were maintained. Submitted on behalf of the RM-001 Investigators.

Keywords: thalassemian, genetherapy, CRISPR/Cas9, HbF

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27 Integrated Care on Chronic Diseases in Asia-Pacific Countries

Authors: Chang Liu, Hanwen Zhang, Vikash Sharma, Don Eliseo Lucerno-Prisno III, Emmanuel Yujuico, Maulik Chokshi, Prashanthi Krishnakumar, Bach Xuan Tran, Giang Thu Vu, Kamilla Anna Pinter, Shenglan Tang

Abstract:

Background and Aims: Globally, many health systems focus on hospital-based healthcare models targeting acute care and disease treatment, which are not effective in addressing the challenges of ageing populations, chronic conditions, multi-morbidities, and increasingly unhealthy lifestyles. Recently, integrated care programs on chronic diseases have been developed, piloted, and implemented to meet such challenges. However, integrated care programs in the Asia-Pacific region vary in the levels of integration from linkage to coordination to full integration. This study aims to identify and analyze existing cases of integrated care in the Asia-Pacific region and identify the facilitators and barriers in order to improve existing cases and inform future cases. Methods: The study is a comparative study, with a combination approach of desk-based research and key informant interviews. The selected countries included in this study represent a good mix of lower-middle income countries (the Philippines, India, Vietnam, and Fiji), upper-middle income country (China), and high-income country (Singapore) in the Asia-Pacific region. Existing integrated care programs were identified through the scoping review approach. Trigger, history, general design, beneficiaries, and objectors were summarized with barriers and facilitators of integrated care based on key informant interviews. Representative case(s) in each country were selected and comprehensively analyzed through deep-dive case studies. Results: A total of 87 existing integrated care programs on chronic diseases were found in all countries, with 44 in China, 21 in Singapore, 12 in India, 5 in Vietnam, 4 in the Philippines, and 1 in Fiji. 9 representative cases of integrated care were selected for in-depth description and analysis, with 2 in China, the Philippines, and Vietnam, and 1 in Singapore, India, and Fiji. Population aging and the rising chronic disease burden have been identified as key drivers for almost all the six countries. Among the six countries, Singapore has the longest history of integrated care, followed by Fiji, the Philippines, and China, while India and Vietnam have a shorter history of integrated care. Incentives, technologies, education, and performance evaluation would be crucial for developing strategies for implementing future programs and improve already existing programs. Conclusion: Integrated care is important for addressing challenges surrounding the delivery of long-term care. To date, there is an increasing trend of integrated care programs on chronic diseases in the Asia-Pacific region, and all six countries in our study set integrated care as a direction for their health systems transformation.

Keywords: integrated healthcare, integrated care delivery, chronic diseases, Asia-Pacific region

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26 Identification of Hub Genes in the Development of Atherosclerosis

Authors: Jie Lin, Yiwen Pan, Li Zhang, Zhangyong Xia

Abstract:

Atherosclerosis is a chronic inflammatory disease characterized by the accumulation of lipids, immune cells, and extracellular matrix in the arterial walls. This pathological process can lead to the formation of plaques that can obstruct blood flow and trigger various cardiovascular diseases such as heart attack and stroke. The underlying molecular mechanisms still remain unclear, although many studies revealed the dysfunction of endothelial cells, recruitment and activation of monocytes and macrophages, and the production of pro-inflammatory cytokines and chemokines in atherosclerosis. This study aimed to identify hub genes involved in the progression of atherosclerosis and to analyze their biological function in silico, thereby enhancing our understanding of the disease’s molecular mechanisms. Through the analysis of microarray data, we examined the gene expression in media and neo-intima from plaques, as well as distant macroscopically intact tissue, across a cohort of 32 hypertensive patients. Initially, 112 differentially expressed genes (DEGs) were identified. Subsequent immune infiltration analysis indicated a predominant presence of 27 immune cell types in the atherosclerosis group, particularly noting an increase in monocytes and macrophages. In the Weighted gene co-expression network analysis (WGCNA), 10 modules with a minimum of 30 genes were defined as key modules, with blue, dark, Oliver green and sky-blue modules being the most significant. These modules corresponded respectively to monocyte, activated B cell, and activated CD4 T cell gene patterns, revealing a strong morphological-genetic correlation. From these three gene patterns (modules morphology), a total of 2509 key genes (Gene Significance >0.2, module membership>0.8) were extracted. Six hub genes (CD36, DPP4, HMOX1, PLA2G7, PLN2, and ACADL) were then identified by intersecting 2509 key genes, 102 DEGs with lipid-related genes from the Genecard database. The bio-functional analysis of six hub genes was estimated by a robust classifier with an area under the curve (AUC) of 0.873 in the ROC plot, indicating excellent efficacy in differentiating between the disease and control group. Moreover, PCA visualization demonstrated clear separation between the groups based on these six hub genes, suggesting their potential utility as classification features in predictive models. Protein-protein interaction (PPI) analysis highlighted DPP4 as the most interconnected gene. Within the constructed key gene-drug network, 462 drugs were predicted, with ursodeoxycholic acid (UDCA) being identified as a potential therapeutic agent for modulating DPP4 expression. In summary, our study identified critical hub genes implicated in the progression of atherosclerosis through comprehensive bioinformatic analyses. These findings not only advance our understanding of the disease but also pave the way for applying similar analytical frameworks and predictive models to other diseases, thereby broadening the potential for clinical applications and therapeutic discoveries.

Keywords: atherosclerosis, hub genes, drug prediction, bioinformatics

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