Search results for: brain cooling
Commenced in January 2007
Frequency: Monthly
Edition: International
Paper Count: 2094

Search results for: brain cooling

1134 Intelligent Materials and Functional Aspects of Shape Memory Alloys

Authors: Osman Adiguzel

Abstract:

Shape-memory alloys are a new class of functional materials with a peculiar property known as shape memory effect. These alloys return to a previously defined shape on heating after deformation in low temperature product phase region and take place in a class of functional materials due to this property. The origin of this phenomenon lies in the fact that the material changes its internal crystalline structure with changing temperature. Shape memory effect is based on martensitic transitions, which govern the remarkable changes in internal crystalline structure of materials. Martensitic transformation, which is a solid state phase transformation, occurs in thermal manner in material on cooling from high temperature parent phase region. This transformation is governed by changes in the crystalline structure of the material. Shape memory alloys cycle between original and deformed shapes in bulk level on heating and cooling, and can be used as a thermal actuator or temperature-sensitive elements due to this property. Martensitic transformations usually occur with the cooperative movement of atoms by means of lattice invariant shears. The ordered parent phase structures turn into twinned structures with this movement in crystallographic manner in thermal induced case. The twinned martensites turn into the twinned or oriented martensite by stressing the material at low temperature martensitic phase condition. The detwinned martensite turns into the parent phase structure on first heating, first cycle, and parent phase structures turn into the twinned and detwinned structures respectively in irreversible and reversible memory cases. On the other hand, shape memory materials are very important and useful in many interdisciplinary fields such as medicine, pharmacy, bioengineering, metallurgy and many engineering fields. The choice of material as well as actuator and sensor to combine it with the host structure is very essential to develop main materials and structures. Copper based alloys exhibit this property in metastable beta-phase region, which has bcc-based structures at high temperature parent phase field, and these structures martensitically turn into layered complex structures with lattice twinning following two ordered reactions on cooling. Martensitic transition occurs as self-accommodated martensite with inhomogeneous shears, lattice invariant shears which occur in two opposite directions, <110 > -type directions on the {110}-type plane of austenite matrix which is basal plane of martensite. This kind of shear can be called as {110}<110> -type mode and gives rise to the formation of layered structures, like 3R, 9R or 18R depending on the stacking sequences on the close-packed planes of the ordered lattice. In the present contribution, x-ray diffraction and transmission electron microscopy (TEM) studies were carried out on two copper based alloys which have the chemical compositions in weight; Cu-26.1%Zn 4%Al and Cu-11%Al-6%Mn. X-ray diffraction profiles and electron diffraction patterns reveal that both alloys exhibit super lattice reflections inherited from parent phase due to the displacive character of martensitic transformation. X-ray diffractograms taken in a long time interval show that locations and intensities of diffraction peaks change with the aging time at room temperature. In particular, some of the successive peak pairs providing a special relation between Miller indices come close each other.

Keywords: Shape memory effect, martensite, twinning, detwinning, self-accommodation, layered structures

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1133 A Case Report on Cognitive-Communication Intervention in Traumatic Brain Injury

Authors: Nikitha Francis, Anjana Hoode, Vinitha George, Jayashree S. Bhat

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The interaction between cognition and language, referred as cognitive-communication, is very intricate, involving several mental processes such as perception, memory, attention, lexical retrieval, decision making, motor planning, self-monitoring and knowledge. Cognitive-communication disorders are difficulties in communicative competencies that result from underlying cognitive impairments of attention, memory, organization, information processing, problem solving, and executive functions. Traumatic brain injury (TBI) is an acquired, non - progressive condition, resulting in distinct deficits of cognitive communication abilities such as naming, word-finding, self-monitoring, auditory recognition, attention, perception and memory. Cognitive-communication intervention in TBI is individualized, in order to enhance the person’s ability to process and interpret information for better functioning in their family and community life. The present case report illustrates the cognitive-communicative behaviors and the intervention outcomes of an adult with TBI, who was brought to the Department of Audiology and Speech Language Pathology, with cognitive and communicative disturbances, consequent to road traffic accident. On a detailed assessment, she showed naming deficits along with perseverations and had severe difficulty in recalling the details of the accident, her house address, places she had visited earlier, names of people known to her, as well as the activities she did each day, leading to severe breakdowns in her communicative abilities. She had difficulty in initiating, maintaining and following a conversation. She also lacked orientation to time and place. On administration of the Manipal Manual of Cognitive Linguistic Abilities (MMCLA), she exhibited poor performance on tasks related to visual and auditory perception, short term memory, working memory and executive functions. She attended 20 sessions of cognitive-communication intervention which followed a domain-general, adaptive training paradigm, with tasks relevant to everyday cognitive-communication skills. Compensatory strategies such as maintaining a dairy with reminders of her daily routine, names of people, date, time and place was also recommended. MMCLA was re-administered and her performance in the tasks showed significant improvements. Occurrence of perseverations and word retrieval difficulties reduced. She developed interests to initiate her day-to-day activities at home independently, as well as involve herself in conversations with her family members. Though she lacked awareness about her deficits, she actively involved herself in all the therapy activities. Rehabilitation of moderate to severe head injury patients can be done effectively through a holistic cognitive retraining with a focus on different cognitive-linguistic domains. Selection of goals and activities should have relevance to the functional needs of each individual with TBI, as highlighted in the present case report.

Keywords: cognitive-communication, executive functions, memory, traumatic brain injury

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1132 An Investigation of Vegetable Oils as Potential Insulating Liquid

Authors: Celal Kocatepe, Eyup Taslak, Celal Fadil Kumru, Oktay Arikan

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While choosing insulating oil, characteristic features such as thermal cooling, endurance, efficiency and being environment-friendly should be considered. Mineral oils are referred as petroleum-based oil. In this study, vegetable oils investigated as an alternative insulating liquid to mineral oil. Dissipation factor, breakdown voltage, relative dielectric constant and resistivity changes with the frequency and voltage of mineral, rapeseed and nut oils were measured. Experimental studies were performed according to ASTM D924 and IEC 60156 standards.

Keywords: breakdown voltage, dielectric dissipation factor, mineral oil, vegetable oils

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1131 Aerosol Radiative Forcing Over Indian Subcontinent for 2000-2021 Using Satellite Observations

Authors: Shreya Srivastava, Sushovan Ghosh, Sagnik Dey

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Aerosols directly affect Earth’s radiation budget by scattering and absorbing incoming solar radiation and outgoing terrestrial radiation. While the uncertainty in aerosol radiative forcing (ARF) has decreased over the years, it is still higher than that of greenhouse gas forcing, particularly in the South Asian region, due to high heterogeneity in their chemical properties. Understanding the Spatio-temporal heterogeneity of aerosol composition is critical in improving climate prediction. Studies using satellite data, in-situ and aircraft measurements, and models have investigated the Spatio-temporal variability of aerosol characteristics. In this study, we have taken aerosol data from Multi-angle Imaging Spectro-Radiometer (MISR) level-2 version 23 aerosol products retrieved at 4.4 km and radiation data from Clouds and the Earth’s Radiant Energy System (CERES, spatial resolution=1ox1o) for 21 years (2000-2021) over the Indian subcontinent. MISR aerosol product includes size and shapes segregated aerosol optical depth (AOD), Angstrom exponent (AE), and single scattering albedo (SSA). Additionally, 74 aerosol mixtures are included in version 23 data that is used for aerosol speciation. We have seasonally mapped aerosol optical and microphysical properties from MISR for India at quarter degrees resolution. Results show strong Spatio-temporal variability, with a constant higher value of AOD for the Indo-Gangetic Plain (IGP). The contribution of small-size particles is higher throughout the year, spatially during winter months. SSA is found to be overestimated where absorbing particles are present. The climatological map of short wave (SW) ARF at the top of the atmosphere (TOA) shows a strong cooling except in only a few places (values ranging from +2.5o to -22.5o). Cooling due to aerosols is higher in the absence of clouds. Higher negative values of ARF are found over the IGP region, given the high aerosol concentration above the region. Surface ARF values are everywhere negative for our study domain, with higher values in clear conditions. The results strongly correlate with AOD from MISR and ARF from CERES.

Keywords: aerosol Radiative forcing (ARF), aerosol composition, single scattering albedo (SSA), CERES

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1130 Aerosol Direct Radiative Forcing Over the Indian Subcontinent: A Comparative Analysis from the Satellite Observation and Radiative Transfer Model

Authors: Shreya Srivastava, Sagnik Dey

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Aerosol direct radiative forcing (ADRF) refers to the alteration of the Earth's energy balance from the scattering and absorption of solar radiation by aerosol particles. India experiences substantial ADRF due to high aerosol loading from various sources. These aerosols' radiative impact depends on their physical characteristics (such as size, shape, and composition) and atmospheric distribution. Quantifying ADRF is crucial for understanding aerosols’ impact on the regional climate and the Earth's radiative budget. In this study, we have taken radiation data from Clouds and the Earth’s Radiant Energy System (CERES, spatial resolution=1ox1o) for 22 years (2000-2021) over the Indian subcontinent. Except for a few locations, the short-wave DARF exhibits aerosol cooling at the TOA (values ranging from +2.5 W/m2 to -22.5W/m2). Cooling due to aerosols is more pronounced in the absence of clouds. Being an aerosol hotspot, higher negative ADRF is observed over the Indo-Gangetic Plain (IGP). Aerosol Forcing Efficiency (AFE) shows a decreasing seasonal trend in winter (DJF) over the entire study region while an increasing trend over IGP and western south India during the post-monsoon season (SON) in clear-sky conditions. Analysing atmospheric heating and AOD trends, we found that only the aerosol loading is not governing the change in atmospheric heating but also the aerosol composition and/or their vertical profile. We used a Multi-angle Imaging Spectro-Radiometer (MISR) Level-2 Version 23 aerosol products to look into aerosol composition. MISR incorporates 74 aerosol mixtures in its retrieval algorithm based on size, shape, and absorbing properties. This aerosol mixture information was used for analysing long-term changes in aerosol composition and dominating aerosol species corresponding to the aerosol forcing value. Further, ADRF derived from this method is compared with around 35 studies across India, where a plane parallel Radiative transfer model was used, and the model inputs were taken from the OPAC (Optical Properties of Aerosols and Clouds) utilizing only limited aerosol parameter measurements. The result shows a large overestimation of TOA warming by the latter (i.e., Model-based method).

Keywords: aerosol radiative forcing (ARF), aerosol composition, MISR, CERES, SBDART

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1129 Structural Correlates of Reduced Malicious Pleasure in Huntington's Disease

Authors: Sandra Baez, Mariana Pino, Mildred Berrio, Hernando Santamaria-Garcia, Lucas Sedeno, Adolfo Garcia, Sol Fittipaldi, Agustin Ibanez

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Schadenfreude refers to the perceiver’s experience of pleasure at another’s misfortune. This is a multidetermined emotion which can be evoked by hostile feelings and envy. The experience of Schadenfreude engages mechanisms implicated in diverse social cognitive processes. For instance, Schadenfreude involves heightened reward processing, accompanied by increased striatal engagement and it interacts with mentalizing and perspective-taking abilities. Patients with Huntington's disease (HD) exhibit reductions of Schadenfreude experience, suggesting a role of striatal degeneration in such an impairment. However, no study has directly assessed the relationship between regional brain atrophy in HD and reduced Schadenfreude. This study investigated whether gray matter (GM) atrophy in HD patients correlates with ratings of Schadenfreude. First, we compared the performance of 20 HD patients and 23 controls on an experimental task designed to trigger Schadenfreude and envy (another social emotion acting as a control condition). Second, we compared GM volume between groups. Third, we examined brain regions where atrophy might be associated with specific impairments in the patients. Results showed that while both groups showed similar ratings of envy, HD patients reported lower Schadenfreude. The latter pattern was related to atrophy in regions of the reward system (ventral striatum) and the mentalizing network (precuneus and superior parietal lobule). Our results shed light on the intertwining of reward and socioemotional processes in Schadenfreude, while offering novel evidence about their neural correlates. In addition, our results open the door to future studies investigating social emotion processing in other clinical populations characterized by striatal or mentalizing network impairments (e.g., Parkinson’s disease, schizophrenia, autism spectrum disorders).

Keywords: envy, Gray matter atrophy, Huntigton's disease, Schadenfreude, social emotions

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1128 Physical Aspects of Shape Memory and Reversibility in Shape Memory Alloys

Authors: Osman Adiguzel

Abstract:

Shape memory alloys take place in a class of smart materials by exhibiting a peculiar property called the shape memory effect. This property is characterized by the recoverability of two certain shapes of material at different temperatures. These materials are often called smart materials due to their functionality and their capacity of responding to changes in the environment. Shape memory materials are used as shape memory devices in many interdisciplinary fields such as medicine, bioengineering, metallurgy, building industry and many engineering fields. The shape memory effect is performed thermally by heating and cooling after first cooling and stressing treatments, and this behavior is called thermoelasticity. This effect is based on martensitic transformations characterized by changes in the crystal structure of the material. The shape memory effect is the result of successive thermally and stress-induced martensitic transformations. Shape memory alloys exhibit thermoelasticity and superelasticity by means of deformation in the low-temperature product phase and high-temperature parent phase region, respectively. Superelasticity is performed by stressing and releasing the material in the parent phase region. Loading and unloading paths are different in the stress-strain diagram, and the cycling loop reveals energy dissipation. The strain energy is stored after releasing, and these alloys are mainly used as deformation absorbent materials in control of civil structures subjected to seismic events, due to the absorbance of strain energy during any disaster or earthquake. Thermal-induced martensitic transformation occurs thermally on cooling, along with lattice twinning with cooperative movements of atoms by means of lattice invariant shears, and ordered parent phase structures turn into twinned martensite structures, and twinned structures turn into the detwinned structures by means of stress-induced martensitic transformation by stressing the material in the martensitic condition. Thermal induced transformation occurs with the cooperative movements of atoms in two opposite directions, <110 > -type directions on the {110} - type planes of austenite matrix which is the basal plane of martensite. Copper-based alloys exhibit this property in the metastable β-phase region, which has bcc-based structures at high-temperature parent phase field. Lattice invariant shear and twinning is not uniform in copper-based ternary alloys and gives rise to the formation of complex layered structures, depending on the stacking sequences on the close-packed planes of the ordered parent phase lattice. In the present contribution, x-ray diffraction and transmission electron microscopy (TEM) studies were carried out on two copper-based CuAlMn and CuZnAl alloys. X-ray diffraction profiles and electron diffraction patterns reveal that both alloys exhibit superlattice reflections inherited from the parent phase due to the displacive character of martensitic transformation. X-ray diffractograms taken in a long time interval show that diffraction angles and intensities of diffraction peaks change with the aging duration at room temperature. In particular, some of the successive peak pairs providing a special relation between Miller indices come close to each other. This result refers to the rearrangement of atoms in a diffusive manner.

Keywords: shape memory effect, martensitic transformation, reversibility, superelasticity, twinning, detwinning

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1127 Joubert Syndrome and Related Disorders: A Single Center Experience

Authors: Ali Al Orf, Khawaja Bilal Waheed

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Background and objective: Joubert syndrome (JS) is a rare, autosomal-recessive condition. Early recognition is important for management and counseling. Magnetic resonance imaging (MRI) can help in diagnosis. Therefore, we sought to evaluate clinical presentation and MRI findings in Joubert syndrome and related disorders. Method: A retrospective review of genetically proven cases of Joubert syndromes and related disorders was reviewed for their clinical presentation, demographic information, and magnetic resonance imaging findings in a period of the last 10 years. Two radiologists documented magnetic resonance imaging (MRI) findings. The presence of hypoplasia of the cerebellar vermis with hypoplasia of the superior cerebellar peduncle resembling the “Molar Tooth Sign” in the mid-brain was documented. Genetic testing results were collected to label genes linked to the diagnoses. Results: Out of 12 genetically proven JS cases, most were females (9/12), and nearly all presented with hypotonia, ataxia, developmental delay, intellectual impairment, and speech disorders. 5/12 children presented at age of 1 or below. The molar tooth sign was seen in 10/12 cases. Two cases were associated with other brain findings. Most of the cases were found associated with consanguineous marriage Conclusion and discussion: The molar tooth sign is a frequent and reliable sign of JS and related disorders. Genes related to defective cilia result in malfunctioning in the retina, renal tubule, and neural cell migration, thus producing heterogeneous syndrome complexes known as “ciliopathies.” Other ciliopathies like Senior-Loken syndrome, Bardet Biedl syndrome, and isolated nephronophthisis must be considered as the differential diagnosis of JS. The main imaging findings are the partial or complete absence of the cerebellar vermis, hypoplastic cerebellar peduncles (giving MTS), and (bat-wing appearance) fourth ventricular deformity. LimitationsSingle-center, small sample size, and retrospective nature of the study were a few of the study limitations.

Keywords: Joubart syndrome, magnetic resonance imaging, molar tooth sign, hypotonia

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1126 An Inquiry on Imaging of Soft Tissues in Micro-Computed Tomography

Authors: Matej Patzelt, Jana Mrzilkova, Jan Dudak, Frantisek Krejci, Jan Zemlicka, Zdenek Wurst, Petr Zach, Vladimir Musil

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Introduction: Micro-CT is well used for examination of bone structures and teeth. On the other hand visualization of the soft tissues is still limited. The goal of our study was to elaborate methodology for soft tissue samples imaging in micro-CT. Methodology: We used organs of rats and mice. We either did a preparation of the organs and fixation in contrast solution or we did cannulation of blood vessels and their injection for imaging of the vascular system. First, we scanned native specimens, then we created corrosive specimens by resins. In the next step, we injected vascular system either by Aurovist contrast agent or by Exitron. In the next step, we focused on soft tissues contrast increase. We scanned samples fixated in Lugol solution, samples fixated in pure ethanol and in formaldehyde solution. All used methods were afterwards compared. Results: Native specimens did not provide sufficient contrast of the tissues in any of organs. Corrosive samples of the blood stream provided great contrast and details; on the other hand, it was necessary to destroy the organ. Further examined possibility was injection of the AuroVist contrast that leads to the great bloodstream contrast. Injection of Exitron contrast agent comparing to Aurovist did not provide such a great contrast. The soft tissues (kidney, heart, lungs, brain, and liver) were best visualized after fixation in ethanol. This type of fixation showed best results in all studied tissues. Lugol solution had great results in muscle tissue. Fixation by formaldehyde solution showed similar quality of contrast in the tissues like ethanol. Conclusion: Before imaging, we need to, first, determinate which structures of the soft tissues we want to visualize. In the case of the bloodstream, the best was AuroVist and corrosive specimens. Muscle tissue is best visualized by Lugol solution. In the case of the organs containing cavities, like kidneys or brain, the best way was ethanol fixation.

Keywords: experimental imaging, fixation, micro-CT, soft tissues

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1125 Coronin 1C and miR-128A as Potential Diagnostic Biomarkers for Glioblastoma Multiform

Authors: Denis Mustafov, Emmanouil Karteris, Maria Braoudaki

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Glioblastoma multiform (GBM) is a heterogenous primary brain tumour that kills most affected patients. To the authors best knowledge, despite all research efforts there is no early diagnostic biomarker for GBM. MicroRNAs (miRNAs) are short non-coding RNA molecules which are deregulated in many cancers. The aim of this research was to determine miRNAs with a diagnostic impact and to potentially identify promising therapeutic targets for glioblastoma multiform. In silico analysis was performed to identify deregulated miRNAs with diagnostic relevance for glioblastoma. The expression profiles of the chosen miRNAs were then validated in vitro in the human glioblastoma cell lines A172 and U-87MG. Briefly, RNA extraction was carried out using the Trizol method, whilst miRNA extraction was performed using the mirVANA miRNA isolation kit. Quantitative Real-Time Polymerase Chain Reaction was performed to verify their expression. The presence of five target proteins within the A172 cell line was evaluated by Western blotting. The expression of the CORO1C protein within 32 GBM cases was examined via immunohistochemistry. The miRNAs identified in silico included miR-21-5p, miR-34a and miR-128a. These miRNAs were shown to target deregulated GBM genes, such as CDK6, E2F3, BMI1, JAG1, and CORO1C. miR-34a and miR-128a showed low expression profiles in comparison to a control miR-RNU-44 in both GBM cell lines suggesting tumour suppressor properties. Opposing, miR-21-5p demonstrated greater expression indicating that it could potentially function as an oncomiR. Western blotting revealed expression of all five proteins within the A172 cell line. In silico analysis also suggested that CORO1C is a target of miR-128a and miR-34a. Immunohistochemistry demonstrated that 75% of the GBM cases showed moderate to high expression of CORO1C protein. Greater understanding of the deregulated expression of miR-128a and the upregulation of CORO1C in GBM could potentially lead to the identification of a promising diagnostic biomarker signature for glioblastomas.

Keywords: non-coding RNAs, gene expression, brain tumours, immunohistochemistry

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1124 Thermal Management of a Compact Electronic Device Subjected to Different Harsh Operating Conditions

Authors: Murat Parlak, Muhammed Çağlar Malyemez

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In a harsh environment, it is crucialtoinvestigatethethermal problem systematically implement a reliableandeffectivecoolingtechniqueformilitaryequipment. In this study, an electronicaldevice has been designed to fit different boundary conditions. Manyfinalternatives can be possiblesolutionsforthethermal problem. Therefore, it is an important step to define an easyproduciblefindesignand a low power fan selection for the optimum unit-design satisfying IP68. The equipment is planned to serve at 71C environment conditions and it also can be screwedto a cold plate at +85C. In both conditions, it is intendedtousethesamechassiswithoutanymodifications. To optimize such a ruggeddevice, all CFD analysis has been done withAnsysFluent 2021®. Afterstudyingpinfins, it is seenthatthesurfacearea is not enough, hencethefin-type is changed to a straightrectangulartypewithforcedconvectioncooling. Finally, a verycompactproductthat can serve in a harsh environment is obtained.

Keywords: electronic cooling, harsh environment, forced convection, compact design

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1123 Effect of Tai-Chi and Cyclic Meditation on Hemodynamic Responses of the Prefrontal Cortex: A Functional near Infrared Spectroscopy

Authors: Singh Deepeshwar, N. K. Manjunath, M. Avinash

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Meditation is a self-regulated conscious process associated with improved awareness, perception, attention and overall performance. Different traditional origin of meditation technique may have different effects on autonomic activity and brain functions. Based on this quest, the present study evaluated the effect of Tai-Chi Chuan (TCC, a Chines movement based meditation technique) and Cyclic Meditation (CM, an Indian traditional based stimulation and relaxation meditation technique) on the hemodynamic responses of the prefrontal cortex (PFC) and autonomic functions (such as R-R interval of heart rate variability and respiration). These two meditation practices were compared with simple walking. Employing 64 channel near infrared spectroscopy (NIRS), we measured hemoglobin concentration change (i.e., Oxyhemoglobin [ΔHbO], Deoxyhemoglobin [ΔHbR] and Total hemoglobin change [ΔTHC]) in the bilateral PFC before and after TCC, CM and Walking in young college students (n=25; average mean age ± SD; 23.4 ± 3.1 years). We observed the left PFC activity predominantly modulates sympathetic activity effects during the Tai-Chi whereas CM showed changes on right PFC with vagal dominance. However, the changes in oxyhemoglobin and total blood volume change after Tai-Chi was significant higher (p < 0.05, spam t-maps) on the left hemisphere, whereas after CM, there was a significant increase in oxyhemoglobin (p < 0.01) with a decrease in deoxyhemoglobin (p < 0.05) on right PFC. The normal walking showed decrease in Oxyhemoglobin with an increase in deoxyhemoglobin on left PFC. The autonomic functions result showed a significant increase in RR- interval (p < 0.05) along with significant reductions in HR (p < 0.05) in CM, whereas Tai-chi session showed significant increase in HR (p < 0.05) when compared to walking session. Within a group analysis showed a significant reduction in RR-I and significant increase in HR both in Tai-chi and walking sessions. The CM showed there were a significant improvement in the RR - interval of HRV (p < 0.01) with the reduction of heart rate and breath rate (p < 0.05). The result suggested that Tai-Chi and CM both have a positive effect on left and right prefrontal cortex and increase sympathovagal balance (alertful rest) in autonomic nervous system activity.

Keywords: brain, hemodynamic responses, yoga, meditation, Tai-Chi Chuan (TCC), walking, heart rate variability (HRV)

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1122 Ultrasonic Micro Injection Molding: Manufacturing of Micro Plates of Biomaterials

Authors: Ariadna Manresa, Ines Ferrer

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Introduction: Ultrasonic moulding process (USM) is a recent injection technology used to manufacture micro components. It is able to melt small amounts of material so the waste of material is certainly reduced comparing to microinjection molding. This is an important advantage when the materials are expensive like medical biopolymers. Micro-scaled components are involved in a variety of uses, such as biomedical applications. It is required replication fidelity so it is important to stabilize the process and minimize the variability of the responses. The aim of this research is to investigate the influence of the main process parameters on the filling behaviour, the dimensional accuracy and the cavity pressure when a micro-plate is manufactured by biomaterials such as PLA and PCL. Methodology or Experimental Procedure: The specimens are manufactured using a Sonorus 1G Ultrasound Micro Molding Machine. The used geometry is a rectangular micro-plate of 15x5mm and 1mm of thickness. The materials used for the investigation are PLA and PCL due to biocompatible and degradation properties. The experimentation is divided into two phases. Firstly, the influence of process parameters (vibration amplitude, sonotrodo velocity, ultrasound time and compaction force) on filling behavior is analysed, in Phase 1. Next, when filling cavity is assured, the influence of both cooling time and force compaction on the cavity pressure, part temperature and dimensional accuracy is instigated, which is done in Phase. Results and Discussion: Filling behavior depends on sonotrodo velocity and vibration amplitude. When the ultrasonic time is higher, more ultrasonic energy is applied and the polymer temperature increases. Depending on the cooling time, it is possible that when mold is opened, the micro-plate temperature is too warm. Consequently, the polymer relieve its stored internal energy (ultrasonic and thermal) expanding through the easier direction. This fact is reflected on dimensional accuracy, causing micro-plates thicker than the mold. It has also been observed the most important fact that affects cavity pressure is the compaction configuration during the manufacturing cycle. Conclusions: This research demonstrated the influence of process parameters on the final micro-plated manufactured. Future works will be focused in manufacturing other geometries and analysing the mechanical properties of the specimens.

Keywords: biomaterial, biopolymer, micro injection molding, ultrasound

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1121 Effect of Cutting Tools and Working Conditions on the Machinability of Ti-6Al-4V Using Vegetable Oil-Based Cutting Fluids

Authors: S. Gariani, I. Shyha

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Cutting titanium alloys are usually accompanied with low productivity, poor surface quality, short tool life and high machining costs. This is due to the excessive generation of heat at the cutting zone and difficulties in heat dissipation due to relatively low heat conductivity of this metal. The cooling applications in machining processes are crucial as many operations cannot be performed efficiently without cooling. Improving machinability, increasing productivity, enhancing surface integrity and part accuracy are the main advantages of cutting fluids. Conventional fluids such as mineral oil-based, synthetic and semi-synthetic are the most common cutting fluids in the machining industry. Although, these cutting fluids are beneficial in the industries, they pose a great threat to human health and ecosystem. Vegetable oils (VOs) are being investigated as a potential source of environmentally favourable lubricants, due to a combination of biodegradability, good lubricous properties, low toxicity, high flash points, low volatility, high viscosity indices and thermal stability. Fatty acids of vegetable oils are known to provide thick, strong, and durable lubricant films. These strong lubricating films give the vegetable oil base stock a greater capability to absorb pressure and high load carrying capacity. This paper details preliminary experimental results when turning Ti-6Al-4V. The impact of various VO-based cutting fluids, cutting tool materials, working conditions was investigated. The full factorial experimental design was employed involving 24 tests to evaluate the influence of process variables on average surface roughness (Ra), tool wear and chip formation. In general, Ra varied between 0.5 and 1.56 µm and Vasco1000 cutting fluid presented comparable performance with other fluids in terms of surface roughness while uncoated coarse grain WC carbide tool achieved lower flank wear at all cutting speeds. On the other hand, all tools tips were subjected to uniform flank wear during whole cutting trails. Additionally, formed chip thickness ranged between 0.1 and 0.14 mm with a noticeable decrease in chip size when higher cutting speed was used.

Keywords: cutting fluids, turning, Ti-6Al-4V, vegetable oils, working conditions

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1120 Experimental Study on Temperature Splitting of a Counter-Flow Ranque-Hilsch Vortex Tube

Authors: Hany. A. Mohamed, M. Attalla, M. Salem, Hussein M. Mghrabie, E. Specht

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An experiment al investigation is made to determine the effects of the nozzle dimensions and the inlet pressure on the heating and cooling performance of the counter flow Ranque–Hilsch vortex tube when air used as a working fluid. The all results were taking under inlet pressures were adjusted from 200 kPa to 600 kPa with 100 kPa increments. The conventional tangential generator with number of nuzzle of 6 was used and inner diameter of 7.5 mm. During the experiments, a vortex tube is used with an L/D ratio varied from 10 to 30. Finally, it is observed that the effect of the nuzzle aspect ratio on the energy separation changes according to the value of L/D.

Keywords: Ranque-Hilsch, vortex tube, aspect ratio, energy separation

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1119 Altered States of Consciousness in Narrative Cinema: Subjective Film Sound

Authors: Mladen Milicevic

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In this paper, subjective film sound will be addressed as it gets represented in narrative cinema. First, 'meta-diegetic' sound will be briefly explained followed by transition to “oneiric” sound. The representation of oneiric sound refers to a situation where film characters are experiencing some sort of an altered state of consciousness. Looking at an antlered state of consciousness in terms of human brain processes will point out to the cinematic ways of expression, which 'mimic' those processes. Using several examples for different films will illustrate these points.

Keywords: oneiric, ASC, film, sound

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1118 The Closed Cavity Façade (CCF): Optimization of CCF for Enhancing Energy Efficiency and Indoor Environmental Quality in Office Buildings

Authors: Michalis Michael, Mauro Overend

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Buildings, in which we spend 87-90% of our time, act as a shelter protecting us from environmental conditions and weather phenomena. The building's overall performance is significantly dependent on the envelope’s glazing part, which is particularly critical as it is the most vulnerable part to heat gain and heat loss. However, conventional glazing technologies have relatively low-performance thermo-optical characteristics. In this regard, during winter, the heat losses due to the glazing part of a building envelope are significantly increased as well as the heat gains during the summer period. In this study, the contribution of an innovative glazing technology, namely Closed Cavity Façade (CCF) in improving energy efficiency and IEQ in office buildings is examined, aiming to optimize various design configurations of CCF. Using Energy Plus and IDA ICE packages, the performance of several CCF configurations and geometries for various climate types were investigated, aiming to identify the optimum solution. The model used for the simulations and optimization process was MATELab, a recently constructed outdoor test facility at the University of Cambridge (UK). The model was previously experimentally calibrated. The study revealed that the use of CCF technology instead of conventional double or triple glazing leads to important benefits. Particularly, the replacement of the traditional glazing units, used as the baseline, with the optimal configuration of CCF led to a decrease in energy consumption in the range of 18-37% (depending on the location). This mainly occurs due to integrating shading devices in the cavity and applying proper glass coatings and control strategies, which lead to improvement of thermal transmittance and g-value of the glazing. Since the solar gain through the façade is the main contributor to energy consumption during cooling periods, it was observed that a higher energy improvement is achieved in cooling-dominated locations. Furthermore, it was shown that a suitable selection of the constituents of a closed cavity façade, such as the colour and type of shading devices and the type of coatings, leads to an additional improvement of its thermal performance, avoiding overheating phenomena and consequently ensuring temperatures in the glass cavity below the critical value, and reducing the radiant discomfort providing extra benefits in terms of Indoor Environmental Quality (IEQ).

Keywords: building energy efficiency, closed cavity façade, optimization, occupants comfort

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1117 Effect of Fire on Structural Behavior of Normal and High Strength Concrete Beams

Authors: Alaa I. Arafa, Hemdan O. A. Said. Marwa A. M. Ali

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This paper investigates and evaluates experimentally the structural behavior of high strength concrete (HSC) beams under fire and compares it with that of Normal strength concrete (NSC) beams. The main investigated parameters are: concrete compressive strength (300 or 600 kg/cm2); the concrete cover thickness (3 or 5 cm); the degree of temperature (room temperature or 600 oC); the type of cooling (air or water); and the fire exposure time (3 or 5 hours). Test results showed that the concrete compressive strength decreases significantly as the exposure time to fire increases.

Keywords: experimental, fire, high strength concrete beams, monotonic loading

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1116 Heat Transfer Enhancement via Using Al2O3/Water Nanofluid in Car Radiator

Authors: S. Movafagh, Y. Bakhshan

Abstract:

In this study, effect of adding Al2O3 nanoparticle to base fluid (water) in car radiator is investigated numerically. Radiators are compact heat exchangers optimized and evaluated by considering different working conditions. The cooling system of a car plays an important role in vehicle's performance, consists of two main parts, known as radiator and fan. Improving thermal efficiency of engine leads to increase the engine's performance, decline the fuel consumption and decrease the pollution emissions. In this study, the effects of fluid inlet flow rate and nanoparticle volume fraction on heat transfer and pressure drop of acar radiator are studied.

Keywords: forced convection, nanofluid, radiator, CFD simulation

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1115 Effect of Springback Analysis on Influences of the Steel Demoulding Using FEM

Authors: Byeong-Sam Kim, Jongmin Park

Abstract:

The present work is motivated by the industrial challenge to produce complex composite shapes cost-effectively. The model used an anisotropical thermoviscoelastic is analyzed by an implemented finite element solver. The stress relaxation can be constructed by Prony series for the nonlinear thermoviscoelastic model. The calculation of process induced internal stresses relaxation during the cooling stage of the manufacturing cycle was carried out by the spring back phenomena observed from the part containing a cylindrical segment. The finite element results obtained from the present formulation are compared with experimental data, and the results show good correlations.

Keywords: thermoviscoelastic, springback phenomena, FEM analysis, thermoplastic composite structures

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1114 Reduction of Residual Stress by Variothermal Processing and Validation via Birefringence Measurement Technique on Injection Molded Polycarbonate Samples

Authors: Christoph Lohr, Hanna Wund, Peter Elsner, Kay André Weidenmann

Abstract:

Injection molding is one of the most commonly used techniques in the industrial polymer processing. In the conventional process of injection molding, the liquid polymer is injected into the cavity of the mold, where the polymer directly starts hardening at the cooled walls. To compensate the shrinkage, which is caused predominantly by the immediate cooling, holding pressure is applied. Through that whole process, residual stresses are produced by the temperature difference of the polymer melt and the injection mold and the relocation of the polymer chains, which were oriented by the high process pressures and injection speeds. These residual stresses often weaken or change the structural behavior of the parts or lead to deformation of components. One solution to reduce the residual stresses is the use of variothermal processing. Hereby the mold is heated – i.e. near/over the glass transition temperature of the polymer – the polymer is injected and before opening the mold and ejecting the part the mold is cooled. For the next cycle, the mold gets heated again and the procedure repeats. The rapid heating and cooling of the mold are realized indirectly by convection of heated and cooled liquid (here: water) which is pumped through fluid channels underneath the mold surface. In this paper, the influences of variothermal processing on the residual stresses are analyzed with samples in a larger scale (500 mm x 250 mm x 4 mm). In addition, the influence on functional elements, such as abrupt changes in wall thickness, bosses, and ribs, on the residual stress is examined. Therefore the polycarbonate samples are produced by variothermal and isothermal processing. The melt is injected into a heated mold, which has in our case a temperature varying between 70 °C and 160 °C. After the filling of the cavity, the closed mold is cooled down varying from 70 °C to 100 °C. The pressure and temperature inside the mold are monitored and evaluated with cavity sensors. The residual stresses of the produced samples are illustrated by birefringence where the effect on the refractive index on the polymer under stress is used. The colorful spectrum can be uncovered by placing the sample between a polarized light source and a second polarization filter. To show the achievement and processing effects on the reduction of residual stress the birefringence images of the isothermal and variothermal produced samples are compared and evaluated. In this comparison to the variothermal produced samples have a lower amount of maxima of each color spectrum than the isothermal produced samples, which concludes that the residual stress of the variothermal produced samples is lower.

Keywords: birefringence, injection molding, polycarbonate, residual stress, variothermal processing

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1113 CFD Modeling of Stripper Ash Cooler of Circulating Fluidized Bed

Authors: Ravi Inder Singh

Abstract:

Due to high heat transfer rate, high carbon utilizing efficiency, fuel flexibilities and other advantages numerous circulating fluidized bed boilers have grown up in India in last decade. Many companies like BHEL, ISGEC, Thermax, Cethar Limited, Enmas GB Power Systems Projects Limited are making CFBC and installing the units throughout the India. Due to complexity many problems exists in CFBC units and only few have been reported. Agglomeration i.e clinker formation in riser, loop seal leg and stripper ash coolers is one of problem industry is facing. Proper documentation is rarely found in the literature. Circulating fluidized bed (CFB) boiler bottom ash contains large amounts of physical heat. While the boiler combusts the low-calorie fuel, the ash content is normally more than 40% and the physical heat loss is approximately 3% if the bottom ash is discharged without cooling. In addition, the red-hot bottom ash is bad for mechanized handling and transportation, as the upper limit temperature of the ash handling machinery is 200 °C. Therefore, a bottom ash cooler (BAC) is often used to treat the high temperature bottom ash to reclaim heat, and to have the ash easily handled and transported. As a key auxiliary device of CFB boilers, the BAC has a direct influence on the secure and economic operation of the boiler. There are many kinds of BACs equipped for large-scale CFB boilers with the continuous development and improvement of the CFB boiler. These ash coolers are water cooled ash cooling screw, rolling-cylinder ash cooler (RAC), fluidized bed ash cooler (FBAC).In this study prototype of a novel stripper ash cooler is studied. The Circulating Fluidized bed Ash Coolers (CFBAC) combined the major technical features of spouted bed and bubbling bed, and could achieve the selective discharge on the bottom ash. The novel stripper ash cooler is bubbling bed and it is visible cold test rig. The reason for choosing cold test is that high temperature is difficult to maintain and create in laboratory level. The aim of study to know the flow pattern inside the stripper ash cooler. The cold rig prototype is similar to stripper ash cooler used industry and it was made after scaling down to some parameter. The performance of a fluidized bed ash cooler is studied using a cold experiment bench. The air flow rate, particle size of the solids and air distributor type are considered to be the key parameters of the operation of a fluidized bed ash cooler (FBAC) are studied in this.

Keywords: CFD, Eulerian-Eulerian, Eulerian-Lagraingian model, parallel simulations

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1112 Electric Power Generation by Thermoelectric Cells and Parabolic Solar Concentrators

Authors: A. Kianifar, M. Afzali, I. Pishbin

Abstract:

In this paper, design details, theoretical analysis and thermal performance analysis of a solar energy concentrator suited to combined heat and thermoelectric power generation are presented. The thermoelectric device is attached to the absorber plate to convert concentrated solar energy directly into electric energy at the focus of the concentrator. A cooling channel (water cooled heat sink) is fitted to the cold side of the thermoelectric device to remove the waste heat and maintain a high temperature gradient across the device to improve conversion efficiency.

Keywords: concentrator thermoelectric generator, CTEG, solar energy, thermoelectric cells

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1111 Effect of Papaverine on Developmental Neurotoxicity: Neurosphere as in vitro Model

Authors: Mohammed Y. Elsherbeny, Mohamed Salama, Ahmed Lotfy, Hossam Fareed, Nora Mohammed

Abstract:

Background: Developmental neurotoxicity (DNT) entails the toxic effects imparted by various chemicals on brain during the early childhood when human brains are vulnerable during this period. DNT study in vivo cannot determine the effect of the neurotoxins, as it is not applicable, so using the neurosphere cells of lab animals as an alternative is applicable and time saving. Methods: Cell culture: Rat neural progenitor cells were isolated from rat embryos’ brain. The cortices were aseptically dissected out and the tissues were triturated. The dispersed tissues were allowed to settle. The supernatant was then transferred to a fresh tube and centrifuged. The pellet was placed in Hank’s balanced salt solution and cultured as free-floating neurospheres in proliferation medium. Differentiation was initiated by growth factor withdrawal in differentiation medium and plating onto a poly-d-lysine/ laminin matrix. Chemical Exposure: Neurospheres were treated for 2 weeks with papaverine in proliferation medium. Proliferation analyses: Spheres were cultured. After 0, 4, 5, 11 and 14 days, sphere size was determined by software analyses (CellProfiler, version 2.1; Broad Institute). Diameter of each neurosphere was measured and exported to excel file further to statistical analysis. Viability test: Trypsin-EDTA solution was added to neurospheres to dissociate neurospheres into single cells suspension, then viability evaluated by the Trypan Blue exclusion test. Result: As regards proliferation analysis and percentage of viable cells of papaverin treated groups: There was no significant change in cells proliferation compared to control at 0, 4, 5, 11 and 14 days with concentrations 1, 5 and 10 µM of papaverine, but there is a significant change in cell viability compared to control after 1 week and 2 weeks with the same concentrations of papaverine. Conclusion: Papaverine has toxic effect on viability of neural cell, not on their proliferation, so it may produce focal neural lesions not growth morphological changes.

Keywords: developmental neurotoxicity, neurotoxin, papaverine, neuroshperes

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1110 A Comparative Case Study of the Impact of Square and Yurt-Shape Buildings on Energy Efficiency

Authors: Valeriya Tyo, Serikbolat Yessengabulov

Abstract:

Regions with extreme climate conditions such as Astana city require energy saving measures to increase the energy performance of buildings which are responsible for more than 40% of total energy consumption. Identification of optimal building geometry is one of the key factors to be considered. The architectural form of a building has the impact on space heating and cooling energy use, however, the interrelationship between the geometry and resultant energy use is not always readily apparent. This paper presents a comparative case study of two prototypical buildings with compact building shape to assess its impact on energy performance.

Keywords: building geometry, energy efficiency, heat gain, heat loss

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1109 Condensation of Vapor in the Presence of Non-Condensable Gas on a Vertical Tube

Authors: Shengjun Zhang, Xu Cheng, Feng Shen

Abstract:

The passive containment cooling system (PCCS) is widely used in the advanced nuclear reactor in case of the loss of coolant accident (LOCA) and the main steam line break accident (MSLB). The internal heat exchanger is one of the most important equipment in the PCCS and its heat transfer characteristic determines the performance of the system. In this investigation, a theoretical model is presented for predicting the heat and mass transfer which accompanies condensation. The conduction through the liquid condensate is considered and the interface temperature is defined by iteration. The parameter in the correlation to describe the suction effect should be further determined through experimental data.

Keywords: non-condensable gas, condensation, heat transfer coefficient, heat and mass transfer analogy

Procedia PDF Downloads 346
1108 Connectomic Correlates of Cerebral Microhemorrhages in Mild Traumatic Brain Injury Victims with Neural and Cognitive Deficits

Authors: Kenneth A. Rostowsky, Alexander S. Maher, Nahian F. Chowdhury, Andrei Irimia

Abstract:

The clinical significance of cerebral microbleeds (CMBs) due to mild traumatic brain injury (mTBI) remains unclear. Here we use magnetic resonance imaging (MRI), diffusion tensor imaging (DTI) and connectomic analysis to investigate the statistical association between mTBI-related CMBs, post-TBI changes to the human connectome and neurological/cognitive deficits. This study was undertaken in agreement with US federal law (45 CFR 46) and was approved by the Institutional Review Board (IRB) of the University of Southern California (USC). Two groups, one consisting of 26 (13 females) mTBI victims and another comprising 26 (13 females) healthy control (HC) volunteers were recruited through IRB-approved procedures. The acute Glasgow Coma Scale (GCS) score was available for each mTBI victim (mean µ = 13.2; standard deviation σ = 0.4). Each HC volunteer was assigned a GCS of 15 to indicate the absence of head trauma at the time of enrollment in our study. Volunteers in the HC and mTBI groups were matched according to their sex and age (HC: µ = 67.2 years, σ = 5.62 years; mTBI: µ = 66.8 years, σ = 5.93 years). MRI [including T1- and T2-weighted volumes, gradient recalled echo (GRE)/susceptibility weighted imaging (SWI)] and gradient echo (GE) DWI volumes were acquired using the same MRI scanner type (Trio TIM, Siemens Corp.). Skull-stripping and eddy current correction were implemented. DWI volumes were processed in TrackVis (http://trackvis.org) and 3D Slicer (http://www.slicer.org). Tensors were fit to DWI data to perform DTI, and tractography streamlines were then reconstructed using deterministic tractography. A voxel classifier was used to identify image features as CMB candidates using Microbleed Anatomic Rating Scale (MARS) guidelines. For each peri-lesional DTI streamline bundle, the null hypothesis was formulated as the statement that there was no neurological or cognitive deficit associated with between-scan differences in the mean FA of DTI streamlines within each bundle. The statistical significance of each hypothesis test was calculated at the α = 0.05 level, subject to the family-wise error rate (FWER) correction for multiple comparisons. Results: In HC volunteers, the along-track analysis failed to identify statistically significant differences in the mean FA of DTI streamline bundles. In the mTBI group, significant differences in the mean FA of peri-lesional streamline bundles were found in 21 out of 26 volunteers. In those volunteers where significant differences had been found, these differences were associated with an average of ~47% of all identified CMBs (σ = 21%). In 12 out of the 21 volunteers exhibiting significant FA changes, cognitive functions (memory acquisition and retrieval, top-down control of attention, planning, judgment, cognitive aspects of decision-making) were found to have deteriorated over the six months following injury (r = -0.32, p < 0.001). Our preliminary results suggest that acute post-TBI CMBs may be associated with cognitive decline in some mTBI patients. Future research should attempt to identify mTBI patients at high risk for cognitive sequelae.

Keywords: traumatic brain injury, magnetic resonance imaging, diffusion tensor imaging, connectomics

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1107 The Impact of Roof Thermal Performance on the Indoor Thermal Comfort in a Natural Ventilated Building Envelope in Hot Climatic Climates

Authors: J. Iwaro, A. Mwasha, K. Ramsubhag

Abstract:

Global warming has become a threat of our time. It poses challenges to the existence of beings on earth, the built environment, natural environment and has made a clear impact on the level of energy and water consumption. As such, increase in the ambient temperature increases indoor and outdoor temperature level of the buildings which brings about the use of more energy and mechanical air conditioning systems. In addition, in view of the increased modernization and economic growth in the developing countries, a significant amount of energy is being used, especially those with hot climatic conditions. Since modernization in developing countries is rising rapidly, more pressure is being placed on the buildings and energy resources to satisfy the indoor comfort requirements. This paper presents a sustainable passive roof solution as a means of reducing energy cooling loads for satisfying human comfort requirements in a hot climate. As such, the study based on the field study data discusses indoor thermal roof design strategies for a hot climate by investigating the impacts of roof thermal performance on indoor thermal comfort in naturally ventilated building envelope small scaled structures. In this respect, the traditional concrete flat roof, corrugated galvanised iron roof and pre-painted standing seam roof were used. The experiment made used of three identical small scale physical models constructed and sited on the roof of a building at the University of the West Indies. The results show that the utilization of insulation in traditional roofing systems will significantly reduce heat transfer between the internal and ambient environment, thus reducing the energy demand of the structure and the relative carbon footprint of a structure per unit area over its lifetime. Also, the application of flat slab concrete roofing system showed the best performance as opposed to the metal roof sheeting alternative systems. In addition, it has been shown experimentally through this study that a sustainable passive roof solution such as insulated flat concrete roof in hot dry climate has a better cooling strength that can provide building occupant with a better thermal comfort, conducive indoor conditions and energy efficiency.

Keywords: building envelope, roof, energy consumption, thermal comfort

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1106 CD97 and Its Role in Glioblastoma Stem Cell Self-Renewal

Authors: Niklas Ravn-Boess, Nainita Bhowmick, Takamitsu Hattori, Shohei Koide, Christopher Park, Dimitris Placantonakis

Abstract:

Background: Glioblastoma (GBM) is the most common and deadly primary brain malignancy in adults. Tumor propagation, brain invasion, and resistance to therapy critically depend on GBM stem-like cells (GSCs); however, the mechanisms that regulate GSC self-renewal are incompletely understood. Given the aggressiveness and poor prognosis of GBM, it is imperative to find biomarkers that could also translate into novel drug targets. Along these lines, we have identified a cell surface antigen, CD97 (ADGRE5), an adhesion G protein-coupled receptor (GPCR), that is expressed on GBM cells but is absent from non-neoplastic brain tissue. CD97 has been shown to promote invasiveness, angiogenesis, and migration in several human cancers, but its frequency of expression and functional role in regulating GBM growth and survival, and its potential as a therapeutic target has not been investigated. Design: We assessed CD97 mRNA and protein expression in patient derived GBM samples and cell lines using publicly available RNA-sequencing datasets and flow cytometry, respectively. To assess CD97 function, we generated shRNA lentiviral constructs that target a sequence in the CD97 extracellular domain (ECD). A scrambled shRNA (scr) with no predicted targets in the genome was used as a control. We evaluated CD97 shRNA lentivirally transduced GBM cells for Ki67, Annexin V, and DAPI. We also tested CD97 KD cells for their ability to self-renew using clonogenic tumorsphere formation assays. Further, we utilized synthetic Abs (sAbs) generated against the ECD of CD97 to test for potential antitumor effects using patient-derived GBM cell lines. Results: CD97 mRNA expression was expressed at high levels in all GBM samples available in the TCGA cohort. We found high levels of surface CD97 protein expression in 6/6 patient-derived GBM cell cultures, but not human neural stem cells. Flow cytometry confirmed downregulation of CD97 in CD97 shRNA lentivirally transduced cells. CD97 KD induced a significant reduction in cell growth in 3 independent GBM cell lines representing mesenchymal and proneural subtypes, which was accompanied by reduced (~20%) Ki67 staining and increased (~30%) apoptosis. Incubation of GBM cells with sAbs (20 ug/ ml) against the ECD of CD97 for 3 days induced GSC differentiation, as determined by the expression of GFAP and Tubulin. Using three unique GBM patient derived cultures, we found that CD97 KD attenuated the ability of GBM cells to initiate sphere formation by over 300 fold, consistent with an impairment in GSC self-renewal. Conclusion: Loss of CD97 expression in patient-derived GBM cells markedly decreases proliferation, induces cell death, and reduces tumorsphere formation. sAbs against the ECD of CD97 reduce tumorsphere formation, recapitulating the phenotype of CD97 KD, suggesting that sAbs that inhibit CD97 function exhibit anti-tumor activity. Collectively, these findings indicate that CD97 is necessary for the proliferation and survival of human GBM cells and identify CD97 as a promising therapeutically targetable vulnerability in GBM.

Keywords: adhesion GPCR, CD97, GBM stem cell, glioblastoma

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1105 Defective Autophagy Disturbs Neural Migration and Network Activity in hiPSC-Derived Cockayne Syndrome B Disease Models

Authors: Julia Kapr, Andrea Rossi, Haribaskar Ramachandran, Marius Pollet, Ilka Egger, Selina Dangeleit, Katharina Koch, Jean Krutmann, Ellen Fritsche

Abstract:

It is widely acknowledged that animal models do not always represent human disease. Especially human brain development is difficult to model in animals due to a variety of structural and functional species-specificities. This causes significant discrepancies between predicted and apparent drug efficacies in clinical trials and their subsequent failure. Emerging alternatives based on 3D in vitro approaches, such as human brain spheres or organoids, may in the future reduce and ultimately replace animal models. Here, we present a human induced pluripotent stem cell (hiPSC)-based 3D neural in a vitro disease model for the Cockayne Syndrome B (CSB). CSB is a rare hereditary disease and is accompanied by severe neurologic defects, such as microcephaly, ataxia and intellectual disability, with currently no treatment options. Therefore, the aim of this study is to investigate the molecular and cellular defects found in neural hiPSC-derived CSB models. Understanding the underlying pathology of CSB enables the development of treatment options. The two CSB models used in this study comprise a patient-derived hiPSC line and its isogenic control as well as a CSB-deficient cell line based on a healthy hiPSC line (IMR90-4) background thereby excluding genetic background-related effects. Neurally induced and differentiated brain sphere cultures were characterized via RNA Sequencing, western blot (WB), immunocytochemistry (ICC) and multielectrode arrays (MEAs). CSB-deficiency leads to an altered gene expression of markers for autophagy, focal adhesion and neural network formation. Cell migration was significantly reduced and electrical activity was significantly increased in the disease cell lines. These data hint that the cellular pathologies is possibly underlying CSB. By induction of autophagy, the migration phenotype could be partially rescued, suggesting a crucial role of disturbed autophagy in defective neural migration of the disease lines. Altered autophagy may also lead to inefficient mitophagy. Accordingly, disease cell lines were shown to have a lower mitochondrial base activity and a higher susceptibility to mitochondrial stress induced by rotenone. Since mitochondria play an important role in neurotransmitter cycling, we suggest that defective mitochondria may lead to altered electrical activity in the disease cell lines. Failure to clear the defective mitochondria by mitophagy and thus missing initiation cues for new mitochondrial production could potentiate this problem. With our data, we aim at establishing a disease adverse outcome pathway (AOP), thereby adding to the in-depth understanding of this multi-faced disorder and subsequently contributing to alternative drug development.

Keywords: autophagy, disease modeling, in vitro, pluripotent stem cells

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