Search results for: ROCK signaling

Authors: Hadi Farhadian, Homayoon Katibeh

Abstract:

Groundwater inflow to the tunnels is one of the most important problems in tunneling operation. The objective of this study is the investigation of model dimension effects on tunnel inflow assessment in discontinuous rock masses using numerical modeling. In the numerical simulation, the model dimension has an important role in prediction of water inflow rate. When the model dimension is very small, due to low distance to the tunnel border, the model boundary conditions affect the estimated amount of groundwater flow into the tunnel and results show a very high inflow to tunnel. Hence, in this study, the two-dimensional universal distinct element code (UDEC) used and the impact of different model parameters, such as tunnel radius, joint spacing, horizontal and vertical model domain extent has been evaluated. Results show that the model domain extent is a function of the most significant parameters, which are tunnel radius and joint spacing.

Keywords: water inflow, tunnel, discontinues rock, numerical simulation

Procedia PDF Downloads 496

Authors: Mohamed Dhaoui, Hakim Gabtni

Abstract:

The migration of hydrocarbons is a fairly complicated process that depends on several parameters, both structural and sedimentological. In this study, we will try to determine secondary migration paths which convey hydrocarbon from their main source rock to the largest reservoir of the Paleozoic petroleum system of the Tunisian part of Ghadames basin. In fact, The Silurian source rock is the main source rock of the Paleozoic petroleum system of the Ghadames basin. However, the most solicited reservoir in this area is the Triassic reservoir TAGI (Trias Argilo-Gréseux Inférieur). Several geochemical studies have confirmed that oil products TAGI come mainly from the Tannezuft Silurian source rock. That being said that secondary migration occurs through the fault system which affects the post-Silurian series. Our study is based on analysis and interpretation of gravity data. The gravity modeling was conducted in the northern part of Ghadames basin and the Telemzane uplift. We noted that there is a close relationship between the location of producing oil fields and gravity gradients which separate the positive and negative gravity anomalies. In fact, the analysis and transformation of the Bouguer anomaly map, and the residual gravity map allowed as understanding the architecture of the Precambrian in the study area, thereafter gravimetric models were established allowed to determine the probable migration path.

Keywords: basement, Ghadames, gravity, hydrocarbon, migration path

Procedia PDF Downloads 325

Authors: Neil Bar, Andrew Heweston

Abstract:

Probability of failure (PF) often appears alongside factor of safety (FS) in design acceptance criteria for rock slope, underground excavation and open pit mine designs. However, the design acceptance criteria generally provide no guidance relating to how PF should be calculated for homogeneous and heterogeneous rock masses, or what qualifies a ‘reasonable’ PF assessment for a given slope design. Observational and kinematic methods were widely used in the 1990s until advances in computing permitted the routine use of numerical modelling. In the 2000s and early 2010s, PF in numerical models was generally calculated using the point estimate method. More recently, some limit equilibrium analysis software offer statistical parameter inputs along with Monte-Carlo or Latin-Hypercube sampling methods to automatically calculate PF. Factors including rock type and density, weathering and alteration, intact rock strength, rock mass quality and shear strength, the location and orientation of geologic structure, shear strength of geologic structure and groundwater pore pressure influence the stability of rock slopes. Significant engineering and geological judgment, interpretation and data interpolation is usually applied in determining these factors and amalgamating them into a geotechnical model which can then be analysed. Most factors are estimated ‘approximately’ or with allowances for some variability rather than ‘exactly’. When it comes to numerical modelling, some of these factors are then treated deterministically (i.e. as exact values), while others have probabilistic inputs based on the user’s discretion and understanding of the problem being analysed. This paper discusses the importance of understanding the key aspects of slope design for homogeneous and heterogeneous rock masses and how they can be translated into reasonable PF assessments where the data permits. A case study from a large open pit gold mine in a complex geological setting in Western Australia is presented to illustrate how PF can be calculated using different methods and obtain markedly different results. Ultimately sound engineering judgement and logic is often required to decipher the true meaning and significance (if any) of some PF results.

Keywords: probability of failure, point estimate method, Monte-Carlo simulations, sensitivity analysis, slope stability

Procedia PDF Downloads 189

Authors: Muhammad Munawar

Abstract:

Pavement destruction is normally associated with the horizontal relocation of subgrade because of pavement engrossing water and inordinate avoidance and differential settlement of material underneath the pavement. The aim of the research is to study the effect of the additives (rockdust) on the stability and the increase of bearing capacity of selected soils in Mardan City. The physical, chemical and designing properties of soil were contemplated, and the soil was treated with added admixture rockdust with the goal of stabilizing the local soil. The stabilization or modification of soil is done by blending of rock dust to soils in the scope of 0 to 85% by the rate increment of 5%, 10%, and 15% individually. The following test was done for treated sample: Atterberg limits (liquid limit, plasticity index, plastic limit), standard compaction test, the California bearing test and the direct shear test. The results demonstrated that the gradation of soil is narrow from the particle size analysis. Plasticity index (P.I), Liquid limit (L.L) and plastic limit (P.L) were shown reduction with the addition of Rock dust. It was concluded that the maximum dry density is increasing with the addition of rockdust up to 10%, beyond 10%, it shows reduction in their content. It was discovered that the Cohesion C diminished, the angle of internal friction and the California bearing ratio (C.B.R) was improved with the addition of Rock dust. The investigation demonstrated that the best stabilizer for the contextual investigation (Toru road Mardan) is the rock dust and the ideal dosage is 10 %.

Keywords: rockdust, stabilization, modification, CBR

Procedia PDF Downloads 252

Authors: Ojas Chaudhari, Ali Nejad Ghafar, Giedrius Zirgulis, Marjan Mousavi, Tommy Ellison, Sandra Pousette, Patrick Fontana

Abstract:

In Swedish tunnel construction, a critical issue that has been repeatedly acknowledged is corrosion and, consequently, failure of the rock bolts in rock support systems. The defective installation of rock bolts results in the formation of cavities in the cement mortar that is regularly used to fill the area under the dome plates. These voids allow for water-ingress to the rock bolt assembly, which results in corrosion of rock bolt components and eventually failure. In addition, the current installation technique consists of several manual steps with intense labor works that are usually done in uncomfortable and exhausting conditions, e.g., under the roof of the tunnels. Such intense tasks also lead to a considerable waste of materials and execution errors. Moreover, adequate quality control of the execution is hardly possible with the current technique. To overcome these issues, a non-shrinking/expansive cement-based mortar filled in the paper packaging has been developed in this study which properly fills the area under the dome plates without or with the least remaining cavities, ultimately that diminishes the potential of corrosion. This article summarizes the development process and the experimental evaluation of this technique for the installation of rock bolts. In the development process, the cementitious mortar was first developed using specific cement and shrinkage reducing/expansive additives. The mechanical and flow properties of the mortar were then evaluated using compressive strength, density, and slump flow measurement methods. In addition, isothermal calorimetry and shrinkage/expansion measurements were used to elucidate the hydration and durability attributes of the mortar. After obtaining the desired properties in both fresh and hardened conditions, the developed dry mortar was filled in specific permeable paper packaging and then submerged in water bath for specific intervals before the installation. The tests were enhanced progressively by optimizing different parameters such as shape and size of the packaging, characteristics of the paper used, immersion time in water and even some minor characteristics of the mortar. Finally, the developed prototype was tested in a lab-scale rock bolt assembly with various angles to analyze the efficiency of the method in real life scenario. The results showed that the new technique improves the performance of the rock bolts by reducing the material wastage, improving environmental performance, facilitating and accelerating the labor works, and finally enhancing the durability of the whole system. Accordingly, this approach provides an efficient alternative for the traditional way of tunnel bolt installation with considerable advantages for the Swedish tunneling industry.

Keywords: corrosion, durability, mortar, rock bolt

Procedia PDF Downloads 86

Authors: Cecilia Jatu, Adventino

Abstract:

Gedangsari is located in Gunungkidul, Yogyakarta Province, which has several criteria to be used as a new geosite object. The research area is located in the southern mountain zone of Java, composed of 5 rock formations with Oligocene up to Middle Miocene age. The purpose of this study is to reveal the potential of geotourism and the geoheritage to be proposed as a new geosite and to make a geosite map of Gedangsari. The research method used is descriptive data collection and which includes quantitative geological data collection, geotourism, and heritage sites, then supported by petrographic analysis, geological structure, geological mapping, and SWOT analysis. The geological data proved that Gedangsari consists of igneous rock (intrusion), pyroclastic rock, and sediment rock. This condition caused many varieties and particular geomorphological platform. Geotourism that include in Gedangsari are Luweng Sampang Canyon, Gedangsari Bouma Sequence, Watugajah Columnar Joint, Gedangsari Marine Fan Sediment, and Tegalrejo Waterfall. There is also Tegalrejo Village, which can be considered as geoheritage site because of its culture and batik traditional cloth. The results of the SWOT analysis, Gedangsari geosite must be developed and appropriately promoted in order to improve the existence. The development of geosite area will have a significant impact that improve the economic growth of the surrounding community and can be used by the government as base information for sustainable development. In addition, the making of an educational map about the geological conditions and geotourism location of the Gedangsari geosite can increase the people's knowledge about Gedangsari.

Keywords: Gedangsari, geoheritage, geotourism, geosite

Procedia PDF Downloads 96

Authors: Rueyhung Weng, Chia-En Huang, Jung-Chi-Liao

Abstract:

The transition zone (TZ) serves as a diffusion barrier to regulate the ins and outs of the proteins recruited to the primary cilia. TCTN2 is one of the TZ proteins and its mutation causes Joubert syndrome, a serious multi-organ disease. Despite its important medical relevance, the functions of TCTN2 remain elusive. Here we created a TCTN2 gene deleted retinal pigment epithelial cells (RPE1) using CRISPR/Cas9-based genome editing technique and used this knockout line to reveal roles of TCTN2. TCTN2 knockout RPE1 cells displayed a significantly reduced ciliogenesis or a shortened primary cilium length in the cilium-remaining population. Intraflagellar transport protein IFT88 aberrantly accumulated at the tip of TCTN2 deficient cells. Guanine nucleotide exchange factor Arl13B was mostly absent from the ciliary compartment, with a small population localizing at the ciliary tip. The deficient TZ was corroborated with the mislocalization of two other TZ proteins TMEM67 and MKS1. In addition, TCTN2 deficiency induced TZ impairment led to the suppression of Sonic hedgehog signaling in response to Smoothened (Smo) agonist. Together, depletion of TCTN2 destabilizes other TZ proteins and considerably alters the localization of key transport and signaling-associated proteins, including IFT88, Arl13B, and Smo.

Keywords: CRISPR/Cas9, primary cilia, Sonic hedgehog signaling, transition zone

Procedia PDF Downloads 313

Authors: Bing Yan

Abstract:

Nanomaterials are widely used in various industrial sectors, biomedicine, and more than 1300 consumer products. Although there is still no standard safety regulation, their potential toxicity is a major concern worldwide. We discovered that nanoparticles target and enter human cells1, perturb cellular signaling pathways2, affect various cell functions3, and cause malfunctions in animals4,5. Because the majority of atoms in nanoparticles are on the surface, chemistry modification on their surface may change their biological properties significantly. We modified nanoparticle surface using nano-combinatorial chemistry library approach6. Novel nanoparticles were discovered to exhibit significantly reduced toxicity6,7, enhance cancer targeting ability8, or re-program cellular signaling machineries7. Using computational chemistry, quantitative nanostructure-activity relationship (QNAR) is established and predictive models have been built to predict biocompatible nanoparticles.

Keywords: nanoparticle, nanotoxicity, nano-bio, nano-combinatorial chemistry, nanoparticle library

Procedia PDF Downloads 374

Authors: Blanche Aguida, Marootpong Pooam, Nathalie Jourdan, Margaret Ahmad

Abstract:

COVID-19-related morbidity is associated with exaggerated inflammation and cytokine production in the lungs, leading to acute respiratory failure. The cellular mechanisms underlying these so-called ‘cytokine storms’ are regulated through the Toll-like receptor 4 (TLR4) signaling pathway and by reactive oxygen species (ROS). Both light (photobiomodulation) and magnetic fields (e.g., pulsed electromagnetic field) stimulation are non-invasive therapies known to confer anti-inflammatory effects and regulate ROS signaling pathways. Here we show that daily exposure to two 10-minute intervals of moderate-intensity infra-red light significantly lowered the inflammatory response induced via the TLR4 receptor signaling pathway in human cell cultures. Anti-inflammatory effects were likewise achieved by electromagnetic field exposure of cells to daily 10-minute intervals of either pulsed electromagnetic fields (PEMF) or to low-level static magnetic fields. Because current illumination and electromagnetic field therapies have no known side effects and are already approved for some medical uses, we have here developed protocols for verification in clinical trials of COVID 19 infection. These treatments are affordable, simple to implement, and may help to resolve the acute respiratory distress of COVID 19 patients both in the home and in the hospital.

Keywords: COVID 19, electromagnetic fields therapy, inflammation, photobiomodulation therapy

Procedia PDF Downloads 119

Authors: M. Cardenas-Garcia, P. P. Gonzalez-Perez

Abstract:

Intercellular communication is a necessary condition for cellular functions and it allows a group of cells to survive as a population. Throughout this interaction, the cells work in a coordinated and collaborative way which facilitates their survival. In the case of cancerous cells, these take advantage of intercellular communication to preserve their malignancy, since through these physical unions they can send signs of malignancy. The Wnt/β-catenin signaling pathway plays an important role in the formation of intercellular communications, being also involved in a large number of cellular processes such as proliferation, differentiation, adhesion, cell survival, and cell death. The modeling and simulation of cellular signaling systems have found valuable support in a wide range of modeling approaches, which cover a wide spectrum ranging from mathematical models; e.g., ordinary differential equations, statistical methods, and numerical methods– to computational models; e.g., process algebra for modeling behavior and variation in molecular systems. Based on these models, different simulation tools have been developed from mathematical ones to computational ones. Regarding cellular and molecular processes in cancer, its study has also found a valuable support in different simulation tools that, covering a spectrum as mentioned above, have allowed the in silico experimentation of this phenomenon at the cellular and molecular level. In this work, we simulate and explore the complex interaction patterns of intercellular communication in cancer cells using the Cellulat bioinformatics tool, a computational simulation tool developed by us and motivated by two key elements: 1) a biochemically inspired model of self-organizing coordination in tuple spaces, and 2) the Gillespie’s algorithm, a stochastic simulation algorithm typically used to mimic systems of chemical/biochemical reactions in an efficient and accurate way. The main idea behind the Cellulat simulation tool is to provide an in silico experimentation environment that complements and guides in vitro experimentation in intra and intercellular signaling networks. Unlike most of the cell signaling simulation tools, such as E-Cell, BetaWB and Cell Illustrator which provides abstractions to model only intracellular behavior, Cellulat is appropriate for modeling both intracellular signaling and intercellular communication, providing the abstractions required to model –and as a result, simulate– the interaction mechanisms that involve two or more cells, that is essential in the scenario discussed in this work. During the development of this work we made evident the application of our computational simulation tool (Cellulat) for the modeling and simulation of intercellular communication between normal and cancerous cells, and in this way, propose key molecules that may prevent the arrival of malignant signals to the cells that surround the tumor cells. In this manner, we could identify the significant role that has the Wnt/β-catenin signaling pathway in cellular communication, and therefore, in the dissemination of cancer cells. We verified, using in silico experiments, how the inhibition of this signaling pathway prevents that the cells that surround a cancerous cell are transformed.

Keywords: cancer cells, in silico approach, intercellular communication, key molecules, modeling and simulation

Procedia PDF Downloads 228

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

Abstract:

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

Procedia PDF Downloads 65

Authors: B. Bahloul, K. Babesse, A. Dkhira, Y. Bahloul, L. Amirouche

Abstract:

Structural and electronic properties of the rock-salt BaxSr1−xS are calculated using the first-principles calculations based on the density functional theory (DFT) within the generalized gradient approximation (GGA), the local density approximation (LDA) and the virtual-crystal approximation (VCA). The calculated lattice parameters at equilibrium volume for x=0 and x=1 are in good agreement with the literature data. The BaxSr1−xS alloys are found to be an indirect band gap semiconductor. Moreoever, for the composition (x) ranging between [0-1], we think that our results are well discussed and well predicted.

Keywords: semiconductor, Ab initio calculations, rocksalt, band structure, BaxSr1−xS

Procedia PDF Downloads 365

Authors: Kanupreiya, Rajani Sharma

Abstract:

Construction of a single underground structure is itself a challenging task, and it becomes more critical in tectonically active young mountains such as the Himalayas which are highly anisotropic. The Himalayan geology mostly comprises of incompetent and sheared rock mass in addition to fold/faults, rock burst, and water ingress. Underground tunnels form the most essential and important structure in run-of-river hydroelectric projects. Punatsangchhu I hydroelectric project (PHEP-I), Bhutan (1200 MW) is a run-of-river scheme which has four parallel underground desilting chambers. The Punatsangchhu River carries a large quantity of silt load during monsoon season. Desilting chambers were provided to remove the silt particles of size greater than and equal to 0.2 mm with 90% efficiency, thereby minimizing the rate of damage to turbines. These chambers are 330 m long, 18 m wide at the center and 23.87 m high, with a 5.87 m hopper portion. The geology of desilting chambers was known from an exploratory drift which exposed low dipping foliation joint and six joint sets. The RMR and Q value in this reach varied from 40 to 60 and 1 to 6 respectively. This paper describes different rock engineering principles undertaken for safe excavation and rock support of the moderately jointed, blocky and thinly foliated biotite gneiss. For the design of rock support system of desilting chambers, empirical and numerical analysis was adopted. Finite element analysis was carried out for cavern design and finalization of pillar width using Phase2. Phase2 is a powerful tool for simulation of stage-wise excavation with simultaneous provision of support system. As the geology of the region had 7 sets of joints, in addition to FEM based approach, safety factors for potentially unstable wedges were checked using UnWedge. The final support recommendations were based on continuous face mapping, numerical modelling, empirical calculations, and practical experiences.

Keywords: dam siltation, Himalayan geology, hydropower, rock support, numerical modelling

Procedia PDF Downloads 72

Authors: Ndivhudzannyi Rembuluwani, Francis Dacosta, Emmanuel Mhlongo

Abstract:

The small-scale rock aggregate sector of the mining industry is a major source of employment for a significant number of people, particularly in remote rural areas, where alternative livelihoods are rare. It contributes to local economy by generating income and producing major and essential materials for the building, construction, and other industries. However, the sector is confronted with many challenges that hamper productivity and growth. The problems that confront this sector includes: health and safety, environmental impacts, low production and low adherence to mining legislations. This study investigated the challenges confronting selected small-scale rock aggregate mines in the Vhembe District of Limpopo province of South Africa, assesses the health, safety, low production and environmental impacts associated with aggregate production and to develop an integrated approach of addressing the multi-faceted challenges.

Keywords: health and safety, legislative framework, productivity, rock aggregate, small-scale mining

Procedia PDF Downloads 457

Authors: Michal Kielbik, Izabela Szulc-Kielbik, Anna Brzostek, Jaroslaw Dziadek, Magdalena Klink

Abstract:

The goal of many research groups in the world is to find new components that are important for survival of mycobacteria in the host cells. Mycobacterium tuberculosis (Mtb) possesses a number of enzymes degrading cholesterol that are considered to be an important factor for its survival and persistence in host macrophages. One of them - cholesterol oxidase (ChoD), although not being essential for cholesterol degradation, is discussed as a virulence compound, however its involvement in macrophages’ response to Mtb is still not sufficiently determined. The recognition of tubercle bacilli antigens by pathogen recognition receptors is crucial for the initiation of the host innate immune response. An important receptor that has been implicated in the recognition and/or uptake of Mtb is Toll-like receptor type 2 (TLR2). Engagement of TLR2 results in the activation and phosphorylation of intracellular signaling proteins including IRAK-1 and -4, TRAF-6, which in turn leads to the activation of target kinases and transcription factors responsible for bactericidal and pro-inflammatory response of macrophages. The aim of these studies was a detailed clarification of the role of Mtb cholesterol oxidase as a virulence factor affecting the TLR2 signaling pathway in human macrophages. As human macrophages the THP-1 differentiated cells were applied. The virulent wild-type Mtb strain (H37Rv), its mutant lacking a functional copy of gene encoding cholesterol oxidase (∆choD), as well as complimented strain (∆choD–choD) were used. We tested the impact of Mtb strains on the expression of TLR2-depended signaling proteins (mRNA level, cytosolic level and phosphorylation status). The cytokine and bactericidal response of THP-1 derived macrophages infected with Mtb strains in relation to TLR2 signaling pathway dependence was also determined. We found that during the 24-hours of infection process the wild-type and complemented Mtb significantly reduced the cytosolic level and phosphorylation status of IRAK-4 and TRAF-6 proteins in macrophages, that was not observed in the case of ΔchoD mutant. Decreasement of TLR2-dependent signaling proteins, induced by wild-type Mtb, was not dependent on the activity of proteasome. Blocking of TLR2 expression, before infection, effectively prevented the induced by wild-type strain reduction of cytosolic level and phosphorylation of IRAK-4. None of the strains affected the surface expression of TLR2. The mRNA level of IRAK-4 and TRAF-6 genes were significantly increased in macrophages 24 hours post-infection with either of tested strains. However, the impact of wild-type Mtb strain on both examined genes was significantly stronger than its ΔchoD mutant. We also found that wild-type strain stimulated macrophages to release high amount of immunosuppressive IL-10, accompanied by low amount of pro-inflammatory IL-8 and bactericidal nitric oxide in comparison to mutant lacking cholesterol oxidase. The influence of wild-type Mtb on this type of macrophages' response strongly dependent on fully active IRAK-1 and IRAK-4 signaling proteins. In conclusion, Mtb using cholesterol oxidase causes the over-activation of TLR2 signaling proteins leading to the reduction of their cytosolic level and activity resulting in the modulation of macrophages response to allow its intracellular survival. Supported by grant: 2014/15/B/NZ6/01565, National Science Center, Poland

Keywords: Mycobacterium tuberculosis, cholesterol oxidase, macrophages, TLR2-dependent signaling pathway

Procedia PDF Downloads 395

Authors: Norbert Simon, Rodeano Roslee, Abdul Ghani Rafek, Goh Thian Lai, Azimah Hussein, Lee Khai Ern

Abstract:

The 54 km stretch of Ranau-Tambunan (RTM) road in Sabah is subjected to slope failures almost every year. This study is focusing on identifying section of roads that are susceptible to failure based on temporal landslide density and lineament density analyses. In addition to the analyses, the rock slopes in several sections of the road were assessed using the geological strength index (GSI) technique. The analysis involved 148 landslides that were obtained in 1978, 1994, 2009 and 2011. The landslides were digitized as points and the point density was calculated based on every 1km2 of the road. The lineaments of the area was interpreted from Landsat 7 15m panchromatic band. The lineament density was later calculated based on every 1km2 of the area using similar technique with the slope failure density calculation. The landslide and lineament densities were classified into three different classes that indicate the level of susceptibility (low, moderate, high). Subsequently, the two density maps were overlap to produce the final susceptibility map. The combination of both high susceptibility classes from these maps signifies the high potential of slope failure in those locations in the future. The final susceptibility map indicates that there are 22 sections of the road that are highly susceptible. Seven rock slopes were assessed along the RTM road using the GSI technique. It was found from the assessment that rock slopes along this road are highly fractured, weathered and can be classified into fair to poor categories. The poor condition of the rock slope can be attributed to the high lineament density that presence in the study area. Six of the rock slopes are located in the high susceptibility zones. A detailed investigation on the 22 high susceptibility sections of the RTM road should be conducted due to their higher susceptibility to failure, in order to prevent untoward incident to road users in the future.

Keywords: GSI, landslide, landslide density, landslide susceptibility, lineament density

Procedia PDF Downloads 367

Authors: Sara Mercedes Barroso Pinzón, Antonio Javier Sanchéz Herencia, Begoña Ferrari, Álvaro Jesús Castro

Abstract:

The current need for durable implants and bone substitutes characterised by biocompatibility, bioactivity and mechanical properties, without immunological rejection, is a major challenge for scientists. Hydroxyapatite (HAp) has been considered for decades as an ideal biomaterial for bone regeneration due to its chemical and crystallographic similarity to the mineral structure bioapatites. However, the lack of trace elements in the hydroxyapatite structure gives it very low mechanical and biological properties. In this sense, the objective of the research is to address the synthesis of hydroxyapatite with Mg from phosphate rock from sedimentary deposits in the central-eastern region of Colombia, taking advantage of the release of the species contained as natural precursors of Ca, P and Mg. The minerals present were studied, fluorapatite as the mineral of interest associated with mineralogical species of magnesium carbonates and quartz. The chemical and mineralogical composition was determined by X-ray fluorescence (XRF) and X-ray diffraction (XRD), scanning electron microscopy (SEM) and energy dispersive X-ray spectroscopy (EDX); as well as the evaluation of the surface physicochemical properties of zeta potential (PZC), with the aim of studying the surface behaviour of the microconstituents present in the phosphate rock and to elucidate the synergistic mechanism between the minerals and establish the optimum conditions for the wet concentration process. From the products obtained and characterised by XRD, XRF, SEM, FTIR, RAMAN, HAp-Mg biocomposite scaffolds are fabricated and the influence of Mg on the morphometric parameters, mechanical and biological properties of the designed materials is evaluated.

Keywords: phosphate rock, hydroxyapatite, magnesium, biomaterials

Procedia PDF Downloads 17

Authors: Modreck Gomo

Abstract:

The evolution of groundwater chemistry and its quality is largely controlled by hydrogeochemical processes and their understanding is therefore important for groundwater quality assessments and protection of the water resources. A study was conducted in Bloemfontein town of South Africa to assess and compare the groundwater chemistry and quality characteristics in an alluvial aquifer and single-plane fractured-rock aquifers. 9 groundwater samples were collected from monitoring boreholes drilled into the two aquifer systems during a once-off sampling exercise. Samples were collected through low-flow purging technique and analysed for major ions and trace elements. In order to describe the hydrochemical facies and identify dominant hydrogeochemical processes, the groundwater chemistry data are interpreted using stiff diagrams and principal component analysis (PCA), as complimentary tools. The fitness of the groundwater quality for domestic and irrigation uses is also assessed. Results show that the alluvial aquifer is characterised by a Na-HCO₃ hydrochemical facie while fractured-rock aquifer has a Ca-HCO₃ facie. The groundwater in both aquifers originally evolved from the dissolution of calcite rocks that are common on land surface environments. However the groundwater in the alluvial aquifer further goes through another evolution as driven by cation exchange process in which Na in the sediments exchanges with Ca²⁺ in the Ca-HCO₃ hydrochemical type to result in the Na-HCO₃ hydrochemical type. Despite the difference in the hydrogeochemical processes between the alluvial aquifer and single-plane fractured-rock aquifer, this did not influence the groundwater quality. The groundwater in the two aquifers is very hard as influenced by the elevated magnesium and calcium ions that evolve from dissolution of carbonate minerals which typically occurs in surface environments. Based on total dissolved levels (600-900 mg/L), groundwater quality of the two aquifer systems is classified to be of fair quality. The negative potential impacts of the groundwater quality for domestic uses are highlighted.

Keywords: alluvial aquifer, fractured-rock aquifer, groundwater quality, hydrogeochemical processes

Procedia PDF Downloads 168

Authors: Chang-Bin Ha, Young-Min Ko, Seongjoo Lee, Hyoung-Kyu Song

Abstract:

In this paper, the signaling scheme using phase shifting is proposed for the improved performance of the Wi-Fi backscatter system. Because the communication in the Wi-Fi backscatter system is based on on-off modulation and impedance modulation by unit of packet, the data rate is very low compared to the conventional wireless systems. Also, because the Wi-Fi backscatter system is based on the RF-powered device, the achievement of high reliability is difficult. In order to increase the low data rate, the proposed scheme transmits information of multiple bits during one packet period. Also, in order to increase the reliability, the proposed scheme shifts the phase of signal in according to the transmitting information. The simulation result shows that the proposed scheme has the improved throughput performance.

Keywords: phase shifting, RF-powered device, Wi-Fi backscatter system, IoT

Procedia PDF Downloads 412

Authors: Jiangang Shen

Abstract:

Olfactory dysfunction is a common symptom companied by anxiety- and depressive-like behaviors in depressive patients. Chronic stress triggers hormone responses and inhibits the proliferation and differentiation of neural stem cells (NSCs) in the hippocampus and subventricular zone (SVZ)-olfactory bulb (OB), contributing to depressive behaviors and olfactory dysfunction. However, the cellular signaling molecules to regulate chronic stress mediated olfactory dysfunction are largely unclear. Adaptor proteins containing the pleckstrin homology domain, phosphotyrosine binding domain, and leucine zipper motif (APPLs) are multifunctional adaptor proteins. Herein, we tested the hypothesis that APPL2 could inhibit hippocampal neurogenesis by affecting glucocorticoid receptor (GR) signaling, subsequently contributing to depressive and anxiety behaviors as well as olfactory dysfunctions. The major discoveries are included: (1) APPL2 Tg mice had enhanced GR phosphorylation under basic conditions but had no different plasma corticosterone (CORT) level and GR phosphorylation under stress stimulation. (2) APPL2 Tg mice had impaired hippocampal neurogenesis and revealed depressive and anxiety behaviors. (3) GR antagonist RU486 reversed the impaired hippocampal neurogenesis in the APPL2 Tg mice. (4) APPL2 Tg mice displayed higher GR activity and less capacity for neurogenesis at the olfactory system with lesser olfactory sensitivity than WT mice. (5) APPL2 negatively regulates olfactory functions by switching fate commitments of NSCs in adult olfactory bulbs via interaction with Notch1 signaling. Furthermore, baicalin, a natural medicinal compound, was found to be a promising agent targeting APPL2/GR signaling and promoting adult neurogenesis in APPL2 Tg mice and chronic corticosterone-induced depression mouse models. Behavioral tests revealed that baicalin had antidepressant and olfactory-improving effects. Taken together, APPL2 is a critical therapeutic target for antidepressant treatment.

Keywords: APPL2, hippocampal neurogenesis, depressive behaviors and olfactory dysfunction, stress

Procedia PDF Downloads 49

Authors: M. A. Rashed, A. S. Mansour, H. Faris, W. Afify

Abstract:

The calcarenites carbonate rocks of the Quaternary ridges, which extend along the northwestern Mediterranean coastal plain of Egypt, represent an excellent model for the transformation of loose sediments to real sedimentary rocks by the different stages of meteoric diagenesis. The depositional and diagenetic fabrics of the rocks, in addition to the strata orientation, highly affect their ultimate compressive strength and other geotechnical properties. There is a marked increase in the compressive strength (UCS) from the first to the fourth ridge rock samples. The lowest values are related to the loose packing, weakly cemented aragonitic ooid sediments with high porosity, besides the irregularly distributed of cement, which result in decreasing the ability of these rocks to withstand crushing under direct pressure. The high (UCS) values are attributed to the low porosity, the presence of micritic cement, the reduction in grain size and the occurrence of micritization and calcretization processes. The strata orientation has a notable effect on the measured (UCS). The lowest values have been recorded for the samples cored in the inclined direction; whereas the highest values have been noticed in most samples cored in the vertical and parallel directions to bedding plane. In case of the inclined direction, the bedding planes were oriented close to the plane of maximum shear stress. The lowest and highest anisotropy values have been recorded for the first and the third ridges rock samples, respectively, which may attributed to the relatively homogeneity and well sorted grain-stone of the first ridge rock samples, and relatively heterogeneity in grain and pore size distribution and degree of cementation of the third ridge rock samples, besides, the abundance of shell fragments with intra-particle pore spaces, which may produce lines of weakness within the rock.

Keywords: compressive strength, anisotropy, calcarenites, Egypt

Procedia PDF Downloads 346

Authors: Mohammad Moridzadeh, Aaron Gallant

Abstract:

The paper will present the design and construction of the underground excavations of a pump station forebay and its related components including connector tunnels, access shaft, riser shaft and well shafts. The underground openings include an 8 m-diameter riser shaft, an 8-m-diameter access shaft, 34 2.4-m-diameter well shafts, a 107-m-long forebay with a cross section having a height of 11 m and width of 10 m, and a 6 m by 6 m stub connector tunnel between the access shaft and a future forebay extension. The riser shaft extends down from the existing forebay connector tunnel at elevation 247 m to the crown of the forebay at elevation 770.0 feet. The access shaft will extend from the platform at the surface down to El. 223.5 m. The pump station will have the capacity to deliver 600 million gallons per day. The project is located on an uplifted horst consisting of a mass of Precambrian metamorphic rock trending in a north-south direction. The eastern slope of the area is very steep and pronounced and is likely the result of high-angle normal faulting. Toward the west, the area is bordered by a high angle normal fault and recent alluvial, lacustrine, and colluvial deposits. An evaluation of rock mass properties, fault and discontinuities, foliation and joints, and in situ stresses was performed. The response of the rock mass was evaluated in 3DEC using Discrete Element Method (DEM) by explicitly accounting for both major and minor discontinuities within the rock mass (i.e. joints, shear zones, faults). Moreover, the stability of the entire subsurface structure including the forebay, access and riser shafts, future forebay, well shafts, and connecting tunnels and their interactions with each other were evaluated using a 3D coupled hydromechanical Finite Element Analysis (FEA).

Keywords: coupled hydromechanical analysis, discontinuities, discrete element, finite element, pump station

Procedia PDF Downloads 240

Authors: Mehmet Salih Bayraktutan

Abstract:

Geomechanical properties of Rock Salt Deposits in Tuzluca Salt Mine Area (Eastern Turkey) are studied for modeling the operation- excavation strategy. The purpose of this research focused on calculating the critical value of span height- which will meet the safety requirements. The Mine Site Tuzluca Hills consist of alternating parallel bedding of Salt ( NaCl ) and Gypsum ( CaS04 + 2 H20) rocks. Rock Salt beds are more resistant than narrow Gypsum interlayers. Rock Salt beds formed almost 97 percent of the total height of the Hill. Therefore, the geotechnical safety of Galleries depends on the mechanical criteria of Rock Salt Cores. General deposition of Tuzluca Basin was finally completed by Tuzluca Evaporites, as for the uppermost stratigraphic unit. They are currently running mining operations performed by classic mechanical excavation, room and pillar method. Rooms and Pillars are currently experiencing an initial stage of fracturing in places. Geotechnical safety of the whole mining area evaluated by Rock Mass Rating (RMR), Rock Quality Designation (RQD) spacing of joints, and the interaction of groundwater and fracture system. In general, bedded rock salt Show large lateral deformation capacity (while deformation modulus stays in relative small values, here E= 9.86 GPa). In such litho-stratigraphic environments, creep is a critical mechanism in failure. Rock Salt creep rate in steady-state is greater than interbedding layers. Under long-lasted compressive stresses, creep may cause shear displacements, partly using bedding planes. Eventually, steady-state creep in time returns to accelerated stages. Uniaxial compression creep tests on specimens were performed to have an idea of rock salt strength. To give an idea, on Rock Salt cores, average axial strength and strain are found as 18 - 24 MPa and 0.43-0.45 %, respectively. Uniaxial Compressive strength of 26- 32 MPa, from bedded rock salt cores. Elastic modulus is comparatively low, but lateral deformation of the rock salt is high under the uniaxial compression stress state. Poisson ratio = 0.44, break load = 156 kN, cohesion c= 12.8 kg/cm2, specific gravity SG=2.17 gr/cm3. Fracture System; spacing of fractures, joints, faults, offsets are evaluated under acting geodynamic mechanism. Two sand beds, each 4-6 m thick, exist near to upper level and at the top of the evaporating sequence. They act as aquifers and keep infiltrated water on top for a long duration, which may result in the failure of roofs or pillars. Two major active seismic ( N30W and N70E ) striking Fault Planes and parallel fracture strands have seismically triggered moderate risk of structural deformation of rock salt bedding sequence. Earthquakes and Floods are two prevailing sources of geohazards in this region—the seismotectonic activity of the Mine Site based on the crossing framework of Kagizman Faults and Igdir Faults. Dominant Hazard Risk sources include; a) Weak mechanical properties of rock salt, gypsum, anhydrite beds-creep. b) Physical discontinuities cutting across the thick parallel layers of Evaporite Mass, c) Intercalated beds of weak cemented or loose sand, clayey sandy sediments. On the other hand, absorbing the effects of salt-gyps parallel bedded deposits on seismic wave amplitudes has a reducing effect on the Rock Mass.

Keywords: bedded rock salt, creep, failure mechanism, geotechnical safety

Procedia PDF Downloads 167

Authors: Ireneusz Majsterek, Dariusz Pytel, J. Alan Diehl

Abstract:

PKR-like ER kinase (PERK) is serine/threonie endoplasmic reticulum (ER) transmembrane kinase activated during ER-stress. PERK can activate signaling pathways known as unfolded protein response (UPR). Attenuation of translation is mediated by PERK via phosphorylation of eukaryotic initiation factor 2α (eIF2α), which is necessary for translation initiation. PERK activation also directly contributes to activation of Nrf2 which regulates expression of anti-oxidant enzymes. An increased phosphorylation of eIF2α has been reported in Alzheimer disease (AD) patient hippocampus, indicating that PERK is activated in this disease. Recent data have revealed activation of PERK signaling in non-Hodgkins lymphomas. Results also revealed that loss of PERK limits mammary tumor cell growth in vitro and in vivo. Consistent with these observations, activation of UPR in vitro increases levels of the amyloid precursor protein (APP), the peptide from which beta-amyloid plaques (AB) fragments are derived. Finally, proteolytic processing of APP, including the cleavages that produce AB, largely occurs in the ER, and localization coincident with PERK activity. Thus, we expect that PERK-dependent signaling is critical for progression of many types of diseases (human cancer, neurodegenerative disease and other). Therefore, modulation of PERK activity may be a useful therapeutic target in the treatment of different diseases that fail to respond to traditional chemotherapeutic strategies, including Alzheimer’s disease. Our goal will be to developed therapeutic modalities targeting PERK activity.

Keywords: PERK kinase, small molecule inhibitor, neurodegenerative disease, Alzheimer’s disease

Procedia PDF Downloads 460

Authors: Ali Ozvan, Ismail Akkaya, Mucip Tapan

Abstract:

Travertine is generally a weak or medium strong rock, and physical, mechanical and structural properties of travertines are direct impacts on geotechnical studies. New settlement areas were determined on travertine units after two destructive earthquakes which occurred on October 23rd, 2011 (M=7.1) and November 9th, 2011 (M=5.6) in Tabanlı and Edremit districts of Van province in Turkey, respectively. In the study area, the travertines have different lithotype and engineering properties such as strong crystalline crust, medium strong shrub, and weak reed which can affect mechanical and engineering properties of travertine and each level have different handicaps. Travertine has a higher strength when compared to the soil ground; however, it can have different handicaps such as having poor rock mass, karst caves and weathering alteration. Physico-mechanical properties of travertine in the study area are determined by laboratory tests and field observations. Uniaxial compressive strength (UCS) values were detected by indirect methods, and the strength map of different lithotype of Edremit travertine was created in order to define suitable settlement areas. Also, rock mass properties and underground structure were determined by bore holes, field studies, and geophysical method. The reason of this study is to investigate the relationship between lithotype and physicomechanical properties of travertines. According to the results, lithotype has an effect on physical, mechanical and rock mass properties of travertine levels. It is detected by several research methods that various handicaps may occur on such areas when the active tectonic structure of the area is evaluated along with the karstic cavities within the travertine and different lithotype qualities.

Keywords: travertine, lithotype, geotechnical parameters, Van earthquake

Procedia PDF Downloads 204

Authors: Vladimir Vinnikov

Abstract:

The paper proposes a model of an inhomogeneous rock mass with initially random distribution of microcracks on mineral grain boundaries. It describes the behavior of cracks in a medium under the effect of thermal field, the medium heated instantaneously to a predetermined temperature. Crack growth occurs according to the concept of fracture mechanics provided that the stress intensity factor K exceeds the critical value of Kc. The modeling of thermally induced acoustic emission memory effects is based on the assumption that every event of crack nucleation or crack growth caused by heating is accompanied with a single acoustic emission event. Parameters of the thermally induced acoustic emission memory effect produced by cyclic heating and cooling (with the temperature amplitude increasing from cycle to cycle) were calculated for several rock texture types (massive, banded, and disseminated). The study substantiates the adaptation of the proposed model to humidity interference with the thermally induced acoustic emission memory effect. The influence of humidity on the thermally induced acoustic emission memory effect in quasi-homogeneous and banded rocks is estimated. It is shown that such modeling allows the structure and texture of rocks to be taken into account and the influence of interference factors on the distinctness of the thermally induced acoustic emission memory effect to be estimated. The numerical modeling can be used to obtain information about the thermal impacts on rocks in the past and determine the degree of rock disturbance by means of non-destructive testing.

Keywords: crack growth, cyclic heating and cooling, rock texture, thermo acoustic emission memory effect

Procedia PDF Downloads 248

Authors: Clarence Dissanayake, Anishka A. Hettiarachchi

Abstract:

Landscape architecture needs to encompass a placemaking process carefully composing and manipulating landscape elements to address perceptual needs of humans, especially aesthetic, psychological and spiritual. The objective of this qualitative investigation is to inquire the impact of elements of rock and water combination on landscape perception and related feelings, emotions, and behavior. The past empirical studies have assessed the impact of landscape elements in isolation on user preference, yet the combined effect of elements have been less considered. This research was conducted with reference to the verity of qualities of water and rock through a visual landscape quality assessment focusing on landscape qualities derived from five visual concepts (coherence, historicity imageability, naturalness, and ephemera). 'Kaludiya Pokuna' archeological site in Anuradhapura was investigated with a sample of University students (n=19, male 14, female 5, age 20-25) using a five-point Likert scale via a perception based questionnaire and a visitor employed photographic survey (VEP). Two hypothetical questions were taken into investigation concerning biophilic (naturalness) and topophilic (historicity) aspects of humans to prefer a landscape with rock and water. The findings revealed that this combination encourages both biophilic and topophilic aspects, but in varying degrees. The identified hierarchy of visual concepts based on visitor’s preference signify coherence (93%), historicity (89%), imageability (79%), naturalness (75%) and ephemera (70%) respectively. It was further revealed that this combination creates a scenery more coherent dominating information processing aspect of humans to perceive a landscape over the biophilic and topophilic aspects. Different characteristics and secondary landscape effects generated by rock and water combination were found to affect in transforming a space into a place, full filling the aesthetic and spiritual aspects of the visitors. These findings enhance a means of making places for people, resource management and historical landscape conservation. Equalization of gender based participation, taking diverse cases and increasing the sample size with more analytical photographic analysis are recommended to enhance the quality of further research.

Keywords: landscape perception, visitor’s preference, rock and water combination, visual concepts

Procedia PDF Downloads 193

Authors: Cahya Wimar Wicaksono, Reynara Davin Chen, Alvian Kristianto Santoso

Abstract:

Grasberg Cu-Au ore deposit as one of the biggest porphyry deposits located in Papua Province, Indonesia produced by several intrusion that restricted by Heavy Sulphide Zone (HSZ) in peripheral. HSZ is the rock that becomes the contact between Grassberg Igneous Complex (GIC) with sedimentary and igneous rock outside, which is rich in sulphide minerals such as pyrite ± pyrrhotite. This research is to obtain the characteristic of HSZ based on geotechnical, geochemical and mineralogy aspect and those implication for daily mining operational activities. Method used in this research are geological and alteration mapping, core logging, FAA (Fire Assay Analysis), AAS (Atomic absorption spectroscopy), RQD (Rock Quality Designation) and rock water content. Data generated from methods among RQD data, mineral composition and grade, lithological and structural geology distribution in research area. The mapping data show that HSZ material characteristics divided into three type based on rocks association, there are near igneous rocks, sedimentary rocks and on HSZ area. And also divided based on its location, north and south part of research area. HSZ material characteristic consist of rock which rich of pyrite ± pyrrhotite, and RQD range valued about 25%-100%. Pyrite ± pyrrhotite which outcropped will react with H₂O and O₂ resulting acid that generates corrosive effect on steel wire and rockbolt. Whereas, pyrite precipitation proses in HSZ forming combustible H₂S gas which is harmful during blasting activities. Furthermore, the impact of H₂S gas in blasting activities is forming poison gas SO₂. Although HSZ high grade Cu-Au, however those high grade Cu-Au rich in sulphide components which is affected in flotation milling process. Pyrite ± pyrrhotite in HSZ will chemically react with Cu-Au that will settle in milling process instead of floating.

Keywords: combustible, corrosive, heavy sulphide zone, pyrite ± pyrrhotite

Procedia PDF Downloads 305

Authors: Shih-Ping Liu, Cheng-Hsuan Chang, Yu-Chuen Huang, Shih-Yin Chen, Woei-Cherng Shyu

Abstract:

Embryonic stem cells (ES) and induced pluripotnet stem cells (iPS) are both pluripotent stem cells. For mouse stem cells culture technology, leukemia inhibitory factor (LIF) was used to maintain the pluripotency of stem cells in vitro. However, LIF is an expensive reagent. The goal of this study was to find out a pure compound extracted from Chinese herbal medicine that could maintain stem cells pluripotency to replace LIF and improve the iPS generation efficiency. From 20 candidates traditional Chinese medicine we found that Cordycepsmilitaris triggered the up-regulation of stem cells activating genes (Oct4 and Sox2) expression levels in MEF cells. Cordycepin, a major active component of Cordycepsmilitaris, also could up-regulate Oct4 and Sox2 gene expression. Furthermore, we used ES and iPS cells and treated them with different concentrations of Cordycepin (replaced LIF in the culture medium) to test whether it was useful to maintain the pluripotency. The results showed higher expression levels of several stem cells markers in 10 μM Cordycepin-treated ES and iPS cells compared to controls that did not contain LIF, including alkaline phosphatase, SSEA1, and Nanog. Embryonic body formation and differentiation confirmed that 10 μM Cordycepin-containing medium was capable to maintain stem cells pluripotency after four times passages. For mechanism analysis, microarray analysis indicated extracellular matrix and Jak/Stat signaling pathway as the top two deregulated pathways. In ECM pathway, we determined that the integrin αVβ5 expression levels and phosphorylated Src levels increased after Cordycepin treatment. In addition, the phosphorylated Jak2 and phosphorylated Sat3 protein levels were increased after Cordycepin treatment and suppressed with the Jak2 inhibitor, AG490. The expression of cytokines associated with Jak2/Stat3 signaling pathway were also up-regulated by Q-PCR and ELISA assay. Lastly, we used Oct4-GFP MEF cells to test iPS generation efficiency following Cordycepin treatment. We observed that 10 Μm Cordycepin significantly increased the iPS generation efficiency in day 21. In conclusion, we demonstrated Cordycepin could maintain the pluripotency of stem cells through both of ECM and Jak2/Stat3 signaling pathway and improved iPS generation efficiency.

Keywords: cordycepin, iPS cells, Jak2/Stat3 signaling pathway, molecular biology

Procedia PDF Downloads 400

Authors: Mei-Ling Chan, Jin-Ming Wu, Konstantin V. Kudryavtsev, Jih-Hwa Guh

Abstract:

Prostate cancer is one of the most common malignant disease in men. KUD983 is an enantiomerically pure β-dipeptide derivative, which may have anti-cancer effects. In the present study, KUD983 exhibits powerful activity against hormone-refractory prostate cancer (HRPC) PC-3 and DU145 cells. The IC50 values of KUD983 in PC-3 and DU145 cells are 0.56±0.07M and 0.50±0.04 M respectively. KUD983 induced G1 arrest of the cell cycle and subsequent apoptosis associated with the down-regulation of several related proteins including cyclin D1, cyclin E and Cdk4, and the de-phosphorylation of RB. The protein expressions of nuclear and total c-Myc protein, which was able to regulate the expression of both cyclin D1 and cyclin E, were significantly suppressed by KUD983. Phosphoinositide 3-kinase (PI3K)/Akt/mammalian target of rapamycin (mTOR) is an important signaling pathway that influences the energy metabolism, cell cycle, proliferation, survival and apoptosis of cells, and is associated with numerous other signaling pathways. The Western Blot data revealed that KUD983 inhibited PI3K/Akt and mTOR/p70S6K/4E-BP1 pathways. The transient transfection of constitutively active myristylated Akt (myr-Akt) cDNA significantly reversed KUD983-induced caspase activation but did not abolish the suppression of mTOR/p70S6K/4E-BP1 signaling cascade indicating the presence of both Akt-dependent and -independent pathways. Moreover, KUD983-induced effect was collaborated with the down-regulation of anti-apoptotic Bcl-2 members (e.g., Bcl-2, and Mcl-1) and IAP family members (e.g., survivin). Furthermore, KUD983 induced autophagic cell death using confocal microscopic examination, investigating the level of conversion of LC3-I to LC3-II and flow cytometric detection of AVO-positive cells. Taken together, the data suggest that KUD983 is an anticancer β-dipeptide against HRPCs through the inhibition of cell proliferation and induction of apoptotic and autophagic cell death. The suppression of signaling pathways mediated by c-Myc, PI3K/Akt and mTOR/p70S6K/4E-BP1 and the collaboration with down-regulation of Mcl-1 and survivin may indicate the mechanism of KUD983 against HRPC.

Keywords: β-dipeptide, hormone-refractory prostate cancer, mTOR, PI3K/Akt

Procedia PDF Downloads 252