61 research outputs found

    Analysis of Soil Nailed Walls Under Harmonic Dynamic Excitations Using Finite Difference Method

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    Soil nailing is an efficient method to stabilize different soil structures. The method has been extensively used for improving stability of slopes. The construction process of Soil nailed walls commonly involve three basic sections: excavation, nail installation and face stabilization. The nail bars are inserted into ground by either drilling or grouting and are usually arranged in both horizontal and vertical directions. Present research intends to understand Soil-nailed wall behavior under dynamic excitations. Employing finite difference method a three dimensional model has been developed in the proper finite difference code. Soil constitutive behavior for dynamic analyses is predicted taking into account soil hysteresis behavior. To simulate nail bars cable structural elements are employed and also liner structural elements will be utilized for shotcrete facing. Dynamic excitation incorporated as semi-seismic harmonic loading is applied at the bottom of the model where represents soil subgrade. The boundary conditions are considered to be antisymmetric during dynamic analyses. Effects of different crucial factors are monitored during investigations. Some parameters such as, input motion frequency, nail inclination, nail length as well as soil strength properties have been examined

    Seismic Response of Structures with Underground Stories Considering Non-Linear Soil-Structure Interaction

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    Most of the research conducted for soil-structure interaction analysis of structures are assuming the linear behavior of soil. It is well known that during strong ground excitations the soil adjacent to the structure behaves highly non-linear. The nonlinear soil behavior affects the soil-structure interaction in a complex way especially because of the inadequacy in modeling the unbounded soil medium. In the case where an elastic soil behavior is assumed, the surface motion will be amplified proportionally to the input motion. However, in reality the amplitude and frequency content of the response are modified due to the soil’s stiffness degradation and higher energy dissipation. The present work deals with the influence of soil non-linearity, introduced by hysteretic behavior of near-field soil, on the soil-foundation-structure interaction phenomena. The objective is to reveal the beneficial or detrimental effects of the non-linear SSI concerning both the drift and settlement of structures with underground stories. To examine the effect of non-linear soil-structure interaction a realistic non-linear soil model is incorporated into the finite difference FLAC software. To better understanding the non-linear dynamic SSI, interface elements are also used between the near-field soil and basement walls. For a practical structure throughout a parametric study, some non-linear seismic analyses are performed to demonstrate the effectiveness of the affecting parameters in response of the structure. The results showed much difference on seismic response of structure such as drift, settlement and developing pressure around the basement walls when the non-linear soil-structure interaction is considered

    Nonlinear Seismic Analysis of Buried Pipelines During Liquefaction

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    The safety of buried pipelines during earthquakes has involved a great deal of attention in last few years. Important characteristics of buried pipelines are that they cover large areas and can be subjected to a variety of geotectonic hazards. Earthquake damages to buried pipelines can be attributed to transient ground deformations (TGD), permanent ground deformations (PGD) or both. PGD occurs as a result of surface faulting, liquefaction, landslides, and differential settlement from consolidation of cohesionless soil. To evaluate seismic behavior of buried pipelines subjected to large values of permanent ground deformations, appropriate non-linear cyclic stress-strain relationship should be implemented in any numerical method. Among the phenomena, which cause permanent ground deformations, the settlement and lateral spreading induced by liquefaction are considered as the main cause of damage in buried structures. Therefore, this study is aimed to take into account the potential of liquefaction during an earthquake into the numerical analysis of buried pipelines using FEM. During the earthquake, the soil volume and also pore-pressure water is changed and therefore as saturated loose sands undergo simple shear deformations, the stiffness at any time is changed as the function of mean normal effective stress. In this study, a hypo-elastic model is adopted for the soil to evaluate changes in the pore pressures and also effective stresses during the excitation. In a finite element modeling, for the areas not expecting the liquefaction to occur, the pipe is modeled using beam elements and soil is modeled by some bi-linear springs; while for liquefied areas, the pipe is modeled by shell elements and solid elements are used to model the surrounding soil

    An Experimental-Intelligent Method to Predict Noise Value of Drilling in Dimension Stone Industry

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    The noise of drilling in the dimension stone business is unbearable for both the workplace and the people who work there. In order to reduce the negative effects drilling has on the health of the environment, the drilling noise has to be measured, assessed, and controlled. The main purpose of this work is to investigate an experimental-intelligent method to predict the noise value of drilling in the dimension stone industry. For this purpose, 135 laboratory tests are designed on five types of rocks (four types of hard rock and one type of soft rock): and their results are measured in the first step. In the second step, due to the unpredicted and uncertain issues in this case, artificial intelligence (AI) approaches are applied, and the modeling is conducted using three intelligent systems (IS): namely an adaptive neuro-fuzzy inference system-SCM (ANFIS-SCM): an adaptive neuro-fuzzy inference system-FCM (ANFIS-FCM): and the radial basis function network (RBF) neural network. 75% of the samples are considered for training, and the rest for testing. Several models are constructed, and the results indicate that although there is no significant difference between the models according to the performance indices, the proposed construction of ANFIS-SCM can be considered as an efficient tool in the evaluation of drilling noise. Finally, several scenarios are designed with different input modes, and the results obtained prove that the types of rock and the drill bits are more important than the operational characteristics of the machine

    MicroRNAs promote skeletal muscle differentiation of mesodermal iPSC-derived progenitors

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    Muscular dystrophies (MDs) are often characterized by impairment of both skeletal and cardiac muscle. Regenerative strategies for both compartments therefore constitute a therapeutic avenue. Mesodermal iPSC-derived progenitors (MiPs) can regenerate both striated muscle types simultaneously in mice. Importantly, MiP myogenic propensity is influenced by somatic lineage retention. However, it is still unknown whether human MiPs have in vivo potential. Furthermore, methods to enhance the intrinsic myogenic properties of MiPs are likely needed, given the scope and need to correct large amounts of muscle in the MDs. Here, we document that human MiPs can successfully engraft into the skeletal muscle and hearts of dystrophic mice. Utilizing non-invasive live imaging and selectively induced apoptosis, we report evidence of striated muscle regeneration in vivo in mice by human MiPs. Finally, combining RNA-seq and miRNA-seq data, we define miRNA cocktails that promote the myogenic potential of human MiPs

    Bone growth during rapamycin therapy in young rats

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    <p>Abstract</p> <p>Background</p> <p>Rapamycin is an effective immunosuppressant widely used to maintain the renal allograft in pediatric patients. Linear growth may be adversely affected in young children since rapamycin has potent anti-proliferative and anti-angiogenic properties.</p> <p>Methods</p> <p>Weanling three week old rats were given rapamycin at 2.5 mg/kg daily by gavage for 2 or 4 weeks and compared to a Control group given equivalent amount of saline. Morphometric measurements and biochemical determinations for serum calcium, phosphate, iPTH, urea nitrogen, creatinine and insulin-growth factor I (IGF-I) were obtained. Histomorphometric analysis of the growth plate cartilage, in-situ hybridization experiments and immunohistochemical studies for various proteins were performed to evaluate for chondrocyte proliferation, chondrocyte differentiation and chondro/osteoclastic resorption.</p> <p>Results</p> <p>At the end of the 2 weeks, body and tibia length measurements were shorter after rapamycin therapy associated with an enlargement of the hypertrophic zone in the growth plate cartilage. There was a decrease in chondrocyte proliferation assessed by <it>histone-4 </it>and <it>mammalian target of rapamycin </it>(<it>mTOR</it>) expression. A reduction in <it>parathyroid hormone/parathyroid hormone related peptide (PTH/PTHrP) </it>and an increase in <it>Indian hedgehog </it>(<it>Ihh</it>) expression may explain in part, the increase number of hypertrophic chondrocytes. The number of TRAP positive multinucleated chondro/osteoclasts declined in the chondro-osseous junction with a decrease in the <it>receptor activator of nuclear factor kappa β ligand </it>(<it>RANKL</it>) and <it>vascular endothelial growth factor </it>(<it>VEGF</it>) expression. Although body and tibial length remained short after 4 weeks of rapamycin, changes in the expression of chondrocyte proliferation, chondrocyte differentiation and chondro/osteoclastic resorption which were significant after 2 weeks of rapamycin improved at the end of 4 weeks.</p> <p>Conclusion</p> <p>When given to young rats, 2 weeks of rapamycin significantly decreased endochondral bone growth. No catch-up growth was demonstrated at the end of 4 weeks, although markers of chondrocyte proliferation and differentiation improved. Clinical studies need to be done to evaluate these changes in growing children.</p

    The proteasome inhibitor MG-132 sensitizes PC-3 prostate cancer cells to ionizing radiation by a DNA-PK-independent mechanism

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    BACKGROUND: By modulating the expression levels of specific signal transduction molecules, the 26S proteasome plays a central role in determining cell cycle progression or arrest and cell survival or death in response to stress stimuli, including ionizing radiation. Inhibition of proteasome function by specific drugs results in cell cycle arrest, apoptosis and radiosensitization of many cancer cell lines. This study investigates whether there is also a concomitant increase in cellular radiosensitivity if proteasome inhibition occurs only transiently before radiation. Further, since proteasome inhibition has been shown to activate caspase-3, which is involved in apoptosis, and caspase-3 can cleave DNA-PKcs, which is involved in DNA-double strand repair, the hypothesis was tested that caspase-3 activation was essential for both apoptosis and radiosensitization following proteasome inhibition. METHODS: Prostate carcinoma PC-3 cells were treated with the reversible proteasome inhibitor MG-132. Cell cycle distribution, apoptosis, caspase-3 activity, DNA-PKcs protein levels and DNA-PK activity were monitored. Radiosensitivity was assessed using a clonogenic assay. RESULTS: Inhibition of proteasome function caused cell cycle arrest and apoptosis but this did not involve early activation of caspase-3. Short-time inhibition of proteasome function also caused radiosensitization but this did not involve a decrease in DNA-PKcs protein levels or DNA-PK activity. CONCLUSION: We conclude that caspase-dependent cleavage of DNA-PKcs during apoptosis does not contribute to the radiosensitizing effects of MG-132

    Morphogenesis of the T4 tail and tail fibers

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    Remarkable progress has been made during the past ten years in elucidating the structure of the bacteriophage T4 tail by a combination of three-dimensional image reconstruction from electron micrographs and X-ray crystallography of the components. Partial and complete structures of nine out of twenty tail structural proteins have been determined by X-ray crystallography and have been fitted into the 3D-reconstituted structure of the "extended" tail. The 3D structure of the "contracted" tail was also determined and interpreted in terms of component proteins. Given the pseudo-atomic tail structures both before and after contraction, it is now possible to understand the gross conformational change of the baseplate in terms of the change in the relative positions of the subunit proteins. These studies have explained how the conformational change of the baseplate and contraction of the tail are related to the tail's host cell recognition and membrane penetration function. On the other hand, the baseplate assembly process has been recently reexamined in detail in a precise system involving recombinant proteins (unlike the earlier studies with phage mutants). These experiments showed that the sequential association of the subunits of the baseplate wedge is based on the induced-fit upon association of each subunit. It was also found that, upon association of gp53 (gene product 53), the penultimate subunit of the wedge, six of the wedge intermediates spontaneously associate to form a baseplate-like structure in the absence of the central hub. Structure determination of the rest of the subunits and intermediate complexes and the assembly of the hub still require further study

    PI3Kinase signaling in glioblastoma

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    Glioblastoma (GBM) is the most common primary tumor of the CNS in the adult. It is characterized by exponential growth and diffuse invasiveness. Among many different genetic alterations in GBM, e.g., mutations of PTEN, EGFR, p16/p19 and p53 and their impact on aberrant signaling have been thoroughly characterized. A major barrier to develop a common therapeutic strategy is founded on the fact that each tumor has its individual genetic fingerprint. Nonetheless, the PI3K pathway may represent a common therapeutic target to most GBM due to its central position in the signaling cascade affecting proliferation, apoptosis and migration. The read-out of blocking PI3K alone or in combination with other cancer pathways should mainly focus, besides the cytostatic effect, on cell death induction since sublethal damage may induce selection of more malignant clones. Targeting more than one pathway instead of a single agent approach may be more promising to kill GBM cells

    Idiopathic pulmonary fibrosis is strongly associated with productive infection by herpesvirus saimiri

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    Idiopathic pulmonary fibrosis is a fatal disease without effective therapy or diagnostic test. To investigate a potential role for c�herpesviruses in this disease, 21 paraffin-embedded lung biopsies from patients diagnosed with idiopathic pulmonary fibrosis and 21 lung biopsies from age-matched controls with pulmonary fibrosis of known etiology were examined for a series of c�herpesviruses’ DNA/RNA and related proteins using in situ hybridization and reverse transcriptase-polymerase chain reaction (RT-PCR)-based methods. We detected four proteins known to be in the genome of several c�herpesviruses (cyclin D, thymidylate synthase, dihydrofolate reductase, and interleukin-17) that were strongly co-expressed in the regenerating epithelial cells of each of the 21 idiopathic pulmonary fibrosis cases and not in the benign epithelia of the controls. Among the c� herpesviruses, only herpesvirus saimiri expresses all four of these ‘pirated’ mammalian proteins. We found herpesvirus saimiri DNA in the regenerating epithelial cells of 21/21 idiopathic pulmonary fibrosis cases using four separate probe sets but not in the 21 controls. RT-PCR showed that the source of the cyclin D RNA in active idiopathic pulmonary fibrosis was herpesvirus saimiri and not human. We cloned and sequenced part of genome corresponding to the DNA polymerase herpesvirus saimiri gene from an idiopathic pulmonary fibrosis sample and it matched 100% with the published viral sequence. These data are consistent with idiopathic pulmonary fibrosis representing herpesvirus saimiri-induced pulmonary fibrosis. Thus, treatment directed against viral proliferation and/or viral-associated proteins may halt disease progression. Further, demonstration of the viral nucleic acids or proteins may help diagnose the disease
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