Search results for: motor cortex stimulation
Commenced in January 2007
Frequency: Monthly
Edition: International
Paper Count: 1400

Search results for: motor cortex stimulation

290 Time Effective Structural Frequency Response Testing with Oblique Impact

Authors: Khoo Shin Yee, Lian Yee Cheng, Ong Zhi Chao, Zubaidah Ismail, Siamak Noroozi

Abstract:

Structural frequency response testing is accurate in identifying the dynamic characteristic of a machinery structure. In practical perspective, conventional structural frequency response testing such as experimental modal analysis with impulse technique (also known as “impulse testing”) has limitation especially on its long acquisition time. The high acquisition time is mainly due to the redundancy procedure where the engineer has to repeatedly perform the test in 3 directions, namely the axial-, horizontal- and vertical-axis, in order to comprehensively define the dynamic behavior of a 3D structure. This is unfavorable to numerous industries where the downtime cost is high. This study proposes to reduce the testing time by using oblique impact. Theoretically, a single oblique impact can induce significant vibration responses and vibration modes in all the 3 directions. Hence, the acquisition time with the implementation of the oblique impulse technique can be reduced by a factor of three (i.e. for a 3D dynamic system). This study initiates an experimental investigation of impulse testing with oblique excitation. A motor-driven test rig has been used for the testing purpose. Its dynamic characteristic has been identified using the impulse testing with the conventional normal impact and the proposed oblique impact respectively. The results show that the proposed oblique impulse testing is able to obtain all the desired natural frequencies in all 3 directions and thus providing a feasible solution for a fast and time effective way of conducting the impulse testing.

Keywords: frequency response function, impact testing, modal analysis, oblique angle, oblique impact

Procedia PDF Downloads 484
289 Decomposition of the Discount Function Into Impatience and Uncertainty Aversion. How Neurofinance Can Help to Understand Behavioral Anomalies

Authors: Roberta Martino, Viviana Ventre

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Intertemporal choices are choices under conditions of uncertainty in which the consequences are distributed over time. The Discounted Utility Model is the essential reference for describing the individual in the context of intertemporal choice. The model is based on the idea that the individual selects the alternative with the highest utility, which is calculated by multiplying the cardinal utility of the outcome, as if the reception were instantaneous, by the discount function that determines a decrease in the utility value according to how the actual reception of the outcome is far away from the moment the choice is made. Initially, the discount function was assumed to have an exponential trend, whose decrease over time is constant, in line with a profile of a rational investor described by classical economics. Instead, empirical evidence called for the formulation of alternative, hyperbolic models that better represented the actual actions of the investor. Attitudes that do not comply with the principles of classical rationality are termed anomalous, i.e., difficult to rationalize and describe through normative models. The development of behavioral finance, which describes investor behavior through cognitive psychology, has shown that deviations from rationality are due to the limited rationality condition of human beings. What this means is that when a choice is made in a very difficult and information-rich environment, the brain does a compromise job between the cognitive effort required and the selection of an alternative. Moreover, the evaluation and selection phase of the alternative, the collection and processing of information, are dynamics conditioned by systematic distortions of the decision-making process that are the behavioral biases involving the individual's emotional and cognitive system. In this paper we present an original decomposition of the discount function to investigate the psychological principles of hyperbolic discounting. It is possible to decompose the curve into two components: the first component is responsible for the smaller decrease in the outcome as time increases and is related to the individual's impatience; the second component relates to the change in the direction of the tangent vector to the curve and indicates how much the individual perceives the indeterminacy of the future indicating his or her aversion to uncertainty. This decomposition allows interesting conclusions to be drawn with respect to the concept of impatience and the emotional drives involved in decision-making. The contribution that neuroscience can make to decision theory and inter-temporal choice theory is vast as it would allow the description of the decision-making process as the relationship between the individual's emotional and cognitive factors. Neurofinance is a discipline that uses a multidisciplinary approach to investigate how the brain influences decision-making. Indeed, considering that the decision-making process is linked to the activity of the prefrontal cortex and amygdala, neurofinance can help determine the extent to which abnormal attitudes respect the principles of rationality.

Keywords: impatience, intertemporal choice, neurofinance, rationality, uncertainty

Procedia PDF Downloads 110
288 Smartphone Addiction and Reaction Time in Geriatric Population

Authors: Anjali N. Shete, G. D. Mahajan, Nanda Somwanshi

Abstract:

Context: Smartphones are the new generation of mobile phones; they have emerged over the last few years. Technology has developed so much that it has become part of our life and mobile phones are one of them. These smartphones are equipped with the capabilities to display photos, play games, watch videos and navigation, etc. The advances have a huge impact on many walks of life. The adoption of new technology has been challenging for the elderly. But, the elder population is also moving towards digitally connected lives. As age advances, there is a decline in the motor and cognitive functions of the brain, and hence the reaction time is affected. The study was undertaken to assess the usefulness of smartphones in improving cognitive functions. Aims and Objectives: The aim of the study was to observe the effects of smartphone addiction on reaction time in elderly population Material and Methods: This is an experimental study. 100 elderly subjects were enrolled in this study randomly from urban areas. They all were using smartphones for several hours a day. They were divided into two groups according to the scores of the mobile phone addiction scale (MPAS). Simple reaction time was estimated by the Ruler drop method. The reaction time was then calculated for each subject in both groups. The data were analyzed using mean, standard deviation, and Pearson correlation test. Results: The mean reaction time in Group A is 0.27+ 0.040 and in Group B is 0.20 + 0.032. The values show a statistically significant change in reaction time. Conclusion: Group A with a high MPAS score has a low reaction time compared to Group B with a low MPAS score. Hence, it can be concluded that the use of smartphones in the elderly is useful, delaying the neurological decline, and smarten the brain.

Keywords: smartphones, MPAS, reaction time, elderly population

Procedia PDF Downloads 157
287 Fault Analysis of Induction Machine Using Finite Element Method (FEM)

Authors: Wiem Zaabi, Yemna Bensalem, Hafedh Trabelsi

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The paper presents a finite element (FE) based efficient analysis procedure for induction machine (IM). The FE formulation approaches are proposed to achieve this goal: the magnetostatic and the non-linear transient time stepped formulations. The study based on finite element models offers much more information on the phenomena characterizing the operation of electrical machines than the classical analytical models. This explains the increase of the interest for the finite element investigations in electrical machines. Based on finite element models, this paper studies the influence of the stator and the rotor faults on the behavior of the IM. In this work, a simple dynamic model for an IM with inter-turn winding fault and a broken bar fault is presented. This fault model is used to study the IM under various fault conditions and severity. The simulation results are conducted to validate the fault model for different levels of fault severity. The comparison of the results obtained by simulation tests allowed verifying the precision of the proposed FEM model. This paper presents a technical method based on Fast Fourier Transform (FFT) analysis of stator current and electromagnetic torque to detect the faults of broken rotor bar. The technique used and the obtained results show clearly the possibility of extracting signatures to detect and locate faults.

Keywords: Finite element Method (FEM), Induction motor (IM), short-circuit fault, broken rotor bar, Fast Fourier Transform (FFT) analysis

Procedia PDF Downloads 281
286 Guillain Barre Syndrome in Children

Authors: A. Erragh, K. Amanzoui, M. Elharit, H. Salem, M. Ababneh, K. Elfakhr, S. Kalouch, A. Chlilek

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Guillain-Barre syndrome (GBS) is the most common form of acute polyradiculoneuritis (PRNA). It is a medical emergency in pediatrics that requires rapid diagnosis and immediate assessment of the severity criteria for the implementation of appropriate treatment. Retrospective, descriptive study in 24 patients under the age of 18 who presented with GBS between September 2017 and July 2021 and were hospitalized in the multipurpose pediatric intensive care unit of the Abderrahim EL Harouchi children's hospital in Casablanca. The average age was 7.91 years, with extremes ranging from 18 months and 14 years and a male predominance of 75%. After a prodromal event, most often infectious (80%) and a free interval of 12 days on average, 2 types of motor disorders begin either hypo or arereflectic flaccid paralysis of the lower limbs (45.8%) or flaccid quadriplegia hypo or arereflectic (54.2%). During GBS, the most formidable complication is respiratory distress, which can occur at any time. In our study, respiratory impairment was observed in 70.8% of cases. In addition, other signs of severity, such as swallowing disorders (75%) and dysautonomic disorders (8.33%), were also observed, which justified care in the intensive care unit for all of our patients. The use of invasive ventilation was necessary in 76.5% of cases, and specific treatments based on immunoglobulins were administered in all our patients. Despite everything, the death rate remains high (25%) and is mainly due to complications related to hospitalization. Guillain Barré syndrome is, therefore, a pediatric emergency that requires rapid diagnosis and immediate assessment of severity criteria for the implementation of appropriate treatment.

Keywords: guillain barre syndrome, emergency, children, medical

Procedia PDF Downloads 54
285 Tool for Analysing the Sensitivity and Tolerance of Mechatronic Systems in Matlab GUI

Authors: Bohuslava Juhasova, Martin Juhas, Renata Masarova, Zuzana Sutova

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The article deals with the tool in Matlab GUI form that is designed to analyse a mechatronic system sensitivity and tolerance. In the analysed mechatronic system, a torque is transferred from the drive to the load through a coupling containing flexible elements. Different methods of control system design are used. The classic form of the feedback control is proposed using Naslin method, modulus optimum criterion and inverse dynamics method. The cascade form of the control is proposed based on combination of modulus optimum criterion and symmetric optimum criterion. The sensitivity is analysed on the basis of absolute and relative sensitivity of system function to the change of chosen parameter value of the mechatronic system, as well as the control subsystem. The tolerance is analysed in the form of determining the range of allowed relative changes of selected system parameters in the field of system stability. The tool allows to analyse an influence of torsion stiffness, torsion damping, inertia moments of the motor and the load and controller(s) parameters. The sensitivity and tolerance are monitored in terms of the impact of parameter change on the response in the form of system step response and system frequency-response logarithmic characteristics. The Symbolic Math Toolbox for expression of the final shape of analysed system functions was used. The sensitivity and tolerance are graphically represented as 2D graph of sensitivity or tolerance of the system function and 3D/2D static/interactive graph of step/frequency response.

Keywords: mechatronic systems, Matlab GUI, sensitivity, tolerance

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284 Parameters of Main Stage of Discharge between Artificial Charged Aerosol Cloud and Ground in Presence of Model Hydrometeor Arrays

Authors: D. S. Zhuravkova, A. G. Temnikov, O. S. Belova, L. L. Chernensky, T. K. Gerastenok, I. Y. Kalugina, N. Y. Lysov, A.V. Orlov

Abstract:

Investigation of the discharges from the artificial charged water aerosol clouds in presence of the arrays of the model hydrometeors could help to receive the new data about the peculiarities of the return stroke formation between the thundercloud and the ground when the large volumes of the hail particles participate in the lightning discharge initiation and propagation stimulation. Artificial charged water aerosol clouds of the negative or positive polarity with the potential up to one million volts have been used. Hail has been simulated by the group of the conductive model hydrometeors of the different form. Parameters of the impulse current of the main stage of the discharge between the artificial positively and negatively charged water aerosol clouds and the ground in presence of the model hydrometeors array and of its corresponding electromagnetic radiation have been determined. It was established that the parameters of the array of the model hydrometeors influence on the parameters of the main stage of the discharge between the artificial thundercloud cell and the ground. The maximal values of the main stage current impulse parameters and the electromagnetic radiation registered by the plate antennas have been found for the array of the model hydrometeors of the cylinder revolution form for the negatively charged aerosol cloud and for the array of the hydrometeors of the plate rhombus form for the positively charged aerosol cloud, correspondingly. It was found that parameters of the main stage of the discharge between the artificial charged water aerosol cloud and the ground in presence of the model hydrometeor array of the different considered forms depend on the polarity of the artificial charged aerosol cloud. In average, for all forms of the investigated model hydrometeors arrays, the values of the amplitude and the current rise of the main stage impulse current and the amplitude of the corresponding electromagnetic radiation for the artificial charged aerosol cloud of the positive polarity were in 1.1-1.9 times higher than for the charged aerosol cloud of the negative polarity. Thus, the received results could indicate to the possible more important role of the big volumes of the large hail arrays in the thundercloud on the parameters of the return stroke for the positive lightning.

Keywords: main stage of discharge, hydrometeor form, lightning parameters, negative and positive artificial charged aerosol cloud

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283 Eliciting and Confirming Data, Information, Knowledge and Wisdom in a Specialist Health Care Setting - The Wicked Method

Authors: Sinead Impey, Damon Berry, Selma Furtado, Miriam Galvin, Loretto Grogan, Orla Hardiman, Lucy Hederman, Mark Heverin, Vincent Wade, Linda Douris, Declan O'Sullivan, Gaye Stephens

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Healthcare is a knowledge-rich environment. This knowledge, while valuable, is not always accessible outside the borders of individual clinics. This research aims to address part of this problem (at a study site) by constructing a maximal data set (knowledge artefact) for motor neurone disease (MND). This data set is proposed as an initial knowledge base for a concurrent project to develop an MND patient data platform. It represents the domain knowledge at the study site for the duration of the research (12 months). A knowledge elicitation method was also developed from the lessons learned during this process - the WICKED method. WICKED is an anagram of the words: eliciting and confirming data, information, knowledge, wisdom. But it is also a reference to the concept of wicked problems, which are complex and challenging, as is eliciting expert knowledge. The method was evaluated at a second site, and benefits and limitations were noted. Benefits include that the method provided a systematic way to manage data, information, knowledge and wisdom (DIKW) from various sources, including healthcare specialists and existing data sets. Limitations surrounded the time required and how the data set produced only represents DIKW known during the research period. Future work is underway to address these limitations.

Keywords: healthcare, knowledge acquisition, maximal data sets, action design science

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282 Deficient Multisensory Integration with Concomitant Resting-State Connectivity in Adult Attention Deficit/Hyperactivity Disorder (ADHD)

Authors: Marcel Schulze, Behrem Aslan, Silke Lux, Alexandra Philipsen

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Objective: Patients with Attention Deficit/Hyperactivity Disorder (ADHD) often report that they are being flooded by sensory impressions. Studies investigating sensory processing show hypersensitivity for sensory inputs across the senses in children and adults with ADHD. Especially the auditory modality is affected by deficient acoustical inhibition and modulation of signals. While studying unimodal signal-processing is relevant and well-suited in a controlled laboratory environment, everyday life situations occur multimodal. A complex interplay of the senses is necessary to form a unified percept. In order to achieve this, the unimodal sensory modalities are bound together in a process called multisensory integration (MI). In the current study we investigate MI in an adult ADHD sample using the McGurk-effect – a well-known illusion where incongruent speech like phonemes lead in case of successful integration to a new perceived phoneme via late top-down attentional allocation . In ADHD neuronal dysregulation at rest e.g., aberrant within or between network functional connectivity may also account for difficulties in integrating across the senses. Therefore, the current study includes resting-state functional connectivity to investigate a possible relation of deficient network connectivity and the ability of stimulus integration. Method: Twenty-five ADHD patients (6 females, age: 30.08 (SD:9,3) years) and twenty-four healthy controls (9 females; age: 26.88 (SD: 6.3) years) were recruited. MI was examined using the McGurk effect, where - in case of successful MI - incongruent speech-like phonemes between visual and auditory modality are leading to a perception of a new phoneme. Mann-Whitney-U test was applied to assess statistical differences between groups. Echo-planar imaging-resting-state functional MRI was acquired on a 3.0 Tesla Siemens Magnetom MR scanner. A seed-to-voxel analysis was realized using the CONN toolbox. Results: Susceptibility to McGurk was significantly lowered for ADHD patients (ADHDMdn:5.83%, ControlsMdn:44.2%, U= 160.5, p=0.022, r=-0.34). When ADHD patients integrated phonemes, reaction times were significantly longer (ADHDMdn:1260ms, ControlsMdn:582ms, U=41.0, p<.000, r= -0.56). In functional connectivity medio temporal gyrus (seed) was negatively associated with primary auditory cortex, inferior frontal gyrus, precentral gyrus, and fusiform gyrus. Conclusion: MI seems to be deficient for ADHD patients for stimuli that need top-down attentional allocation. This finding is supported by stronger functional connectivity from unimodal sensory areas to polymodal, MI convergence zones for complex stimuli in ADHD patients.

Keywords: attention-deficit hyperactivity disorder, audiovisual integration, McGurk-effect, resting-state functional connectivity

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281 The Design of Smart Tactile Textiles for Therapeutic Applications

Authors: Karen Hong

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Smart tactile textiles are a series of textile-based products that incorporates smart embedded technology to be utilized as tactile therapeutic applications for 2 main groups of target users. The first group of users will be children with sensory processing disorder who are suffering from tactile sensory dysfunction. Children with tactile sensory issues may have difficulty tolerating the sensations generated from the touch of certain textures on the fabrics. A series of smart tactile textiles, collectively known as ‘Tactile Toys’ are developed as tactile therapy play objects, exposing children to different types of touch sensations within textiles, enabling them to enjoy tactile experiences together with interactive play which will help them to overcome fear of certain touch sensations. The second group of users will be the elderly or geriatric patients who are suffering from deteriorating sense of touch. One of the common consequences of aging is suffering from deteriorating sense of touch and a decline in motoric function. With the focus in stimulating the sense of touch for this particular group of end users, another series of smart tactile textiles, collectively known as ‘Tactile Aids’ are developed also as tactile therapy. This range of products can help to maintain touch sensitivity and at the same time allowing the elderly to enjoy interactive play to practice their hand-eye coordination and enhancing their motor skills. These smart tactile textile products are being designed and tested out by the end users and have proofed their efficacy as tactile therapy enabling the users to lead a better quality of life.

Keywords: smart textiles, embedded technology, tactile therapy, tactile aids, tactile toys

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280 Study of Motion of Impurity Ions in Poly(Vinylidene Fluoride) from View Point of Microstructure of Polymer Solid

Authors: Yuichi Anada

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Electrical properties of polymer solid is characterized by dielectric relaxation phenomenon. Complex permittivity shows a high dependence on frequency of external stimulation in the broad frequency range from 0.1mHz to 10GHz. The complex-permittivity dispersion gives us a lot of useful information about the molecular motion of polymers and the structure of polymer aggregates. However, the large dispersion of permittivity at low frequencies due to DC conduction of impurity ions often covers the dielectric relaxation in polymer solid. In experimental investigation, many researchers have tried to remove the DC conduction experimentally or analytically for a long time. On the other hand, our laboratory chose another way of research for this problem from the point of view of a reversal in thinking. The way of our research is to use the impurity ions in the DC conduction as a probe to detect the motion of polymer molecules and to investigate the structure of polymer aggregates. In addition to the complex permittivity, the electric modulus and the conductivity relaxation time are strong tools for investigating the ionic motion in DC conduction. In a non-crystalline part of melt-crystallized polymers, free spaces with inhomogeneous size exist between crystallites. As the impurity ions exist in the non-crystalline part and move through these inhomogeneous free spaces, the motion of ions reflects the microstructure of non-crystalline part. The ionic motion of impurity ions in poly(vinylidene fluoride) (PVDF) is investigated in this study. Frequency dependence of the loss permittivity of PVDF shows a characteristic of the direct current (DC) conduction below 1 kHz of frequency at 435 K. The electric modulus-frequency curve shows a characteristic of the dispersion with the single conductivity relaxation time. Namely, it is the Debye-type dispersion. The conductivity relaxation time analyzed from this curve is 0.00003 s at 435 K. From the plot of conductivity relaxation time of PVDF together with the other polymers against permittivity, it was found that there are two group of polymers; one of the group is characterized by small conductivity relaxation time and large permittivity, and another is characterized by large conductivity relaxation time and small permittivity.

Keywords: conductivity relaxation time, electric modulus, ionic motion, permittivity, poly(vinylidene fluoride), DC conduction

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279 Identification and Molecular Profiling of A Family I Cystatin Homologue from Sebastes schlegeli Deciphering Its Putative Role in Host Immunity

Authors: Don Anushka Sandaruwan Elvitigala, P. D. S. U. Wickramasinghe, Jehee Lee

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Cystatins are a large superfamily of proteins which act as reversible inhibitors of cysteine proteases. Papain proteases and cysteine cathepsins are predominant substrates of cystatins. Cystatin superfamily can be further clustered into three groups as Stefins, Cystatins, and Kininogens. Among them, stefines are also known as family 1 cystatins which harbors cystatin Bs and cystatin As. In this study, a homologue of family one cystatins more close to cystatin Bs was identified from Korean black rockfish (Sebastes schlegeli) using a prior constructed cDNA (complementary deoxyribonucleic acid) database and designated as RfCyt1. The full-length cDNA of RfCyt1 consisted of 573 bp, with a coding region of 294 bp. It comprised a 5´-untranslated region (UTR) of 55 bp, and 3´-UTR of 263 bp. The coding sequence encodes a polypeptide consisting of 97 amino acids with a predicted molecular weight of 11kDa and theoretical isoelectric point of 6.3. The RfCyt1 shared homology with other teleosts and vertebrate species and consisted conserved features of cystatin family signature including single cystatin-like domain, cysteine protease inhibitory signature of pentapeptide (QXVXG) consensus sequence and N-terminal two conserved neighboring glycine (⁸GG⁹) residues. As expected, phylogenetic reconstruction developed using the neighbor-joining method showed that RfCyt1 is clustered with the cystatin family 1 members, in which more closely with its teleostan orthologues. An SYBR Green qPCR (quantitative polymerase chain reaction) assay was performed to quantify the RfCytB transcripts in different tissues in healthy and immune stimulated fish. RfCyt1 was ubiquitously expressed in all tissue types of healthy animals with gill and spleen being the highest. Temporal expression of RfCyt1 displayed significant up-regulation upon infection with Aeromonas salmonicida. Recombinantly expressed RfCyt1 showed concentration-dependent papain inhibitory activity. Collectively these findings evidence for detectable protease inhibitory and immunity relevant roles of RfCyt1 in Sebastes schlegeli.

Keywords: Sebastes schlegeli, family 1 cystatin, immune stimulation, expressional modulation

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278 A 3D Bioprinting System for Engineering Cell-Embedded Hydrogels by Digital Light Processing

Authors: Jimmy Jiun-Ming Su, Yuan-Min Lin

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Bioprinting has been applied to produce 3D cellular constructs for tissue engineering. Microextrusion printing is the most common used method. However, printing low viscosity bioink is a challenge for this method. Herein, we developed a new 3D printing system to fabricate cell-laden hydrogels via a DLP-based projector. The bioprinter is assembled from affordable equipment including a stepper motor, screw, LED-based DLP projector, open source computer hardware and software. The system can use low viscosity and photo-polymerized bioink to fabricate 3D tissue mimics in a layer-by-layer manner. In this study, we used gelatin methylacrylate (GelMA) as bioink for stem cell encapsulation. In order to reinforce the printed construct, surface modified hydroxyapatite has been added in the bioink. We demonstrated the silanization of hydroxyapatite could improve the crosslinking between the interface of hydroxyapatite and GelMA. The results showed that the incorporation of silanized hydroxyapatite into the bioink had an enhancing effect on the mechanical properties of printed hydrogel, in addition, the hydrogel had low cytotoxicity and promoted the differentiation of embedded human bone marrow stem cells (hBMSCs) and retinal pigment epithelium (RPE) cells. Moreover, this bioprinting system has the ability to generate microchannels inside the engineered tissues to facilitate diffusion of nutrients. We believe this 3D bioprinting system has potential to fabricate various tissues for clinical applications and regenerative medicine in the future.

Keywords: bioprinting, cell encapsulation, digital light processing, GelMA hydrogel

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277 Multicellular Cancer Spheroids as an in Vitro Model for Localized Hyperthermia Study

Authors: Kamila Dus-Szachniewicz, Artur Bednarkiewicz, Katarzyna Gdesz-Birula, Slawomir Drobczynski

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In modern oncology hyperthermia (HT) is defined as a controlled tumor heating. HT treatment temperatures range between 40–48 °C and can selectively damage heat-sensitive cancer cells or limit their further growth, usually with minimal injury to healthy tissues. Despite many advantages, conventional whole-body and regional hyperthermia have clinically relevant side effects, including cardiac and vascular disorders. Additionally, the lack of accessibility of deep-seated tumor sites and impaired targeting micrometastases renders HT less effective. It is believed that above disadvantages can significantly overcome by the application of biofunctionalized microparticles, which can specifically target tumor sites and become activated by an external stimulus to provide a sufficient cellular response. In our research, the unique optical tweezers system have enabled capturing the silica microparticles, primary cells and tumor spheroids in highly controllable and reproducible environment to study the impact of localized heat stimulation on normal and pathological cell and within multicellular tumor spheroid. High throughput spheroid model was introduced to better mimic the response to HT treatment on tumors in vivo. Additionally, application of local heating of tumor spheroids was performed in strictly controlled conditions resembling tumor microenvironment (temperature, pH, hypoxia, etc.), in response to localized and nonhomogeneous hyperthermia in the extracellular matrix, which promotes tumor progression and metastatic spread. The lack of precise control over these well- defined parameters in basic research leads to discrepancies in the response of tumor cells to the new treatment strategy in preclinical animal testing. The developed approach enables also sorting out subclasses of cells, which exhibit partial or total resistance to therapy, in order to understand fundamental aspects of the resistance shown by given tumor cells in response to given therapy mode and conditions. This work was funded by the National Science Centre (NCN, Poland) under grant no. UMO-2017/27/B/ST7/01255.

Keywords: cancer spheroids, hyperthermia, microparticles, optical tweezers

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276 Metformin and Its Combination with Sodium Hydrosulfide Influences Plasma Galectin-3 and CSE/H₂S System in Diabetic Rat's Heart

Authors: I. V. Palamarchuk, N. V. Zaichko

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Background and Aims: Galectin-3 is a marker of subclinical cardiac injury and is elevated in individuals with type 2 diabetes mellitus; while hydrogen sulfide (H₂S), metabolite of sulfur-containing amino acids, is considered having antifibrogenic effects. This study was designed to investigate whether metformin and its combination with NaHS can influence plasma galectin-3 and cystathionine-γ-lyase/hydrogen sulfide (CSE/H₂S) system in diabetic rat’s heart. Methods: 32 healthy male rats (180-250 g) were divided into 4 groups. To induct diabetes, rats (group 2-4) were injected with streptozotocin (STZ, 40 mg/kg/i.p., 0.1 M citrate buffer (pH 4.5). Rats from 3d (STZ+Metf) and 4th (STZ+Metf+NaHS) groups were given metformin (500 mg/kg/day) orally, and rats from 4th (STZ+Metf+NaHS) group were injected sodium hydrosulfide (NaHS, 3 mg/kg/i.p.) once per day starting from 3 to 28 day after streptozotocin injection. Rats of first group (control) were administered the equivalent volumes of 0.9% NaCl. Plasma galectin-3 was measured by ELISA. Rats’ hearts were sampled for determination of H2S by reaction with N,N-Dimethyl-p-phenylenediamine. Determination of CSE gene expression was performed in real time using PCR in the presence of SYBR Green I, using DT-Light detecting amplifier ('DNA-technology', Russia). Results: Induction of streptozotocin diabetes (STZ-diabetes, group 2) was followed by low myocardial H2S concentration and CSE expression (by 35%, p < 0.05 and 60.5%, p < 0.001 respectively, than that in controls), while plasma galectin-3 in this group was significantly higher than in controls (by 3.8 times, p < 0.05). Administration of metformin (group 3) resulted in significantly higher H₂S concentration (by 28.5%, p < 0.05), whereas CSE expression was only by 6% more than that in STZ-diabetes, as well as plasma galectin-3 was only by 14.8% lower in comparison with untreated diabetic rats. The inhibition of H₂S generation and CSE activity by diabetes was greatly attenuated in STZ+Metf+NaHS group. The combination of metformin with NaHS significantly stimulated H₂S production (by 48%, p < 0.05 and 15%, p < 0.05 more than STZ-diabetes and STZ+Metf respectively) and CSE gene expression (by 64.8%, p < 0.05 compared to STZ-diabetes and by 55.4%,p < 0.05 compared to STZ+Metf). Besides, plasma galectin-3 in rats receiving metformin and NaHS was significantly lower by 42%, p < 0.05 and 32.5%, p < 0.05 compared to STZ-diabetes and STZ+Metf groups respectively. Conclusions: To summarize, dysfunction of CSE/H2S system and galectin-3 stimulation was found in streptozotocin-induced diabetic rats. Metformin and its combination with exogenous H2S effectively prevented the development of metabolic changes induced by diabetes. These findings suggest that CSE/H₂S system can be integrated into pathogenesis of diabetic complications through modulation of pro-inflammatory and pro-fibrogenic mediator galectin-3.

Keywords: cystathionine-γ-lyase, diabetic heart, galectin-3, hydrogen sulfide, metformin, sodium hydrosulfide

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275 Survey of the Relationship between Functional Movement Screening Tests and Anthropometric Dimensions in Healthy People, 2018

Authors: Akram Sadat Jafari Roodbandi, Parisa Kahani, Fatollah Rahimi Bafrani, Ali Dehghan, Nava Seyedi, Vafa Feyzi, Zohreh Forozanfar

Abstract:

Introduction: Movement function is considered as the ability to produce and maintain balance, stability, and movement throughout the movement chain. Having a score of 14 and above on 7 sub-tests in the functional movement screening (FMS) test shows agility and optimal movement performance. On the other hand, the person's body is an important factor in physical fitness and optimal movement performance. The aim of this study was to identify effective anthropometric dimensions in increasing motor function. Methods: This study was a descriptive-analytical and cross-sectional study using simple random sampling. FMS test and 25 anthropometric dimensions and subcutaneous in five body regions measured in 139 healthy students of Bam University of Medical Sciences. Data analysis was performed using SPSS software and univariate tests and linear regressions at a significance level of 0.05. Results: 139 students were enrolled in the study, 51.1% (71 subjects) and the rest were female. The mean and standard deviation of age, weight, height, and arm subcutaneous fat were 21.5 ± 1.45, 12.6 ± 64.3, 168.7 ± 9.8, 15.3 ± 7, respectively. 17 subjects (12.2%) of the participants in the study have a score of less than 14, and the rest were above 14. Using regression analysis, it was found that exercise and arm subcutaneous fat are predictive variables associated with obtaining a high score in the FMS test. Conclusion: Exercise and weight loss are effective factors for increasing the movement performance of individuals, and this factor is independent of the size of other physical dimensions.

Keywords: functional movement, screening test, anthropometry, ergonomics

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274 Event-Related Potentials and Behavioral Reactions during Native and Foreign Languages Comprehension in Bilingual Inhabitants of Siberia

Authors: Tatiana N. Astakhova, Alexander E. Saprygin, Tatyana A. Golovko, Alexander N. Savostyanov, Mikhail S. Vlasov, Natalia V. Borisova, Alexandera G. Karpova, Urana N. Kavai-ool, Elena D. Mokur-ool, Nikolay A. Kolchanov, Lubomir I. Aftanas

Abstract:

The study is dedicated to the research of brain activity in bilingual inhabitants of Siberia. We compared behavioral reactions and event-related potentials in Turkic-speaking inhabitants of Siberia (Tuvinians and Yakuts) and Russians. 63 healthy aboriginals of the Tyva Republic, 29 inhabitants of the Sakha (Yakutia) Republic, and 55 Russians from Novosibirsk participated in the study. All the healthy and right-handed participants, matched on age and sex, were students of different universities. EEG’s were recorded during the solving of linguistic tasks. In these tasks, participants had to find a syntax error in the written sentences. There were four groups of sentences: Russian, English, Tuvinian, and Yakut. All participants completed the tasks in Russian and English. Additionally, Tuvinians and Yakuts completed the tasks in Tuvinian or Yakut respectively. For Russians, EEG's were recorded using 128-channels according to the extended International 10-10 system, and the signals were amplified using “Neuroscan (USA)” amplifiers. For Tuvinians and Yakuts, EEG's were recorded using 64-channels and amplifiers Brain Products, Germany. In all groups, 0.3-100 Hz analog filtering and sampling rate 1000 Hz were used. As parameters of behavioral reactions, response speed and the accuracy of recognition were used. Event-related potentials (ERP) responses P300 and P600 were used as indicators of brain activity. The behavioral reactions showed that in Russians, the response speed for Russian was faster than for English. Also, the accuracy of solving tasks was higher for Russian than for English. The peak P300 in Russians were higher for English, the peak P600 in the left temporal cortex were higher for the Russian language. Both Tuvinians and Yakuts have no difference in accuracy of solving tasks in Russian and in their respective national languages. However, the response speed was faster for tasks in Russian than for tasks in their national language. Tuvinians and Yakuts showed bad accuracy in English, but the response speed was higher for English than for Russian and the national languages. This can be explained by the fact that they did not think carefully and gave a random answer for English. In Tuvinians, The P300 and P600 amplitudes and cortical topology were the same for Russian and Tuvinian and different for English. In Yakuts, the P300 and P600 amplitudes and topology of ERP for Russian were the same as what Russians had for Russian. In Yakuts, brain reactions during Yakut and English comprehension had no difference, and were reflected to foreign language comprehension - while the Russian language comprehension was reflected to native language comprehension. We found out that the Tuvinians recognized both Russian and Tuvinian as native languages, and English as a foreign language. The Yakuts recognized both English and Yakut as a foreign language, and only Russian as a native language. According to the inquirer, both Tuvinians and Yakuts use the national language as a spoken language, whereas they don’t use it for writing. It can well be a reason that Yakuts perceive the Yakut writing language as a foreign language while writing Russian as their native.

Keywords: EEG, ERP, native and foreign languages comprehension, Siberian inhabitants

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273 Effectiveness of Cognitive and Supportive-Expressive Group Therapies on Self-Efficiency and Life Style in MS Patients

Authors: Kamran Yazdanbakhsh, Somayeh Mahmoudi

Abstract:

Multiple sclerosis is the most common chronic disease of the central nervous system associated with demyelination of neurons and several demyelinated parts of the disease encompasses throughout the white matter and affects the sensory and motor function. This study compared the effectiveness of two methods of cognitive therapy and supportive-expressive therapy on the efficacy and quality of life in MS patients. This is an experimental project which has used developed group pretest - posttest and follow-up with 3 groups. The study included all patients with multiple sclerosis in 2013 that were members of the MS Society of Iran in Tehran. The sample included 45 patients with MS that were selected volunteerily of members of the MS society of Iran and randomly divided into three groups and pretest, posttest, and follow-up (three months) for the three groups had been done.The dimensions of quality of life in patients with multiple sclerosis scale, and general self-efficiency scale of Schwarzer and Jerusalem was used for collecting data. The results showed that there was a significant difference between the mean of quality of life scores at pretest, posttest, and follow-up of the experimental groups. There was no significant difference between the mean of quality of life of the experimental groups which means that both groups were effective and had the same effect. There was no significant difference between the mean of self-efficiency scores in control and experimental group in pretest, posttest and follow-up. Thus, by using cognitive and supportive-expressive group therapy we can improve quality of life in MS patients and make great strides in their mental health.

Keywords: cognitive group therapy, life style, MS, self-efficiency, supportive-expressive group therapy

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272 Testing the Possibility of Healthy Individuals to Mimic Fatigability in Multiple Sclerotic Patients

Authors: Emmanuel Abban Sagoe

Abstract:

A proper functioning of the Central Nervous System ensures that we are able to accomplish just about everything we do as human beings such as walking, breathing, running, etc. Myelinated neurons throughout the body which transmit signals at high speeds facilitate these actions. In the case of MS, the body’s immune system attacks the myelin sheath surrounding the neurons and overtime destroys the myelin sheaths. Depending upon where the destruction occurs in the brain symptoms can vary from person to person. Fatigue is, however, the biggest problem encountered by an MS sufferer. It is very often described as the bedrock upon which other symptoms of MS such challenges in balance and coordination, dizziness, slurred speech, etc. may occur. Classifying and distinguishing between perceptions based fatigue and performance based fatigability is key to identifying appropriate treatment options for patients. Objective methods for assessing motor fatigability is also key to providing clinicians and physiotherapist with critical information on the progression of the symptom. This study tested if the Fatigue Index Kliniken Schmieder assessment tool can detect fatigability as seen in MS patients when healthy subjects with no known history of neurological pathology mimic abnormal gaits. Thirty three healthy adults between ages 18-58years volunteered as subjects for the study. The subjects, strapped with RehaWatch sensors on both feet, completed 6 gait protocols of normal and mimicked fatigable gaits for 60 seconds per each gait and at 1.38889m/s treadmill speed following clear instructions given.

Keywords: attractor attributes, fatigue index Kliniken Schmieder, gait variability, movement pattern

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271 Numerical Study on the Flow around a Steadily Rotating Spring: Understanding the Propulsion of a Bacterial Flagellum

Authors: Won Yeol Choi, Sangmo Kang

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The propulsion of a bacterial flagellum in a viscous fluid has attracted many interests in the field of biological hydrodynamics, but remains yet fully understood and thus still a challenging problem. In this study, therefore, we have numerically investigated the flow around a steadily rotating micro-sized spring to further understand such bacterial flagellum propulsion. Note that a bacterium gains thrust (propulsive force) by rotating the flagellum connected to the body through a bio motor to move forward. For the investigation, we convert the spring model from the micro scale to the macro scale using a similitude law (scale law) and perform simulations on the converted macro-scale model using a commercial software package, CFX v13 (ANSYS). To scrutinize the propulsion characteristics of the flagellum through the simulations, we make parameter studies by changing some flow parameters, such as the pitch, helical radius and rotational speed of the spring and the Reynolds number (or fluid viscosity), expected to affect the thrust force experienced by the rotating spring. Results show that the propulsion characteristics depend strongly on the parameters mentioned above. It is observed that the forward thrust increases in a linear fashion with either of the rotational speed or the fluid viscosity. In addition, the thrust is directly proportional to square of the helical radius and but the thrust force is increased and then decreased based on the peak value to the pitch. Finally, we also present the appropriate flow and pressure fields visualized to support the observations.

Keywords: fluid viscosity, hydrodynamics, similitude, propulsive force

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270 Vibration Analysis of Magnetostrictive Nano-Plate by Using Modified Couple Stress and Nonlocal Elasticity Theories

Authors: Hamed Khani Arani, Mohammad Shariyat, Armaghan Mohammadian

Abstract:

In the present study, the free vibration of magnetostrictive nano-plate (MsNP) resting on the Pasternak foundation is investigated. Firstly, the modified couple stress (MCS) and nonlocal elasticity theories are compared together and taken into account to consider the small scale effects; in this paper not only two theories are analyzed but also it improves the MCS theory is more accurate than nonlocal elasticity theory in such problems. A feedback control system is utilized to investigate the effects of a magnetic field. First-order shear deformation theory (FSDT), Hamilton’s principle and energy method are utilized in order to drive the equations of motion and these equations are solved by differential quadrature method (DQM) for simply supported boundary conditions. The MsNP undergoes in-plane forces in x and y directions. In this regard, the dimensionless frequency is plotted to study the effects of small scale parameter, magnetic field, aspect ratio, thickness ratio and compression and tension loads. Results indicate that these parameters play a key role on the natural frequency. According to the above results, MsNP can be used in the communications equipment, smart control vibration of nanostructure especially in sensor and actuators such as wireless linear micro motor and smart nano valves in injectors.

Keywords: feedback control system, magnetostrictive nano-plate, modified couple stress theory, nonlocal elasticity theory, vibration analysis

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269 Integrating Circular Economy Framework into Life Cycle Analysis: An Exploratory Study Applied to Geothermal Power Generation Technologies

Authors: Jingyi Li, Laurence Stamford, Alejandro Gallego-Schmid

Abstract:

Renewable electricity has become an indispensable contributor to achieving net-zero by the mid-century to tackle climate change. Unlike solar, wind, or hydro, geothermal was stagnant in its electricity production development for decades. However, with the significant breakthrough made in recent years, especially the implementation of enhanced geothermal systems (EGS) in various regions globally, geothermal electricity could play a pivotal role in alleviating greenhouse gas emissions. Life cycle assessment has been applied to analyze specific geothermal power generation technologies, which proposed suggestions to optimize its environmental performance. For instance, selecting a high heat gradient region enables a higher flow rate from the production well and extends the technical lifespan. Although such process-level improvements have been made, the significance of geothermal power generation technologies so far has not explicitly displayed its competitiveness on a broader horizon. Therefore, this review-based study integrates a circular economy framework into life cycle assessment, clarifying the underlying added values for geothermal power plants to complete the sustainability profile. The derived results have provided an enlarged platform to discuss geothermal power generation technologies: (i) recover the heat and electricity from the process to reduce the fossil fuel requirements; (ii) recycle the construction materials, such as copper, steel, and aluminum for future projects; (iii) extract the lithium ions from geothermal brine and make geothermal reservoir become a potential supplier of the lithium battery industry; (iv) repurpose the abandoned oil and gas wells to build geothermal power plants; (v) integrate geothermal energy with other available renewable energies (e.g., solar and wind) to provide heat and electricity as a hybrid system at different weather; (vi) rethink the fluids used in stimulation process (EGS only), replace water with CO2 to achieve negative emissions from the system. These results provided a new perspective to the researchers, investors, and policymakers to rethink the role of geothermal in the energy supply network.

Keywords: climate, renewable energy, R strategies, sustainability

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268 Rear Seat Belt Use in Developing Countries: A Case Study from the United Arab Emirates

Authors: Salaheddine Bendak, Sara S. Alnaqbi

Abstract:

The seat belt is a vital tool in improving traffic safety conditions and minimising injuries due to traffic accidents. Most developing countries are facing a big problems associated with the human and financial losses due to traffic accidents. One way to minimise these losses is the use of seat belts by passengers both in the front and rear seats of a vehicle; however, at the same time, close to nothing is known about the rates of seat belt utilisation among rear seat passengers in many developing countries. Therefore, there is a need to estimate these rates in order to know the extent of this problem and how people interact with traffic safety measures like seat belts and find demographic characteristics that contribute to wearing or non-wearing of seat belts with the aim of finding solutions to improve wearing rates. In this paper, an observational study was done to gather data on restraints use in motor vehicle rear seats in eight observational stations in a rapidly developing country, the United Arab Emirates (UAE), and estimate a use rate for the whole country. Also, a questionnaire was used in order to study demographic characteristics affecting the wearing of seatbelts in rear seats. Results of the observational study showed that the overall wearing/usage rate was 12.3%, which is considered very low when compared to other countries. Survey results show that single, male, less educated passengers from Arab and South Asian backgrounds use seat belts reportedly less than others. Finally, solutions are put forward to improve this wearing rate based on the results of this study.

Keywords: Seat belts, traffic crashes, United Arab Emirates, rear seats

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267 Design Study on a Contactless Material Feeding Device for Electro Conductive Workpieces

Authors: Oliver Commichau, Richard Krimm, Bernd-Arno Behrens

Abstract:

A growing demand on the production rate of modern presses leads to higher stroke rates. Commonly used material feeding devices for presses like grippers and roll-feeding systems can only achieve high stroke rates along with high gripper forces, to avoid stick-slip. These forces are limited by the sensibility of the surfaces of the workpieces. Stick-slip leads to scratches on the surface and false positioning of the workpiece. In this paper, a new contactless feeding device is presented, which develops higher feeding force without damaging the surface of the workpiece through gripping forces. It is based on the principle of the linear induction motor. A primary part creates a magnetic field and induces eddy currents in the electrically conductive material. A Lorentz-Force applies to the workpiece in feeding direction as a mutual reaction between the eddy-currents and the magnetic induction. In this study, the FEA model of this approach is shown. The calculation of this model was used to identify the influence of various design parameters on the performance of the feeder and thus showing the promising capabilities and limits of this technology. In order to validate the study, a prototype of the feeding device has been built. An experimental setup was used to measure pulling forces and placement accuracy of the experimental feeder in order to give an outlook of a potential industrial application of this approach.

Keywords: conductive material, contactless feeding, linear induction, Lorentz-Force

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266 Comparison of Mini-BESTest versus Berg Balance Scale to Evaluate Balance Disorders in Parkinson's Disease

Authors: R. Harihara Prakash, Shweta R. Parikh, Sangna S. Sheth

Abstract:

The purpose of this study was to explore the usefulness of the Mini-BESTest compared to the Berg Balance Scale in evaluating balance in people with Parkinson's Disease (PD) of varying severity. Evaluation were done to obtain (1) the distribution of patients scores to look for ceiling effects, (2) concurrent validity with severity of disease, and (3) the sensitivity & specificity of separating people with or without postural response deficits. Methods and Material: Seventy-seven(77) people with Parkinson's Disease were tested for balance deficits using the Berg Balance Scale, Mini-BESTest. Unified Parkinson’s Disease Rating Scale (UPDRS) III and the Hoehn & Yahr (H&Y) disease severity scales were used for classification. Materials used in this study were case record sheet, chair without arm rests or wheels, Incline ramp, stopwatch, a box, 3 meter distance measured out and marked on the floor with tape [from chair]. Statistical analysis used: Multiple Linear regression was carried out of UPDRS jointly on the two scores for the Berg and Mini-BESTest. Receiver operating characteristic curves for classifying people into two groups based on a threshold for the H&Y score, to discriminate between mild PD versus more severe PD.Correlation co-efficient to find relativeness between the two variables. Results: The Mini-BESTest is highly correlated with the Berg (r = 0.732,P < 0.001), but avoids the ceiling compression effect of the Berg for mild PD (skewness −0.714 Berg, −0.512 Mini-BESTest). Consequently, the Mini-BESTest is more effective than the Berg for predicting UPDRS Motor score (P < 0.001 Mini-BESTest versus P = 0.72 Berg), and for discriminating between those with and without postural response deficits as measured by the H&Y (ROC).

Keywords: balance, berg balance scale, MINI BESTest, parkinson's disease

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265 Isolation, Characterization, and Antibacterial Evaluation of Antimicrobial Peptides and Derivatives from Fly Larvae Sarconesiopsis magellanica (Diptera: Calliphoridae)

Authors: A. Díaz-Roa, P. I. Silva Junior, F. J. Bello

Abstract:

Sarconesiopsis magellanica (Diptera: Calliphoridae) is a medically important necrophagous fly which is used for establishing the post-mortem interval. Dipterous maggots release diverse proteins and peptides contained in larval excretion and secretion (ES) products playing a key role in digestion. The most important mechanism for combating infection using larval therapy depends on larval ES. These larvae are protected against infection by a diverse spectrum of antimicrobial peptides (AMPs), one already known like lucifensin. Special interest in these peptides has also been aroused regarding understanding their role in wound healing since they degrade necrotic tissue and kill different bacteria during larval therapy. The action of larvae on wounds occurs through 3 mechanisms of action: removal of necrotic tissue, stimulation of granulation tissue, and antibacterial action of larval ES. Some components of the ES include calcium, urea, allantoin ammonium bicarbonate and reducing the viability of Gram positive and Gram negative bacteria. The Lucilia sericata fly larvae have been the most used, however, we need to evaluate new species that could potentially be similar or more effective than fly above. This study was thus aimed at identifying and characterizing S. magellanica AMPs contained in ES products for the first time and compared them with the common fly used L. sericata. These products were obtained from third-instar larvae taken from a previously established colony. For the first analysis, ES fractions were separate by Sep-Pak C18 disposable columns (first step). The material obtained was fractionated by RP-HPLC by using Júpiter C18 semi-preparative column. The products were then lyophilized and their antimicrobial activity was characterized by incubation with different bacterial strains. The first chromatographic analysis of ES from L. sericata gives 6 fractions with antimicrobial activity against Gram-positive bacteria Micrococus luteus, and 3 fractions with activity against Gram-negative bacteria Pseudomonae aeruginosa while the one from S. magellanica gaves 1 fraction against M. luteus and 4 against P. aeruginosa. Maybe one of these fractions could correspond to the peptide already known from L. sericata. These results show the first work for supporting further experiments aimed at validating S. magellanica use in larval therapy. We still need to search if we find some new molecules, by making mass spectrometry and ‘de novo sequencing’. Further studies are necessary to identify and characterize them to better understand their functioning.

Keywords: antimicrobial peptides, larval therapy, Lucilia sericata, Sarconesiopsis magellanica

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264 The Quantitative Optical Modulation of Dopamine Receptor-Mediated Endocytosis Using an Optogenetic System

Authors: Qiaoyue Kuang, Yang Li, Mizuki Endo, Takeaki Ozawa

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G protein-coupled receptors (GPCR) are the largest family of receptor proteins that detect molecules outside the cell and activate cellular responses. Of the GPCRs, dopamine receptors, which recognize extracellular dopamine, are essential to mammals due to their roles in numerous physiological events, including autonomic movement, hormonal regulation, emotions, and the reward system in the brain. To precisely understand the physiological roles of dopamine receptors, it is important to spatiotemporally control the signaling mediated by dopamine receptors, which is strongly dependent on their surface expression. Conventionally, chemical-induced interactions were applied to trigger the endocytosis of cell surface receptors. However, these methods were subjected to diffusion and therefore lacked temporal and special precision. To further understand the receptor-mediated signaling and to control the plasma membrane expression of receptors, an optogenetic tool called E-fragment was developed. The C-terminus of a light-sensitive photosensory protein cyptochrome2 (CRY2) was attached to β-Arrestin, and the E-fragment was generated by fusing the C-terminal peptide of vasopressin receptor (V2R) to CRY2’s binding partner protein CIB. The CRY2-CIB heterodimerization triggered by blue light stimulation brings β-Arrestin to the vicinity of membrane receptors and results in receptor endocytosis. In this study, the E-fragment system was applied to dopamine receptors 1 and 2 (DRD1 and DRD2) to control dopamine signaling. First, confocal fluorescence microscope observation qualitatively confirmed the light-induced endocytosis of E-fragment fused receptors. Second, NanoBiT bioluminescence assay verified quantitatively that the surface amount of E-fragment labeled receptors decreased after light treatment. Finally, GloSensor bioluminescence assay results suggested that the E-fragment-dependent receptor light-induced endocytosis decreased cAMP production in DRD1 signaling and attenuated the inhibition effect of DRD2 on cAMP production. The developed optogenetic tool was able to induce receptor endocytosis by external light, providing opportunities to further understand numerous physiological activities by controlling receptor-mediated signaling spatiotemporally.

Keywords: dopamine receptors, endocytosis, G protein-coupled receptors, optogenetics

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263 Screening for Non-hallucinogenic Neuroplastogens as Drug Candidates for the Treatment of Anxiety, Depression, and Posttraumatic Stress Disorder

Authors: Jillian M. Hagel, Joseph E. Tucker, Peter J. Facchini

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With the aim of establishing a holistic approach for the treatment of central nervous system (CNS) disorders, we are pursuing a drug development program rapidly progressing through discovery and characterization phases. The drug candidates identified in this program are referred to as neuroplastogens owing to their ability to mediate neuroplasticity, which can be beneficial to patients suffering from anxiety, depression, or posttraumatic stress disorder. These and other related neuropsychiatric conditions are associated with the onset of neuronal atrophy, which is defined as a reduction in the number and/or productivity of neurons. The stimulation of neuroplasticity results in an increase in the connectivity between neurons and promotes the restoration of healthy brain function. We have synthesized a substantial catalogue of proprietary indolethylamine derivatives based on the general structures of serotonin (5-hydroxytryptamine) and psychedelic molecules such as N,N-dimethyltryptamine (DMT) and psilocin (4-hydroxy-DMT) that function as neuroplastogens. A primary objective in our screening protocol is the identification of derivatives associated with a significant reduction in hallucination, which will allow administration of the drug at a dose that induces neuroplasticity and triggers other efficacious outcomes in the treatment of targeted CNS disorders but which does not cause a psychedelic response in the patient. Both neuroplasticity and hallucination are associated with engagement of the 5HT2A receptor, requiring drug candidates differentially coupled to these two outcomes at a molecular level. We use novel and proprietary artificial intelligence algorithms to predict the mode of binding to the 5HT2A receptor, which has been shown to correlate with the hallucinogenic response. Hallucination is tested using the mouse head-twitch response model, whereas mouse marble-burying and sucrose preference assays are used to evaluate anxiolytic and anti-depressive potential. Neuroplasticity is assays using dendritic outgrowth assays and cell-based ELISA analysis. Pharmacokinetics and additional receptor-binding analyses also contribute the selection of lead candidates. A summary of the program is presented.

Keywords: neuroplastogen, non-hallucinogenic, drug development, anxiety, depression, PTSD, indolethylamine derivatives, psychedelic-inspired, 5-HT2A receptor, computational chemistry, head-twitch response behavioural model, neurite outgrowth assay

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262 CAP-Glycine Protein Governs Growth, Differentiation, and the Pathogenicity of Global Meningoencephalitis Fungi

Authors: Kyung-Tae Lee, Li Li Wang, Kwang-Woo Jung, Yong-Sun Bahn

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Microtubules are involved in mechanical support, cytoplasmic organization as well as in a number of cellular processes by interacting with diverse microtubule-associated proteins (MAPs), such as plus-end tracking proteins, motor proteins, and tubulin-folding cofactors. A common feature of these proteins is the presence of a cytoskeleton-associated protein-glycine-rich (CAP-Gly) domain, which is evolutionarily conserved and generally considered to bind to α-tubulin to regulate functions of microtubules. However, there has been a dearth of research on CAP-Gly proteins in fungal pathogens, including Cryptococcus neoformans, which causes fatal meningoencephalitis globally. In this study, we identified five CAP-Gly proteins encoding genes in C. neoformans. Among these, Cgp1, encoded by CNAG_06352, has a unique domain structure that has not been reported before in other eukaryotes. Supporting the role of Cpg1 in microtubule-related functions, we demonstrate that deletion or overexpression of CGP1 alters cellular susceptibility to thiabendazole, a microtubule destabilizer, and Cgp1 is co-localized with cytoplasmic microtubules. Related to the cellular functions of microtubules, Cgp1 also governs maintenance of membrane stability and genotoxic stress responses. Furthermore, we demonstrate that Cgp1 uniquely regulates sexual differentiation of C. neoformans with distinct roles in the early and late stage of mating. Our domain analysis reveals that the CAP-Gly domain plays major roles in all the functions of Cgp1. Finally, the cgp1Δ mutant is attenuated in virulence. In conclusion, this novel CAP-Gly protein, Cgp1, has pleotropic roles in regulating growth, stress responses, differentiation and pathogenicity of C. neoformans.

Keywords: human fungal pathogen, CAP-Glycine protein, microtubule, meningoencephalitis

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261 Structural and Functional Correlates of Reaction Time Variability in a Large Sample of Healthy Adolescents and Adolescents with ADHD Symptoms

Authors: Laura O’Halloran, Zhipeng Cao, Clare M. Kelly, Hugh Garavan, Robert Whelan

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Reaction time (RT) variability on cognitive tasks provides the index of the efficiency of executive control processes (e.g. attention and inhibitory control) and is considered to be a hallmark of clinical disorders, such as attention-deficit disorder (ADHD). Increased RT variability is associated with structural and functional brain differences in children and adults with various clinical disorders, as well as poorer task performance accuracy. Furthermore, the strength of functional connectivity across various brain networks, such as the negative relationship between the task-negative default mode network and task-positive attentional networks, has been found to reflect differences in RT variability. Although RT variability may provide an index of attentional efficiency, as well as being a useful indicator of neurological impairment, the brain substrates associated with RT variability remain relatively poorly defined, particularly in a healthy sample. Method: Firstly, we used the intra-individual coefficient of variation (ICV) as an index of RT variability from “Go” responses on the Stop Signal Task. We then examined the functional and structural neural correlates of ICV in a large sample of 14-year old healthy adolescents (n=1719). Of these, a subset had elevated symptoms of ADHD (n=80) and was compared to a matched non-symptomatic control group (n=80). The relationship between brain activity during successful and unsuccessful inhibitions and gray matter volume were compared with the ICV. A mediation analysis was conducted to examine if specific brain regions mediated the relationship between ADHD symptoms and ICV. Lastly, we looked at functional connectivity across various brain networks and quantified both positive and negative correlations during “Go” responses on the Stop Signal Task. Results: The brain data revealed that higher ICV was associated with increased structural and functional brain activation in the precentral gyrus in the whole sample and in adolescents with ADHD symptoms. Lower ICV was associated with lower activation in the anterior cingulate cortex (ACC) and medial frontal gyrus in the whole sample and in the control group. Furthermore, our results indicated that activation in the precentral gyrus (Broadman Area 4) mediated the relationship between ADHD symptoms and behavioural ICV. Conclusion: This is the first study first to investigate the functional and structural correlates of ICV collectively in a large adolescent sample. Our findings demonstrate a concurrent increase in brain structure and function within task-active prefrontal networks as a function of increased RT variability. Furthermore, structural and functional brain activation patterns in the ACC, and medial frontal gyrus plays a role-optimizing top-down control in order to maintain task performance. Our results also evidenced clear differences in brain morphometry between adolescents with symptoms of ADHD but without clinical diagnosis and typically developing controls. Our findings shed light on specific functional and structural brain regions that are implicated in ICV and yield insights into effective cognitive control in healthy individuals and in clinical groups.

Keywords: ADHD, fMRI, reaction-time variability, default mode, functional connectivity

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