Search results for: neuronal plasticity

Authors: Mohammad Zaid, Md. Rehan Sadique

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Underground structures are an integral part of urban infrastructures. Tunnels are being used for the transportation of humans and goods from distance to distance. Terrorist attacks on underground structures such as tunnels have resulted in the improvement of design methodologies of tunnels. The design of underground tunnels must include anti-terror design parameters. The study has been carried out to analyse the rock tunnel when subjected to internal blast loading. The finite element analysis has been carried out for 30m by 30m of the cross-section of the tunnel and 35m length of extrusion of the rock tunnel model. The effect of tunnel diameter and overburden depth of tunnel has been studied under internal blast loading. Four different diameters of tunnel considered are 5m, 6m, 7m, and 8m, and four different overburden depth of tunnel considered are 5m, 7.5m, 10m, and 12.5m. The mohr-coulomb constitutive material model has been considered for the Quartzite rock. A concrete damage plasticity model has been adopted for concrete tunnel lining. For the trinitrotoluene (TNT) Jones-Wilkens-Lee (JWL) material model has been considered. Coupled-Eulerian-Lagrangian (CEL) approach for blast analysis has been considered in the present study. The present study concludes that a shallow tunnel having smaller diameter needs more attention in comparison to blast resistant design of deep tunnel having a larger diameter. Further, in the case of shallow tunnels, more bulging has been observed, and a more substantial zone of rock has been affected by internal blast loading.

Keywords: finite element method, blast, rock, tunnel, CEL, JWL

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Authors: Alexandre H. Okano, Pedro M. D. Agrícola, Daniel G. Da S. Machado, Luiz I. Do N. Neto, Luiz F. Farias Junior, Paulo H. D. Nascimento, Rickson C. Mesquita, John F. Araujo, Eduardo B. Fontes, Hassan M. Elsangedy, Shinsuke Shimojo, Li M. Li

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The prefrontal cortex is involved in the reward system and the insular cortex integrates the afferent inputs arriving from the body’ systems and turns into feelings. Therefore, modulating neuronal activity in these regions may change individuals’ perception in a given situation such as exercise. We tested whether transcranial direct current stimulation (tDCS) change cerebral oxygenation and pleasure during exercise. Fourteen volunteer healthy adult men were assessed into five different sessions. First, subjects underwent to a maximum incremental test on a cycle ergometer. Then, subjects were randomly assigned to a transcranial direct current stimulation (2mA for 15 min) intervention in a cross over design in four different conditions: anode and cathode electrodes on T3 and Fp2 targeting the insular cortex, and Fpz and F4 targeting prefrontal cortex, respectively; and their respective sham. These sessions were followed by 30 min of moderate intensity exercise. Brain oxygenation was measured in prefrontal cortex with a near infrared spectroscopy. Perceived exertion and pleasure were also measured during exercise. The asymmetry in prefrontal cortex oxygenation before the stimulation decreased only when it was applied over this region which did not occur after insular cortex or sham stimulation. Furthermore, pleasure was maintained during exercise only after prefrontal cortex stimulation (P > 0.7), while there was a decrease throughout exercise (P < 0.03) during the other conditions. We conclude that tDCS over the prefrontal cortex changes brain oxygenation in ventromedial prefrontal cortex and maintains perceived pleasure during exercise. Therefore, this technique might be used to enhance effective responses related to exercise.

Keywords: affect, brain stimulation, dopamine neuromodulation, pleasure, reward, transcranial direct current stimulation

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Authors: Fatima Ghassan Al-Abtah, Naser Al-Huniti, Elsadig Mahdi

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As the lightest constructional metal on earth, magnesium alloys offer excellent potential for weight reduction in the transportation industry, and it was observed that some magnesium alloys exhibit superior ductility and superplastic behavior at high temperatures. The main limitation of the superplastic forming (SPF) includes the low production rate since it needs a long forming time for each part. Through this study, an SPF process that starts with a mechanical pre-forming stage is developed to promote formability and reduce forming time. A two-dimensional finite element model is used to simulate the process. The forming process consists of two steps. At the pre-forming step (deep drawing), the sheet is drawn into the die to a preselected level, using a mechanical punch, and at the second step (SPF) a pressurized gas is applied at a controlled rate. It is shown that a significant reduction in forming time and improved final thickness uniformity can be achieved when the hybrid forming technique is used, where the process achieved a fully formed part at 400°C. Investigation for the impact of different forming process parameters achieved by comparing forming time and the distribution of final thickness that were obtained from the simulation analysis. Maximum thinning decreased from over 67% to less than 55% and forming time significantly decreased by more than 6 minutes, and the required gas pressure profile was predicted for optimum forming process parameters based on the 0.001/sec target constant strain rate within the sheet.

Keywords: magnesium, plasticity, superplastic forming, finite element analysis

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Authors: Filip Franciszek Karuga, Szymon Turkiewicz, Marta Ditmer, Marcin Sochal, Piotr Białasiewicz, Agata Gabryelska

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Circadian rhythm, an internal coordinator of physiological processes is composed of a set of semi-autonomous clocks. Clocks are regulated through the expression of circadian clock genes which form feedback loops, creating an oscillator. The primary loop consists of activators: CLOCK, BMAL1 and repressors: CRY, PER. CLOCK can be substituted by the Neuronal PAS Domain Protein 2 (NPAS2). Orphan nuclear receptor (REV-ERB-α) is a component of the secondary major loop, modulating the expression of BMAL1. Circadian clocks might be disrupted by the obstructive sleep apnea (OSA), which has also been associated with type II diabetes mellitus (DM2). Interestingly, studies suggest that dysregulation of NPAS2 and REV-ERB-α might contribute to the pathophysiology of DM2 as well. The goal of our study was to examine the role of NPAS2 and REV-ERB-α in DM2 in OSA patients. After examination of the clinical data, all participants underwent polysomnography (PSG) to assess their apnea-hypopnea index (AHI). Based on the acquired data participants were assigned to one of 3 groups: OSA (AHI>30, no DM2; n=17 for NPAS2 and 34 for REV-ERB-α), DM2 (AHI>30 + DM2; n=7 for NPAS2 and 15 for REV-ERB-α) and control group (AHI<5, no DM2; n=16 for NPAS2 and 31 for REV-ERB-α). ELISA immunoassay was performed to assess the serum protein level of REV-ERB-α and NPAS2. The only statistically significant difference between groups was observed in NPAS2 protein level (p=0.037). Post-hoc analysis showed significant differences between the OSA and the control group (p=0.017). AHI and NPAS2 level was significantly correlated (r=-0.478, p=0.002) in all groups. A significant correlation was observed between the REV-ERB-α level and sleep efficiency (r=0.617, p=0.005) as well as sleep maintenance efficiency (r=0.645, p=0.003) in the OSA group. We conclude, that NPAS2 is associated with OSA severity and might contribute to metabolic sequelae of this disease. REV-ERB-α on the other hand can influence sleep continuity and efficiency.

Keywords: OSA, diabetes mellitus, endocrinology, chronobiology

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Authors: Wei-Chia Huang, Jane Wang

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Damage to nerves is considered one of the most irreversible injuries. The regeneration of nerves has always been an important topic in regenerative medicine. In general, damage to human tissue will naturally repair overtime. However, when the nerves are damaged, healed flesh wound cannot guarantee full restoration to its original function, as truncated nerves are often irreversible. Therefore, the development of treatment methods to successfully guide and accelerate the regeneration of nerves has been highly sought after. In order to induce nerve tissue growth, nerve conduits are commonly used to help reconnect broken nerve bundles to provide protection to the location of the fracture while guiding the growth of the nerve bundles. To prevent the protected tissue from becoming necrotic and to ensure the growth rate, the conduits used are often modified with microstructures or blended with neuron growth factors that may facilitate nerve regeneration. Electrical stimulation is another attempted treatment for medical rehabilitation. With appropriate range of voltages and stimulation frequencies, it has been demonstrated to promote cell proliferation and migration. Biodegradability are critical for medical devices like nerve conduits, while conductive polymers pose great potential toward the differentiation and growth of nerve cells. In this work, biodegradability and conductivity were combined into a novel biodegradable, photocurable, conductive polymer composite materials by embedding conductive nanoparticles in poly(glycerol sebacate) acrylate (PGSA) and 3D-printed into nerve conduits. Rat pheochromocytoma cells and rat neuronal Schwann cells were chosen for the in vitro tests of the conduits and had demonstrate selective growth upon culture in the conductive conduits with built-in microchannels and electrical stimulation.

Keywords: biodegradable polymer, 3d printing, neural regeneration, electrical stimulation

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Authors: M. M. Alhaji, M. Alhassan, A. M. Yahaya

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Soil engineers pay very little or no attention to variation in the mineralogical and consequently, the geotechnical properties of overburden with depth on basement complexes, a situation which can lead to sudden failure of civil engineering structures. Soil samples collected at depths ranging from 0.5m to 4.0m at 0.5m intervals, from a trial pit dogged manually to depth of 4.0m on an overburden over gneiss basement complex, was evaluated for physico-chemical, mineralogical and physical properties. This is to determine the variation of these properties with depth within the profile of the strata. Results showed that sodium amphibolite and feldspar, which are both primary minerals dominate the overall profile of the overburden. Carbon which dominates the lower profile of the strata was observed to alter to gregorite at upper section of the profile. Organic matter contents and cation exchange capacity reduces with increase in depth while lost on ignition and pH were relatively constant with depth. The index properties, as well as natural moisture contents, increases from 0.5m to between 1.0m to 1.5m depth after which the values reduced to constant values at 3.0m depth. The grain size analysis shows high composition of sand sized particles with silts of low to non-plasticity. The maximum dry density (MDD) values are generally relatively high and increases from 2.262g/cm³ at 0.5m depth to 2.410g/cm³ at 4.0m depth while the optimum moisture content (OMC) reduced from 9.8% at 0.5m depth to 6.7% at 4.0m depth.

Keywords: Gneiss basement complex, mineralogical properties, North Central Nigeria, physico-chemical properties, physical properties, overburden soil

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Authors: Hamzeh Alipour, Masoumeh Bagheri, Tahereh Karamzadeh, Abbasali Raz, Kourosh Azizi

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Netrin-A, a protein identified for conducting commissural axons, has a similar role in angiogenesis. In addition, studies have shown that one of the netrin-A receptors is expressed in the growing cells of small capillaries. It will be interesting to study this new group of molecules because their role in wound healing will become clearer in the future due to angiogenesis. The greenbottle blowfly Luciliasericata (L. sericata) larvae are increasingly used in maggot therapy of chronic wounds. This aim of this was the identification of moleculareatures of Netrin-A in L. sericata larvae. Larvae were reared under standard maggotarium conditions. The nucleic acid sequence of L. sericataNetrin-A (LSN-A) was then identified using Rapid Amplification of cDNA Ends (RACE) and Rapid Amplification of Genomic Ends (RAGE). Parts of the Netrin-A gene, including the middle, 3′-, and 5′-ends were identified, TA cloned in pTG19 plasmid, and transferred into DH5ɑ Escherichia coli. Each part was sequenced and assembled using SeqMan software. This gene structure was further subjected to in silico analysis. The DNA of LSN-A was identified to be 2407 bp, while its mRNA sequence was recognized as 2115 bp by Oligo0.7 software. It translated the Netrin-A protein with 704 amino acid residues. Its molecular weight is estimated to be 78.6 kDa. The 3-D structure ofNetrin-A drawn by SWISS-MODEL revealed its similarity to the Netrin-1 of humans with 66.8% identity. The LSN-A protein conduces to repair the myelin membrane in neuronal cells. Ultimately, it can be an effective candidate in neural regeneration and wound healing. Furthermore, our next attempt is to deplore recombinant proteins for use in medical sciences.

Keywords: maggot therapy, netrin-A, RACE, RAGE, lucilia sericata

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Authors: Hanen Bouaziz, Françoise Croute, Najiba Zeghal

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In order to investigate the toxic effects of fluoride on cerebrum maturity of suckling mice, we treated adult female mice of Swiss Albinos strain by 500 ppm NaF in their drinking water from the 15th day of pregnancy until the day 14 after delivery. All mice were sacrificed on day 14 after parturition. During treatment, levels of thiobarbituric acid reactive substances, the marker of lipid peroxidation extend, increased, while the activities of the antioxidant enzymes such as glutathione peroxidase, superoxide dismutase and catalase and the level of glutathione decreased significantly in cerebellum compared with those of the control group. These results suggested that fluoride enhanced oxidative stress, thereby disturbing the antioxidant defense of nursing pups. In addition, acetylcholinesterase activity in cerebellum was inhibited after treatment with fluoride. In cerebellum of mice, migration of neurons from the external granular layer to the internal granular layer occurred postnatally. Key guidance signals to these migrating neurons were provided by laminin, an extracellular matrix protein fixed to the surface of astrocytes. In the present study, we examined the expression and distribution of laminin in cerebellum of 14-day-old mice. Immunoreactive laminin was disappeared by postnatal day 14 in cerebellum parenchyma of control pups and was restricted to vasculature despite the continued presence of granular cells in the external granular layer. In contrast, in cerebellum of NaF treated pups, laminin was deposited in organised punctuate clusters in the molecular layer. These data indicated that the disruption of laminin distribution might play a major role in the profound derangement of neuronal migration observed in cerebellum of NaF treated pups.

Keywords: acetylcholinesterase activity, cerebellum, laminin, oxidative stress, suckling mice

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Authors: Ivandic Kreso, Spiranec Miljenko, Kavur Boris, Strelec Stjepan

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This article discusses the possibility of using dilatometer tests (DMT) together with in situ seismic tests (MASW) in order to get the shape of G-g degradation curve in cohesive soils (clay, silty clay, silt, clayey silt and sandy silt). MASW test provides the small soil stiffness (G_o from v_s) at very small strains and DMT provides the stiffness of the soil at ‘work strains’ (M_DMT). At different test locations, dilatometer shear stiffness of the soil has been determined by the theory of elasticity. Dilatometer shear stiffness has been compared with the theoretical G-g degradation curve in order to determine the typical range of shear deformation for different types of cohesive soil. The analysis also includes factors that influence the shape of the degradation curve (G-g) and dilatometer modulus (M_DMT), such as the overconsolidation ratio (OCR), plasticity index (IP) and the vertical effective stress in the soil (s_vo'). Parametric study in this article defines the range of shear strain g_DMT and G_DMT/G_o relation depending on the classification of a cohesive soil (clay, silty clay, clayey silt, silt and sandy silt), function of density (loose, medium dense and dense) and the stiffness of the soil (soft, medium hard and hard). The article illustrates the potential of using MASW and DMT to obtain G-g degradation curve in cohesive soils.

Keywords: dilatometer testing, MASW testing, shear wave, soil stiffness, stiffness reduction, shear strain

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Authors: Jatupon Em-Udom, Nirand Pisutha-Arnond

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The phase-field-crystal, PFC, approach is a density-functional-type material model with an atomic resolution on a diffusive timescale. Spatially, the model incorporates periodic nature of crystal lattices and can naturally exhibit elasticity, plasticity and crystal defects such as grain boundaries and dislocations. Temporally, the model operates on a diffusive timescale which bypasses the need to resolve prohibitively small atomic-vibration time steps. The PFC model has been used to study many material phenomena such as grain growth, elastic and plastic deformations and solid-solid phase transformations. In this study, the pressure-controlled dynamic equation for the PFC model was developed to simulate a single-component system under externally applied pressure; these coupled equations are important for studies of deformable systems such as those under constant pressure. The formulation is based on the non-equilibrium thermodynamics and the thermodynamics of crystalline solids. To obtain the equations, the entropy variation around the equilibrium point was derived. Then the resulting driving forces and flux around the equilibrium were obtained and rewritten as conventional thermodynamic quantities. These dynamics equations are different from the recently-proposed equations; the equations in this study should provide more rigorous descriptions of the system dynamics under externally applied pressure.

Keywords: driving forces and flux, evolution equation, non equilibrium thermodynamics, Onsager’s reciprocal relation, phase field crystal model, thermodynamics of single-component solid

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Authors: Kyungae Jo, Eun Young Kim, Byungsoo Shin, Kwang Soon Shin, Hyung Joo Suh

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Gamma-aminobutyric acid (GABA) and 5-hydroxytryptophan (5-HTP) are amino acids of digested nutrients or food ingredients and these can possibly be utilized as non-pharmacologic treatment for sleep disorder. We previously investigated the GABA/5-HTP mixture is the principal concept of sleep-promoting and activity-repressing management in nervous system of D. melanogaster. Two experiments in this study were designed to evaluate sleep-promoting effect of GABA/5-HTP mixture, to clarify the possible ratio of sleep-promoting action in the Drosophila invertebrate model system. Behavioral assays were applied to investigate distance traveled, velocity, movement, mobility, turn angle, angular velocity and meander of two amino acids and GABA/5-HTP mixture with caffeine treated flies. In addition, differentially expressed gene (DEG) analyses from next generation sequencing (NGS) were applied to investigate the signaling pathway and functional interaction network of GABA/5-HTP mixture administration. GABA/5-HTP mixture resulted in significant differences between groups related to behavior (p < 0.01) and significantly induced locomotor activity in the awake model (p < 0.05). As a result of the sequencing, the molecular function of various genes has relationship with motor activity and biological regulation. These results showed that GABA/5-HTP mixture administration significantly involved the inhibition of motor behavior. In this regard, we successfully demonstrated that using a GABA/5-HTP mixture modulates locomotor activity to a greater extent than single administration of each amino acid, and that this modulation occurs via the neuronal system, neurotransmitter release cycle and transmission across chemical synapses.

Keywords: sleep, γ-aminobutyric acid, 5-hydroxytryptophan, Drosophila melanogaster

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Authors: Yong Jae Yu, Jae-Yeol Cho

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In the design of structural concrete for impact loading, design or model codes often employ a dynamic increase factor (DIF) to impose dynamic effect on static response. Dynamic increase factors that are obtained from laboratory material test results and that are commonly given as a function of strain rate only are quite different from each other depending on the design concept of design codes like ACI 349M-06, fib Model Code 2010 and ACI 370R-14. Because the dynamic increase factors currently adopted in the codes are too simple and limited to consider a variety of strength of materials, their application in practical design is questionable. In this study, the dynamic increase factors used in the three codes were validated through the finite element analysis of reinforced concrete slab elements which were tested and reported by other researcher. The test was intended to simulate a wall element of the containment building in nuclear power plants that is assumed to be subject to impact scenario that the Pentagon experienced on September 11, 2001. The finite element analysis was performed using the ABAQAUS 6.10 and the plasticity models were employed for the concrete, reinforcement. The dynamic increase factors given in the three codes were applied to the stress-strain curves of the materials. To estimate the dynamic increase factors, strain rate was adopted as a parameter. Comparison of the test and analysis was done with regard to perforation depth, maximum deflection, and surface crack area of the slab. Consequently, it was found that DIF has so great an effect on the behavior of the reinforced concrete structures that selection of DIF should be very careful. The result implies that DIF should be provided in design codes in more delicate format considering various influence factors.

Keywords: impact, strain rate, DIF, slab elements

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Authors: Shuangxin Wu

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Superalloy ultra-thin-walled components occupy a considerable proportion of aero engines and play an increasingly important role in structural weight reduction and performance improvement. To solve problems such as high deformation resistance and poor formability at room temperature, the introduction of pulse current in the processing process can improve the plasticity of metal materials, but the influence mechanism of pulse current on the forming limit of superalloy ultra-thin sheet is not clear, which is of great significance for determining the material processing window and improving the micro-forming process. The effect of pulse current on the microstructure evolution of superalloy thin plates was observed by optical microscopy (OM) and X-ray diffraction topography (XRT) by applying pulse current to GH3039 with a thickness of 0.2mm under plane strain and uniaxial tensile states. Compared with the specimen without pulse current applied at the same temperature, the internal void volume fraction is significantly reduced, reflecting the non-thermal effect of pulse current on the growth of micro-pores. ED (electrically deforming) specimens have larger and deeper dimples, but the elongation is not significantly improved because the pulse current promotes the void coalescence process, resulting in material fracture. The electro-plastic phenomenon is more obvious in the plane strain state, which is closely related to the effect of stress triaxial degree on the void evolution under pulsed current.

Keywords: pulse current, superalloy, ductile fracture, void damage

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Authors: Amir Zeb, Shailima Rampogu, Minky Son, Ayoung Baek, Sang H. Yoon, Keun W. Lee

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Neurotoxic insults activate calpain, which in turn produces truncated p25 from p35. p25 forms hyperactivated Cdk5/p25 complex, and thereby induces severe neuropathological aberrations including hyperphosphorylated tau, neuroinflammation, apoptosis, and neuronal death. Inhibition of Cdk5/p25 complex alleviates aberrant phosphorylation of tau to mitigate AD pathology. PHA-793887 and Roscovitine have been investigated as selective inhibitors of Cdk5/p25 with IC50 values 5nM and 160nM, respectively, but their mechanistic studies remain unknown. Herein, computational simulations have explored the binding mode and interaction mechanism of PHA-793887 and Roscovitine with Cdk5/p25. Docking results suggested that PHA-793887 and Rsocovitine have occupied the ATP-binding site of Cdk5 and obtained highest docking (GOLD) score of 66.54 and 84.03, respectively. Furthermore, molecular dynamics (MD) simulation demonstrated that PHA-793887 and Roscovitine established stable RMSD of 1.09 Å and 1.48 Å with Cdk5/p25, respectively. Profiling of polar interactions suggested that each inhibitor formed hydrogen bonds (H-bond) with catalytic residues of Cdk5 and could remain stable throughout the molecular dynamics simulation. Additionally, binding free energy calculation by molecular mechanics/Poisson–Boltzmann surface area (MM/PBSA) suggested that PHA-793887 and Roscovitine had lowest binding free energies of -150.05 kJ/mol and -113.14 kJ/mol, respectively with Cdk5/p25. Free energy decomposition demonstrated that polar energy by H-bond between the Glu81 of Cdk5 and PHA-793887 is the essential factor to make PHA-793887 highly selective towards Cdk5/p25. Overall, this study provided substantial evidences to explore mechanistic interactions of the selective inhibitors of Cdk5/p25 and could be used as fundamental considerations in the development of structure-based selective inhibitors of Cdk5/p25.

Keywords: Cdk5/p25 inhibition, molecular modeling of Cdk5/p25, PHA-793887 and roscovitine, selective inhibition of Cdk5/p25

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Authors: D. Jayalakshmi, S. S. Bhosale

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This paper, in its first part, presents the state-of-the-art literature of design approaches for geosynthetic reinforced unpaved roads. The literature starting since 1970 and the critical appraisal of flexible pavement design by Giroud and Han (2004) and Jonathan Fannin (2006) is presented. The design example is illustrated for Indian conditions. The example emphasizes the results computed by Giroud and Han's (2004) design method with the Indian road congress guidelines by IRC SP 72 -2015. The input data considered are related to the subgrade soil condition of Maharashtra State in India. The unified soil classification of the subgrade soil is inorganic clay with high plasticity (CH), which is expansive with a California bearing ratio (CBR) of 2% to 3%. The example exhibits the unreinforced case and geotextile as reinforcement by varying the rut depth from 25 mm to 100 mm. The present result reveals the base thickness for the unreinforced case from the IRC design catalogs is in good agreement with Giroud and Han (2004) approach for a range of 75 mm to 100 mm rut depth. Since Giroud and Han (2004) method is applicable for both reinforced and unreinforced cases, for the same data with appropriate Nc factor, for the same rut depth, the base thickness for the reinforced case has arrived for the Indian condition. From this trial, for the CBR of 2%, the base thickness reduction due to geotextile inclusion is 35%. For the CBR range of 2% to 5% with different stiffness in geosynthetics, the reduction in base course thickness will be evaluated, and the validation will be executed by the full-scale accelerated pavement testing set up at the College of Engineering Pune (COE), India.

Keywords: base thickness, design approach, equation, full scale accelerated pavement set up, Indian condition

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Authors: David Polcari, Samuel C. Perry, Loredano Pollegioni, Matthias Geissler, Janine Mauzeroll

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ᴅ-serine acts as an endogenous co-agonist for N-methyl-ᴅ-aspartate receptors in neuronal synapses. This makes it a key component in the development and function of a healthy brain, especially given its role in several neurodegenerative diseases such as Alzheimer’s disease and dementia. Despite such clear research motivations, the primary site and mechanism of ᴅ-serine release is still currently unclear. For this reason, we are developing a biosensor for the detection of ᴅ-serine utilizing a microelectrode in combination with a ᴅ-amino acid oxidase enzyme, which produces stoichiometric quantities of hydrogen peroxide in response to ᴅ-serine. For the fabrication of a biosensor with good selectivity, we use a permselective poly(meta-phenylenediamine) film to ensure only the target molecule is reacted, according to the size exclusion principle. In this work, we investigated the effect of the electrodeposition conditions used on the biosensor’s response time and selectivity. Careful optimization of the fabrication process allowed for enhanced biosensor response time. This allowed for the real time sensing of ᴅ-serine in a bulk solution, and also provided in means to map the efflux of ᴅ-serine in real time. This was done using scanning electrochemical microscopy (SECM) with the optimized biosensor to measure localized release of ᴅ-serine from an agar filled glass capillary sealed in an epoxy puck, which acted as a model system. The SECM area scan simultaneously provided information regarding the rate of ᴅ-serine flux from the model substrate, as well as the size of the substrate itself. This SECM methodology, which provides high spatial and temporal resolution, could be useful to investigate the primary site and mechanism of ᴅ-serine release in other biological samples.

Keywords: ᴅ-serine, enzymatic biosensor, microelectrode, scanning electrochemical microscopy

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Authors: Ali Golestani, Vahid Naseri, Hossein Taheri

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Recently, some of studies examined the effect of exercise on neurotrophic factors influencing the growth, protection, plasticity and function in central and peripheral nerve cells. The aim of this study was to investigate the effects of continuous and interval aerobic exercises with moderate intensity on serum levels of glial cell line-derived neurotrophic factor (GDNF) and aerobic capacity in obese children. 21 obese students with an average age of 13.6 ± 0.5 height 171 ± 5 and BMI 32 ± 1.2 were divided randomly to control, continuous aerobic and interval aerobic groups. Training protocol included continuous or interval aerobic exercises with moderate intensity 50-65%MHR, three times per week for 10 weeks. 48 hours before and after executing of protocol, blood samples were taken from the participants and their GDNF serum levels were measured by ELISA. Aerobic power was estimated using Shuttle-run test. T-test results indicated a small increase in their GDNF serum levels, which was not statistically significant (p =0.11). In addition, the results of ANOVA did not show any significant difference between continuous and interval aerobic training on the serum levels of their GDNF but their aerobic capacity significantly increased (p =0.012). Although continuous and interval aerobic exercise improves aerobic power in obese children, they had no significant effect on their serum levels of GDNF.

Keywords: aerobic power, continuous aerobic training, glial cell line-derived neurotrophic factor (GDNF), interval aerobic training, obese children

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Authors: T. N. Girish, B. E. Pradeep, Ravi Parkash

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Insects from tropical wet or dry seasons are likely to cope starvation stress through seasonal phenotypic plasticity in energy metabolites. Accordingly, we analyzed such plastic changes in Zaprionus indianus flies reared under wet or dry season-specific conditions; and also after adult acclimation at 32℃ for 1 to 6 days; and to low (40% RH) or high (70% RH) humidity. Both thermal or humidity acclimation revealed significant accumulation of body lipids for wet season flies but low humidity acclimation did not change the level of body lipids in dry season flies. Developmental and adult acclimation showed sex specific differences i.e., starvation resistance and body lipids were higher in the males of dry season but in females of wet season. We found seasonal and sex specific differences in the relative level for body lipids at death; and in the rates of accumulation or utilization of energy metabolites (body lipids, carbohydrates and proteins). Body lipids constitute the preferred energy source under starvation for flies of both the seasons. However, utilization of carbohydrates (~20% to 30%) and proteins (~20% to 25%) was evident only in dry season flies. Higher starvation resistance after thermal or humidity acclimation is achieved by increased accumulation of lipids. Adult acclimation of wet or dry season flies revealed plastic changes in mean daily fecundity despite reduction in fecundity under starvation. Thus, thermal or humidity induced plastic responses in body lipids support starvation resistance under wet or dry seasons.

Keywords: heat or humidity acclimation, plastic changes in body lipids and starvation resistance, tropical drosophilid, Wet- or Dry seasons, Zaprionus indianus

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Authors: João Paulo Pascon

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In this work, a mixed 3D finite element formulation is proposed in order to analyze thermoviscoplastic materials under large strain levels and ductile damage. To this end, a tetrahedral element of linear order is employed, considering a thermoviscoplastic constitutive law together with the neo-Hookean hyperelastic relationship and a nonlocal Gurson`s porous plasticity theory The material model is capable of reproducing finite deformations, elastoplastic behavior, void growth, nucleation and coalescence, thermal effects such as plastic work heating and conductivity, strain hardening and strain-rate dependence. The nonlocal character is introduced by means of a nonlocal parameter applied to the Laplacian of the porosity field. The element degrees of freedom are the nodal values of the deformed position, the temperature and the nonlocal porosity field. The internal variables are updated at the Gauss points according to the yield criterion and the evolution laws, including the yield stress of matrix, the equivalent plastic strain, the local porosity and the plastic components of the Cauchy-Green stretch tensor. Two problems involving 3D specimens and ductile damage are numerically analyzed with the developed computational code: the necking problem and a notched sample. The effect of the nonlocal parameter and the mesh refinement is investigated in detail. Results indicate the need of a proper nonlocal parameter. In addition, the numerical formulation can predict ductile fracture, based on the evolution of the fully damaged zone.

Keywords: mixed finite element, large strains, ductile damage, thermoviscoplasticity

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Authors: K. S. Zaytsev, Y. R. Nartsissov

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Glycine is one of the key inhibitory neurotransmitters in Central nervous system (CNS) meanwhile glycinergic transmission is highly dependable on its appropriate reuptake from synaptic cleft. Glycine transporters (GlyT) of types 1 and 2 are the enzymes providing glycine transport back to neuronal and glial cells along with Na⁺ and Cl⁻ co-transport. The distribution and stoichiometry of GlyT1 and GlyT2 differ in details, and GlyT2 is more interesting for the research as it reuptakes glycine to neuron cells, whereas GlyT1 is located in glial cells. In the process of GlyT2 activity, the translocation of the amino acid is accompanied with binding of both one chloride and three sodium ions consequently (two sodium ions for GlyT1). In the present study, we developed a computer simulator of GlyT2 and GlyT1 activity based on known experimental data for quantitative estimation of membrane glycine transport. The trait of a single protein functioning was described using the probability approach where each enzyme state was considered separately. Created scheme of transporter functioning realized as a consequence of elemental steps allowed to take into account each event of substrate association and dissociation. Computer experiments using up-to-date kinetic parameters allowed receiving the number of translocated glycine molecules, Na⁺ and Cl⁻ ions per time period. Flexibility of developed software makes it possible to evaluate glycine reuptake pattern in time under different internal characteristics of enzyme conformational transitions. We investigated the behavior of the system in a wide range of equilibrium constant (from 0.2 to 100), which is not determined experimentally. The significant influence of equilibrium constant in the range from 0.2 to 10 on the glycine transfer process is shown. The environmental conditions such as ion and glycine concentrations are decisive if the values of the constant are outside the specified range.

Keywords: glycine, inhibitory neurotransmitters, probability approach, single protein functioning

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Authors: I. Wardana Ketut, I. Suparwa Nyoman

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This study investigated the form and characteristic of speech sound produced by three Balinese subjects who have recovered from aphasia as well as intervened their language impairment on side of linguistic and neuronal aspects of views. The failure of judging the speech sound was caused by impairment of motor cortex that indicated there were lesions in left hemispheric language zone. Sound articulation phenomena were in the forms of phonemes deletion, replacement or assimilation in individual words and meaning building for anomic aphasia. Therefore, the Balinese sound patterns were stimulated by showing pictures to the subjects and recorded to recognize what individual consonants or vowels they unclearly produced and to find out how the sound disorder occurred. The physiology of sound production by subject’s speech organs could not only show the accuracy of articulation but also any level of severity the lesion they suffered from. The subjects’ speech sounds were investigated, classified and analyzed to know how poor the lingual units were and observed to clarify weaknesses of sound characters occurred either for place or manner of articulation. Many fricative and stopped consonants were replaced by glottal or palatal sounds because the cranial nerve, such as facial, trigeminal, and hypoglossal underwent impairment after the stroke. The phonological intervention was applied through a technique called phonemic articulation drill and the examination was conducted to know any change has been obtained. The finding informed that some weak articulation turned into clearer sound and simple meaning of language has been conveyed. The hierarchy of functional parts of brain played important role of language formulation and processing. From this finding, it can be clearly emphasized that this study supports the role of right hemisphere in recovery from aphasia is associated with functional brain reorganization.

Keywords: aphasia, intervention, phonology, stroke

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Authors: Veronika Lesáková, Silvia Slezáková, František Štěpánek

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Drug dosage forms consisting of multi-unit particle systems (MUPS) for modified drug release provide a promising route for overcoming the limitation of conventional tablets. Despite the conventional use of pellets as units for MUP systems, 3D printed polymers loaded with a drug seem like an interesting candidate due to the control over dosing that 3D printing mechanisms offer. Further, 3D printing offers high flexibility and control over the spatial structuring of a printed object. The final MUPS tablets include PVP and HPC as granulate with other excipients, enabling the compaction process of this mixture with 3D printed inclusions, also termed minitablets. In this study, we have developed the multi-step production process for MUPS tablets, including the 3D printing technology. The MUPS tablets with incorporated 3D printed minitablets are a complex system for drug delivery, providing modified drug release. Such structured tablets promise to reduce drug fluctuations in blood, risk of local toxicity, and increase bioavailability, resulting in an improved therapeutic effect due to the fast transfer into the small intestine, where particles are evenly distributed. Drug loaded 3D printed minitablets were compacted into the excipient mixture, influencing drug release through varying parameters, such as minitablets size, matrix composition, and compaction parameters. Further, the mechanical properties and morphology of the final MUPS tablets were analyzed as many properties, such as plasticity and elasticity, can significantly influence the dissolution profile of the drug.

Keywords: 3D printing, dissolution kinetics, drug delivery, hot-melt extrusion

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Authors: Nandini Nalika, Suhel Parvez

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Nanotechnology has emerged to play a vital role in developing all through the industrial world with an immense production of nanomaterials including nanoparticles (NPs). Many toxicological studies have confirmed that due to unique small size and physico-chemical properties of NPs (1-100nm), they can be potentially hazardous. Metallic NPs of small size have been shown to induce higher levels of cellular oxidative stress and can easily pass through the Blood Brain Barrier (BBB) and significantly accumulate in brain. With the wide applications of titanium dioxide nanoparticles (TNPs) in day-to-day life in form of cosmetics, paints, sterilisation and so on, there is growing concern regarding the deleterious effects of TNPs on central nervous system and mitochondria appear to be important cellular organelles targeted to the pro-oxidative effects of NPs and an important source that contribute significantly for the production of reactive oxygen species after some toxicity or an injury. The aim of our study was to elucidate the effect of TNPs in anatase form with different concentrations (5-50 µg/ml) following with various oxidative stress markers in isolated brain mitochondria as an in vitro model. Oxidative stress was determined by measuring the different oxidative stress markers like lipid peroxidation as well as the protein carbonyl content which was found to be significantly increased. Reduced glutathione content and major glutathione metabolizing enzymes were also modulated signifying the role of glutathione redox cycle in the pathophysiology of TNPs. The study also includes the mitochondrial enzymes (Complex 1, Complex II, complex IV, Complex V ) and the enzymes showed toxicity in a relatively short time due to the effect of TNPs. The study provide a range of concentration that were toxic to the neuronal cells and data pointing to a general toxicity in brain mitochondria by TNPs, therefore, it is in need to consider the proper utilization of NPs in the environment.

Keywords: mitochondria, nanoparticles, brain, in vitro

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Authors: Mohmd Sarireh

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The geotechnical study can be employed successfully to assess and follow the expected development or delay in the project construction. The development project of city center or downtown was taken as a case study for the investigation of the project conditions that might support progress or cause delay. The project was proposed to build 7447 m2 by reinforced concrete mainly to serve and support the services provided to people in Tafila. The project construction had faced challenges and obstacles such as soil collapse because of excavation of the weak soil that found in the project site. In addition, the topography of the project area showed a high slope from South-West to North. The slope through the project footprint reached to 83.3% which is considered very high slope. One year and a half proposed to finish the project construction since the 1st of March 2013 and it was planned to be finished by the 31th of August 2014, but the project needs more than one year and a half as extension according to the consultant engineer. The collecting of data was conducted through the interviews with the engineers and officials, and by analyzing the soil reports and samples taken during design and excavation. The major findings came out to weak and fractured soil and construction waste that were found at project site. Also, soil was considered very fine according to the plasticity index (PI) values, in addition to the high depths required for foundation that contribute to the collapse of soil and the increase of project cost. The current project aims to present how the unseen conditions can delay the project construction and increase the cost of the project that rises to JD8.305 Million.

Keywords: geotechnical, management, progress, risk, soil unseen conditions management

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Authors: Yasam Palguna, Rajesh Korla

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The efficiency of thermally operated systems can be improved by increasing the operating temperature, thereby decreasing the fuel consumption and carbon footprint. Hence, there is a continuous need for replacing the existing materials with new alloys with higher temperature working capabilities. During the last decade, multi principal element alloys, commonly known as high entropy alloys are getting more attention because of their superior high temperature strength along with good high temperature corrosion and oxidation resistance, The present work focused on the microstructure and high temperature tensile behavior of Al0.2CoCrFeNiMo0.5 high entropy alloy (HEA). Wrought Al0.2CoCrFeNiMo0.5 high entropy alloy, produced by vacuum induction melting followed by thermomechanical processing, is tested in the temperature range of 200 to 900oC. It is exhibiting very good resistance to softening with increasing temperature up to 700oC, and thereafter there is a rapid decrease in the strength, especially beyond 800oC, which may be due to simultaneous occurrence of recrystallization and precipitate coarsening. Further, it is exhibiting superplastic kind of behavior with a uniform elongation of ~ 275 % at 900 oC temperature and 1 x 10-3 s-1 strain rate, which may be due to the presence of fine stable equi-axed grains. Strain rate sensitivity of 0.3 was observed, suggesting that solute drag dislocation glide might be the active mechanism during superplastic kind of deformation. Post deformation microstructure suggesting that cavitation at the sigma phase-matrix interface is the failure mechanism during high temperature deformation. Finally, high temperature properties of the present alloy will be compared with the contemporary high temperature materials such as ferritic, austenitic steels, and superalloys.

Keywords: high entropy alloy, high temperature deformation, super plasticity, post-deformation microstructures

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Authors: Zahra F. Al-Khateeb, Shenel Shekerzade, Hasna Boumenar, Siân M. Henson, Jordi L. Tremoleda, A. T. Michael-Titus

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Traumatic brain injury (TBI) is the leading cause of disability and death in young adults and also increases the risk ofneurodegeneration. The mechanisms linking moderate to severe TBI to neurodegeneration are not known. It has been proposed that cellular senescence inductionpost-injury could amplify neuroinflammation and induce long-term changes. The impact of these processes after injury to an immature brain has not been characterised yet. We carried out a controlled cortical impact injury (CCI) in juvenile 1 month-old male CD1 mice. Animals were anesthetised and received a unilateral CCI injury. The sham group received anaesthesia and had a craniotomy. A naïve group had no intervention. The brain tissue was analysed at 5 days and 35 days post-injury using immunohistochemistry and markers for microglia, astrocytes, and senescence. Compared tonaïve animals, injured mice showed an increased microglial and astrocytic reaction early post-injury, as reflected in Iba1 and GFAP markers, respectively; the GFAP increase persisted in the later phase. The senescence analysis showed a significant increase inγH2AX-53BP1 nuclear foci, 8-oxoguanine, p19ARF, p16INK4a, and p53 expression in naïve vs. sham groups and naïve vs. CCI groups, at 5 dpi. At 35 days, the difference was no longer statistically significant in all markers. The injury induced a decrease p21 expression vs. the naïve group, at 35 dpi. These results indicate the induction of a complex senescence response after immature brain injury. Some changes occur early and may reflect the activation/proliferation of non-neuronal cells post-injury that had been hindered, whereas changes such as p21 downregulation may reflect a delayed response and pro-repair processes.

Keywords: cellular senescence, traumatic brain injury, brain injury, controlled cortical impact

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Authors: Hyo-Min Kim, Seokjin Ham, Mi-Joung Yoo, Minseon Kim, Tae-Young Roh

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The gastrointestinal (GI) tract of most animals, including murine, is highly compartmentalized epithelia which also provide distinct different functions of its own tissue. Nevertheless, these epithelia share certain characteristics that enhance immune responses to infections and maintain the barrier function of the intestine. GI tract epithelia also undergo regeneration not only in homeostatic conditions but also in a response to the damage. A full turnover of the murine gastrointestinal epithelium occurs every 4-5 day, a process that is regulated and maintained by a minor population of Lgr5+ adult stem cell that commonly conserved in the bottom of crypts through GI tract. Maintenance of the stem cell is somehow regulated by epigenetic factors according to recent studies. Chromatin vacancy, remodelers, histone variants and histone modifiers could affect adult stem cell fate. In this study, Lgr5-EGFP reporter mouse was used to take advantage of exploring the epigenetic dynamics among Lgr5 positive mutual stem cell in GI tract. Cells were isolated by fluorescence-activated cell sorting (FACS), gene expression levels, chromatin accessibility changes and histone modifications were analyzed. Some notable chromatin structural related epigenetic variants were detected. To identify the overall cell-cell interaction inside the stem cell niche, an extensive genome-wide analysis should be also followed. According to the results, nevertheless, we expected a broader understanding of cellular niche maintaining stem cells and epigenetic barriers through conserved stem cell in GI tract. We expect that our study could provide more evidence of adult stem cell plasticity and more chances to understand each stem cell that takes parts in certain organs.

Keywords: adult stem cell, epigenetics, LGR5 stem cell, gastrointestinal tract

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Authors: Huimin Zhao, Xiaoquan Liu, Haochen Liu

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The major challenge facing Alzheimer's Disease (AD) drug development is how to effectively improve cognitive function in clinical practice. Growing evidence indicates that stimulating hippocampal neurogenesis is a strategy for restoring cognition in animal models of AD. The mitogen-activated protein kinase (MAPK) pathway is a crucial factor in neurogenesis, which is negatively regulated by Dual-specificity phosphatase 16 (DUSP16). Transcriptome analysis of post-mortem brain tissue revealed up-regulation of DUSP16 expression in AD patients. Additionally, DUSP16 was involved in regulating the proliferation and neural differentiation of neural progenitor cells (NPCs). Nevertheless, whether the effect of DUSP16 on ameliorating cognitive disorders by influencing NPCs differentiation in AD mice remains unclear. Our study demonstrates an association between DUSP16 SNPs and clinical progression in individuals with mild cognitive impairment (MCI). Besides, we found that increased DUSP16 expression in both 3×Tg and SAMP8 models of AD led to NPC differentiation impairments. By silencing DUSP16, cognitive benefits, the induction of AHN and synaptic plasticity, were observed in AD mice. Furthermore, we found that DUSP16 is involved in the process of NPC differentiation by regulating c-Jun N-terminal kinase (JNK) phosphorylation. Moreover, the increased DUSP16 may be regulated by the ETS transcription factor (ELK1), which binds to the promoter region of DUSP16. Loss of ELK1 resulted in decreased DUSP16 mRNA and protein levels. Our data uncover a potential regulatory role for DUSP16 in adult hippocampal neurogenesis and provide a possibility to find the target of AD intervention.

Keywords: alzheimer's disease, cognitive function, DUSP16, hippocampal neurogenesis

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Authors: Y. Wang, S. Zhang, X. Chen

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The longitudinal compressive strength of fibre reinforced plastic (FRP) possess a large stochastic variability, which limits efficient application of composite structures. This study aims to address how the random fibre packing affects the uncertainty of FRP compressive strength. An novel approach is proposed to generate random fibre packing status by a combination of Latin hypercube sampling and random sequential expansion. 3D nonlinear finite element model is built which incorporates both the matrix plasticity and fibre geometrical instability. The matrix is modeled by isotropic ideal elasto-plastic solid elements, and the fibres are modeled by linear-elastic rebar elements. Composite with a series of different nominal fibre volume fractions are studied. Premature fibre waviness at different magnitude and direction is introduced in the finite element model. Compressive tests on uni-directional CFRP (carbon fibre reinforced plastic) are conducted following the ASTM D6641. By a comparison of 3D FE models and compressive tests, it is clearly shown that the stochastic variation of compressive strength is partly caused by the random fibre packing, and normal or lognormal distribution tends to be a good fit the probabilistic compressive strength. Furthermore, it is also observed that different random fibre packing could trigger two different fibre micro-buckling modes while subjected to longitudinal compression: out-of-plane buckling and twisted buckling. The out-of-plane buckling mode results much larger compressive strength, and this is the major reason why the random fibre packing results a large uncertainty in the FRP compressive strength. This study would contribute to new approaches to the quality control of FRP considering higher compressive strength or lower uncertainty.

Keywords: compressive strength, FRP, micro-buckling, random fibre packing

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Authors: Liliana Rytel, Jarosław Całka

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One of the diseases that are very common health problem of modern man is the stomach hyperacidity. It is well known that this pathological state, during which gastric glands secrete too much of hydrochloric acid can be caused due to various factors such as stress, eating habits, alcohol, smoking and some, especially anti-inflammatory drugs. Moreover, hyperacidity is recognized as one of factors leading to development of peptic ulcer disease. Therefore, we analyzed expression of substance P (SP) and neuronal isoform of nitric oxide synthase (nNOS) in the porcine nodose ganglion sensory neurons innervating prepyloric stomach region in physiological state and following intragastric infusion of hydrochloric acid. The study was performed on 8 immature gilts of the Large White Polish breed. All animals were injected retrograde marker Fast Blue (FB) into the anterior prepyloric stomach wall. After injections of FB, pigs were divided into two groups: control (group C; n = 4) and experimental (HCL group, n = 4) and after convalescence period of 23 days, animals of HCL group were subjected to renewed anaesthesia. Then, 0.25 M aqueous solution of hydrochloric acid with a dose of 5 ml/kg body weight was administered intragastrically with use of a stomach tube. On 28th day, all control and HCL pigs were euthanized and bilateral reght (rNG) and left (lNG) were collected. Cryostat sections were processed for double immunofluorescence using anibodies against SP and NOS. Immunofluorescence staining in the even-numbered ganglia nodes showed the presence of FB-positive cells expressing SP (45,9 ± 3,38% in rNG and 60,4 ± 1,71% in lNG), and nNOS (34,9 ± 6,83% in rNG and 49,9 ± 9,32% in lNG). In HCL group increased expression of both SP (54,8 ± 5,34% in rNG and 56,9 ± 3,28 % in lNG) as well as nNOS (54,9 ± 4,45% in rNG and 52,5 ± 2,17 % in lNG) in FB+ perikaria was found. The acquired results suggest that SP and nNOS are neurotransmitters and/ or neuromodulators participating in the sensory regulation of the prepyloric region of porcine stomach function as well as their potential role in development of the stomach inflamatory state.

Keywords: nNOS, nodose ganglion, pig, SP

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