718 research outputs found

    Analysis of a Frame-Shear Wall Concrete Structure by Using Base Isolation and Evaluation of Structure-Soil Interaction

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    A base isolation system is a type of earthquake-resistant structure design approach based on the principle of reducing a structure’s earthquake response rather than increasing the structure’s earthquake resistance capacity. Seismic base isolated structures have the ability to make large displacements relative to the level of insulation elements. This means that a large structure performs very small displacements between floors during an earthquake and exhibits a rigid body behavior. At this point, the earthquake forces acting on the structure decrease along with the floors. In this article a school building composed of frame-shear wall is resolved primarily with the traditional fixed base structure system, mode shapes are found and periods are obtained. For earthquake response analysis, earthquake loads are distributed to the floors using the equivalent seismic load method and structural elements experiencing capacity problems are found. Then, using the earthquake record, larger failure of cross sections and capacity problems are obtained compared to the first method. In the second stage, the same structure is dissolved again by placing the lead core rubber base isolators between the base and the vertical structural members. The periods of structures under earthquake load have increased significantly by utilizing base isolation, as a result of that spectral accelerations decreased. Thus, large decreases in the shear forces acting to the structure are determined and failures of cross sections are removed

    Glucose-6-phosphate dehydrogenase and transketolase modulate breast cancer cell metabolic reprogramming and correlate with poor patient outcome

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    The pentose phosphate pathway is a fundamental metabolic pathway that provides cells with ribose and NADPH required for anabolic reactions - synthesis of nucleotides and fatty acids - and maintenance of intracellular redox homeostasis. It plays a key role in tumor metabolic reprogramming and has been reported to be deregulated in different types of tumors. Herein, we silenced the most important enzymes of this pathway - glucose-6-phosphate dehydrogenase (G6PD) and transketolase (TKT) - in the human breast cancer cell line MCF7. We demonstrated that inhibition of G6PD, the oxidative branch-controlling enzyme, reduced proliferation, cell survival and increased oxidative stress. At the metabolic level, silencing of both enzymes reduced ribose synthesis. G6PD silencing in particular, augmented the glycolytic flux, reduced lipid synthesis and increased glutamine uptake, whereas silencing of TKT reduced the glycolytic flux. Importantly, we showed using breast cancer patient datasets that expression of both enzymes is positively correlated and that high expression levels of G6PD and TKT are associated with decreased overall and relapse-free survival. Altogether, our results suggest that this metabolic pathway could be subjected to therapeutic intervention to treat breast tumors and warrant further investigation

    CHANGES OF THYROID HORMONES IN DIFFERENT PHYSIOLOGICAL PERIODS IN WHITE GOATS

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    ABSTRACT The levels of thyroid hormones are important indicator of metabolic activity. The knowledge of the metabolic activity in different physiological periods, animals readjusted dietary regimen. Therefore, in this study, changes of triiodotironine (T3) and thyroxine (T4) hormones in the blood serum of female (n=14) and male (n=9) white goats were studied for a duration of one year through different physiological periods [breeding (September-October), gestation (November to March), postpartum-sucking (April-May) and milking (June to August)]. Results show that the differences in T3 and T4 hormone levels between sexes are statistically unimportant in breeding, gestation, postpartum-sucking and milking periods, while the changes for each sex between the physiological periods are important (p<0.05). Also, it has been found out that the thyroid hormone levels in different physiological periods are under the influence of the environmental temperature changes

    Dynamic phase transition properties and hysteretic behavior of a ferrimagnetic core-shell nanoparticle in the presence of a time dependent magnetic field

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    We have presented dynamic phase transition features and stationary-state behavior of a ferrimagnetic small nanoparticle system with a core-shell structure. By means of detailed Monte Carlo simulations, a complete picture of the phase diagrams and magnetization profiles have been presented and the conditions for the occurrence of a compensation point TcompT_{comp} in the system have been investigated. According to N\'{e}el nomenclature, the magnetization curves of the particle have been found to obey P-type, N-type and Q-type classification schemes under certain conditions. Much effort has been devoted to investigation of hysteretic response of the particle and we observed the existence of triple hysteresis loop behavior which originates from the existence of a weak ferromagnetic core coupling Jc/JshJ_{c}/J_{sh}, as well as a strong antiferromagnetic interface exchange interaction Jint/JshJ_{int}/J_{sh}. Most of the calculations have been performed for a particle in the presence of oscillating fields of very high frequencies and high amplitudes in comparison with exchange interactions which resembles a magnetic system under the influence of ultrafast switching fields. Particular attention has also been paid on the influence of the particle size on the thermal and magnetic properties, as well as magnetic features such as coercivity, remanence and compensation temperature of the particle. We have found that in the presence of ultrafast switching fields, the particle may exhibit a dynamic phase transition from paramagnetic to a dynamically ordered phase with increasing ferromagnetic shell thickness.Comment: 12 pages, 12 figure

    The spatial range of peripheral collinear facilitation

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    Contrast detection thresholds for a central Gabor patch (target) can be modulated by the presence of co-oriented and collinear high contrast Gabors flankers. In foveal vision collinear facilitation can be observed for target-to-flankers relative distances beyond two times the wavelength (λ) of the Gabor's carrier, while for shorter relative distances (<2λ) there is suppression. These modulatory influences seem to disappear after 12λ. In this study, we measured contrast detection thresholds for different spatial frequencies (1, 4 and 6 cpd) and target-to-flankers relative distances ranging from 6 to 16λ, but with collinear configurations presented in near periphery at 4° of eccentricity. Results showed that in near periphery collinear facilitation extends beyond 12λ for the higher spatial frequencies tested (4 and 6 cpd), while it decays already at 10λ for the lowest spatial frequency used (i.e., 1 cpd). In addition, we found that increasing the spatial frequency the peak of collinear facilitation shifts towards larger target-to-flankers relative distances (expressed as multiples of the stimulus wavelength), an effect never reported neither for near peripheral nor for central vision. The results suggest that the peak and the spatial extent of collinear facilitation in near periphery depend on the spatial frequency of the stimuli used

    Oxidative pentose phosphate pathway enzyme 6-phosphogluconate dehydrogenase plays a key role in breast cancer metabolism

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    The pentose phosphate pathway (PPP) plays an essential role in the metabolism of breast cancer cells for the management of oxidative stress and the synthesis of nucleotides. 6-phosphogluconate dehydrogenase (6PGD) is one of the key enzymes of the oxidative branch of PPP and is involved in nucleotide biosynthesis and redox maintenance status. Here, we aimed to analyze the functional importance of 6PGD in a breast cancer cell model. Inhibition of 6PGD in MCF7 reduced cell proliferation and showed a significant decrease in glucose consumption and an increase in glutamine consumption, resulting in an important alteration in the metabolism of these cells. No difference in reactive oxygen species (ROS) production levels was observed after 6PGD inhibition, indicating that 6PGD, in contrast to glucose 6-phosphate dehydrogenase, is not involved in redox balance. We found that 6PGD inhibition also altered the stem cell characteristics and mammosphere formation capabilities of MCF7 cells, opening new avenues to prevent cancer recurrance after surgery or chemotherapy. Moreover, inhibition of 6PGD via chemical inhibitor S3 resulted in an induction of senescence, which, together with the cell cycle arrest and apoptosis induction, might be orchestrated by p53 activation. Therefore, we postulate 6PGD as a novel therapeutic target to treat breast cancer

    Stationary State Solutions of a Bond Diluted Kinetic Ising Model: An Effective-Field Theory Analysis

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    We have examined the stationary state solutions of a bond diluted kinetic Ising model under a time dependent oscillating magnetic field within the effective-field theory (EFT) for a honeycomb lattice (q=3)(q=3). Time evolution of the system has been modeled with a formalism of master equation. The effects of the bond dilution, as well as the frequency (ω)(\omega) and amplitude (h/J)(h/J) of the external field on the dynamic phase diagrams have been discussed in detail. We have found that the system exhibits the first order phase transition with a dynamic tricritical point (DTCP) at low temperature and high amplitude regions, in contrast to the previously published results for the pure case \cite{Ling}. Bond dilution process on the kinetic Ising model gives rise to a number of interesting and unusual phenomena such as reentrant phenomena and has a tendency to destruct the first-order transitions and the DTCP. Moreover, we have investigated the variation of the bond percolation threshold as functions of the amplitude and frequency of the oscillating field.Comment: 8 pages, 4 figure

    Glyceraldehyde-3-phosphate dehydrogenase is overexpressed in colorectal cancer onset

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    Background Glyceraldehyde-3-phosphate dehydrogenase (GAPDH) is an essential regulator of glycolysis used as a housekeeping marker for gene/protein normalisation. Given the pivotal role of GAPDH in tumour metabolism, our aim was to correlate its protein expression with tumour staging and prognosis of colorectal cancer. Methods GAPDH expression was immunohistochemically analysed in tumour tissues from 62 colorectal cancer (CRC) patients, and validated at mRNA level in an independent dataset comprising 98 paired stage II CRC and normal samples. Staining quantification was performed by computational image analysis, and correlations between GAPDH expression and tumour progression stage were assessed. Gene expression profiling was performed using Affymetrix microarrays. Probability of patient survival and disease-free survival were analysed by the univariate product-limit method of Kaplan-Meier. Groups were compared using Kruskal-Wallis tests. Results Overexpression of GAPDH is positively associated with early stage tumours without regional lymph node and distant metastases involved. These results were reinforced by those obtained at mRNA level. Conclusion Studying the role of GAPDH in malignant transformation can shed new light on the understanding of tumour onset and lead to the design of more efficient personalised therapies

    The landscape of tiered regulation of breast cancer cell metabolism

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    Altered metabolism is a hallmark of cancer, but little is still known about its regulation. In this study, we measure transcriptomic, proteomic, phospho-proteomic and fluxomics data in a breast cancer cell-line (MCF7) across three different growth conditions. Integrating these multiomics data within a genome scale human metabolic model in combination with machine learning, we systematically chart the different layers of metabolic regulation in breast cancer cells, predicting which enzymes and pathways are regulated at which level. We distinguish between two types of reactions, directly and indirectly regulated. Directly-regulated reactions include those whose flux is regulated by transcriptomic alterations (~890) or via proteomic or phospho-proteomics alterations (~140) in the enzymes catalyzing them. We term the reactions that currently lack evidence for direct regulation as (putative) indirectly regulated (~930). Many metabolic pathways are predicted to be regulated at different levels, and those may change at different media conditions. Remarkably, we find that the flux of predicted indirectly regulated reactions is strongly coupled to the flux of the predicted directly regulated ones, uncovering a tiered hierarchical organization of breast cancer cell metabolism. Furthermore, the predicted indirectly regulated reactions are predominantly reversible. Taken together, this architecture may facilitate rapid and efficient metabolic reprogramming in response to the varying environmental conditions incurred by the tumor cells. The approach presented lays a conceptual and computational basis for mapping metabolic regulation in additional cancers
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