899 resultados para Load-cycle analysis


Relevância:

80.00% 80.00%

Publicador:

Resumo:

Intake of fruits rich in antioxidants in daily diet is suggested to be cancer preventive. Sapota is a tropical fruit grown and consumed extensively in several countries including India and Mexico. Here we show that methanolic extracts of Sapota fruit (MESF) induces cytotoxicity in a dose-dependent manner in cancer cell lines. Cell cycle analysis suggested activation of apoptosis, without arresting cell cycle progression. Annexin V-propidium iodide double-staining demonstrated that Sapota fruit extracts potentiate apoptosis rather than necrosis in cancer cells. Loss of mitochondrial membrane potential, upregulation of proapoptotic proteins, activation of MCL-1, PARP-1, and Caspase 9 suggest that MESF treatment leads to activation of mitochondrial pathway of apoptosis. More importantly, we show that MESF treatment leads to significant inhibition of tumor growth and a 3-fold increase in the life span of tumor bearing animals compared to untreated tumor mice.

Relevância:

80.00% 80.00%

Publicador:

Resumo:

Marine invertebrates called ascidians are prolific producers of bioactive substances. The ascidian Eudistoma viride, distributed along the Southeast coast of India, was investigated for its in vitro cytotoxic activity against human cervical carcinoma (HeLa) cells by the MTT assay. The crude methanolic extract of E. viride, with an IC50 of 53 mu g/ml, was dose-dependently cytotoxic. It was more potent at 100 mu g/ml than cyclohexamide (1 mu g/ml), reducing cell viability to 9.2%. Among nine fractions separated by chromatography, ECF-8 exhibited prominent cytoxic activity at 10 mu g/ml. The HPLC fraction EHF-21 of ECF-8 was remarkably dose- and time-dependently cytotoxic, with 39.8% viable cells at 1 mu g/ml compared to 51% in cyclohexamide-treated cells at the same concentration; the IC50 was 0.49,mu g/ml. Hoechst staining of HeLa cells treated with EHF-2I at 0.5 mu g/ml revealed apoptotic events such an cell shrinkage, membrane blebbing, chromatin condensation and formation of apoptotic bodies. Cell size and granularity study showed changes in light scatter, indicating the characteristic feature of cells dying by apoptosis. The cell-cycle analysis of HeLa cells treated with fraction EHF-21 at 1 mu g/ml showed the marked arrest of cells in G(0)/G(1), S and G(2)/M phases and an increase in the sub G(0)/G(1) population indicated an increase in the apoptotic cell population. The statistical analysis of the sub-G(1) region showed a dose-dependent induction of apoptosis. DNA fragmentation was also observed in HeLa cells treated with EHF-21. The active EHF-2I fraction, a brominated indole alkaloid Eudistomin H, led to apoptotic death of HeLa cells.

Relevância:

80.00% 80.00%

Publicador:

Resumo:

New N'-2-oxo-1,2-dihydro-3H-indol-3-ylidene]benzohydrazide derivatives were synthesized and evaluated for their cytotoxic properties against murine leukemia, L1210, human leukemia, REH and K562, human T-cell leukemia, CEM and human cervix carcinoma, HeLa cells. Among the tested compounds, the 3,4,5-trimethoxy-N'-5-methyl-2-oxo-1,2-dihydro-3H-indol-3-ylidene]ben zohydrazide derivative (5t) emerged as the most potent inhibitor against all the tumor cell lines evaluated. To investigate the mechanism of action, 5t was further studied by cell cycle analysis, mitochondrial membrane potential analysis, DNA fragmentation and Annexin V-FITC flow cytometric analysis, which suggested that 5t was able to induce apoptosis at submicromolar range.

Relevância:

80.00% 80.00%

Publicador:

Resumo:

Endophytic fungi isolated from Catharanthus roseus were screened for the production of vincristine and vinblastine. Twenty-two endophytic fungi isolated from various tissues of C. roseus were characterized taxonomically by sequence analysis of the internal transcribed spacer (ITS) region of rDNA and grouped into 10 genera: Alternaria, Aspergillus, Chaetomium, Colletotrichum, Dothideomycetes, Eutypella, Eutypa, Flavodon, Fusarium and Talaromyces. The antiproliferative activity of these fungi was assayed in HeLa cells using the MTT assay. The fungal isolates Eutypella sp-CrP14, obtained from stem tissues, and Talaromyces radicus-CrP20, obtained from leaf tissues, showed the strongest antiproliferative activity, with IC50 values of 13.5 mu g/ml and 20 mu g/ml, respectively. All 22 endophytic fungi were screened for the presence of the gene encoding tryptophan decarboxylase (TDC), the key enzyme in the terpenoid indole alkaloid biosynthetic pathway, though this gene could only be amplified from T. radicus-CrP20 (NCBI GenBank accession number KC920846). The production of vincristine and vinblastine by T. radicus-CrP20 was confirmed and optimized in nine different liquid media. Good yields of vincristine (670 mu g/l) in modified M2 medium and of vinblastine (70 mu g/l) in potato dextrose broth medium were obtained. The cytotoxic activity of partially purified fungal vincristine was evaluated in different human cancer cell lines, with HeLa cells showing maximum susceptibility. The apoptosis-inducing activity of vincristine derived from this fungus was established through cell cycle analysis, loss of mitochondrial membrane potential and DNA fragmentation patterns.

Relevância:

80.00% 80.00%

Publicador:

Resumo:

Congress established a legal imperative to restore the quality of our surface waters when it enacted the Clean Water Act in 1972. The act requires that existing uses of coastal waters such as swimming and shellfishing be protected and restored. Enforcement of this mandate is frequently measured in terms of the ability to swim and harvest shellfish in tidal creeks, rivers, sounds, bays, and ocean beaches. Public-health agencies carry out comprehensive water-quality sampling programs to check for bacteria contamination in coastal areas where swimming and shellfishing occur. Advisories that restrict swimming and shellfishing are issued when sampling indicates that bacteria concentrations exceed federal health standards. These actions place these coastal waters on the U.S. Environmental Protection Agencies’ (EPA) list of impaired waters, an action that triggers a federal mandate to prepare a Total Maximum Daily Load (TMDL) analysis that should result in management plans that will restore degraded waters to their designated uses. When coastal waters become polluted, most people think that improper sewage treatment is to blame. Water-quality studies conducted over the past several decades have shown that improper sewage treatment is a relatively minor source of this impairment. In states like North Carolina, it is estimated that about 80 percent of the pollution flowing into coastal waters is carried there by contaminated surface runoff. Studies show this runoff is the result of significant hydrologic modifications of the natural coastal landscape. There was virtually no surface runoff occurring when the coastal landscape was natural in places such as North Carolina. Most rainfall soaked into the ground, evaporated, or was used by vegetation. Surface runoff is largely an artificial condition that is created when land uses harden and drain the landscape surfaces. Roofs, parking lots, roads, fields, and even yards all result in dramatic changes in the natural hydrology of these coastal lands, and generate huge amounts of runoff that flow over the land’s surface into nearby waterways. (PDF contains 3 pages)

Relevância:

80.00% 80.00%

Publicador:

Resumo:

This dissertation primarily describes chemical-scale studies of G protein-coupled receptors and Cys-loop ligand-gated ion channels to better understand ligand binding interactions and the mechanism of channel activation using recently published crystal structures as a guide. These studies employ the use of unnatural amino acid mutagenesis and electrophysiology to measure subtle changes in receptor function.

In chapter 2, the role of a conserved aromatic microdomain predicted in the D3 dopamine receptor is probed in the closely related D2 and D4 dopamine receptors. This domain was found to act as a structural unit near the ligand binding site that is important for receptor function. The domain consists of several functionally important noncovalent interactions including hydrogen bond, aromatic-aromatic, and sulfur-π interactions that show strong couplings by mutant cycle analysis. We also assign an alternate interpretation for the linear fluorination plot observed at W6.48, a residue previously thought to participate in a cation-π interaction with dopamine.

Chapter 3 outlines attempts to incorporate chemically synthesized and in vitro acylated unnatural amino acids into mammalian cells. While our attempts were not successful, method optimizations and data for nonsense suppression with an in vivo acylated tRNA are included. This chapter is aimed to aid future researchers attempting unnatural amino acid mutagenesis in mammalian cells.

Chapter 4 identifies a cation-π interaction between glutamate and a tyrosine residue on loop C in the GluClβ receptor. Using the recently published crystal structure of the homologous GluClα receptor, other ligand-binding and protein-protein interactions are probed to determine the similarity between this invertebrate receptor and other more distantly related vertebrate Cys-loop receptors. We find that many of the interactions previously observed are conserved in the GluCl receptors, however care must be taken when extrapolating structural data.

Chapter 5 examines inherent properties of the GluClα receptor that are responsible for the observed glutamate insensitivity of the receptor. Chimera synthesis and mutagenesis reveal the C-terminal portion of the M4 helix and the C-terminus as contributing to formation of the decoupled state, where ligand binding is incapable of triggering channel gating. Receptor mutagenesis was unable to identify single residue mismatches or impaired protein-protein interactions within this domain. We conclude that M4 helix structure and/or membrane dynamics are likely the cause of ligand insensitivity in this receptor and that the M4 helix has an role important in the activation process.

Relevância:

80.00% 80.00%

Publicador:

Resumo:

Tem sido descrito que o acúmulo de mutações em proto-oncogenes e genes supressores de tumor contribui para o direcionamento da célula à carcinogênese. Na maioria dos casos de câncer, as células apresentam proliferação descontrolada devido a alterações na expressão e/ou mutações de ciclinas, quinases dependentes de ciclinas e/ou inibidores do ciclo celular. Os tumores sólidos figuram entre o tipo de câncer mais incidente no mundo, sendo a quimioterapia e/ou hormônio-terapia, radioterapia e cirurgia os tratamentos mais indicados para estes tipos de tumores. Entretanto, o tratamento quimioterápico apresenta diversos efeitos colaterais e muitas vezes é ineficaz. Portanto, a busca por novas moléculas capazes de conter a proliferação destas células e com baixa toxicidade para o organismo se faz necessário. Este trabalho teve por objetivo avaliar a ação antitumoral in vitro de um novo composto sintético, a pterocarpanoquinona LQB118, sobre algumas linhagens tumorais humanas de alta prevalência e estudar alguns dos seus mecanismos de ação. As linhagens tumorais estudadas neste trabalho foram os adenocarcinomas de mama (MCF7) e próstata (PC-3), e carcinoma de pulmão (A549). A citotoxicidade foi avaliada pelo ensaio do MTT e a proliferação celular pela contagem de células vivas (exclusão do corante azul de tripan) e análise do ciclo celular (citometria de fluxo). A expressão gênica foi avaliada por RT-PCR e a apoptose foi avaliada por condensação da cromatina (microscopia de fluorescência-DAPI), fragmentação de DNA (eletroforese) e marcação com anexina V (citometria de fluxo). Das linhagens tumorais testadas, a de próstata (PC3) foi a que se mostrou mais sensível ao LQB 118, e em função deste resultado, os demais experimentos foram realizados com esta linhagem tumoral. O efeito citotóxico do LQB 118 se mostrou tempo e concentração dependente. Esta substância inibiu a proliferação celular e prejudicou a progressão do ciclo celular, acumulando células nas fases S e G2/M. Buscando esclarecer os mecanismos desta ação antitumoral, demonstrou-se que o LQB 118 inibe a expressão do mRNA do fator de transcrição c-Myc e das ciclinas D1 e B1, e induz a apoptose de tais células tumorais. Em suma, o LQB 118 é capaz de inibir a proliferação das células tumorais de próstata, alterando a expressão do mRNA de alguns genes reguladores do ciclo celular, resultando em interrupção do ciclo celular e indução de apoptose, indicando este composto como um potencial candidato a futuro medicamento no tratamento do câncer de próstata.

Relevância:

80.00% 80.00%

Publicador:

Resumo:

Nuclear RNA and DNA in muscle cell nuclei of laboratory-reared larvae of Walleye Pollock (Gadus chalcogrammus) were simultaneously measured through the use of flow cytometry for cell-cycle analysis during 2009–11. The addition of nuclear RNA as a covariate increased by 4% the classification accuracy of a discriminant analysis model that used cell-cycle, temperature, and standard length to measure larval condition, compared with a model without it. The greatest improvement, a 7% increase in accuracy, was observed for small larvae (<6.00 mm). Nuclear RNA content varied with rearing temperature, increasing as temperature decreased. There was a loss of DNA when larvae were frozen and thawed because the percentage of cells in the DNA synthesis cell-cycle phase decreased, but DNA content was stable during storage of frozen tissue.

Relevância:

80.00% 80.00%

Publicador:

Resumo:

Numerous piles are often subjected to the combination of cyclic axial and cyclic lateral loads in service, such as piled foundations for offshore platforms which may suffer swaying and rocking motions owing to wind and wave actions. In this research, centrifuge tests were conducted to investigate the effect of previous cyclic axial loads on the performance of pile groups subjected to subsequent cyclic lateral loads. Different pile installation methods were also applied to study the different behaviour of bored and jacked pile groups subjected to cyclic loads. During lateral load cycling, it is seen that cyclic axial loads to which pile groups were previously subjected could reduce the pile cap permanent lateral displacement in the first lateral load cycle but do not influence the incremental rate of permanent displacement in the following lateral load cycles. Moreover, it is found that previous cyclic axial loads could improve the pile cap cyclic lateral secant stiffness, especially for the pre-jacked pile group. When rocking motions were induced by cyclic lateral loads, pile groups subjected to cyclic axial loads before have smaller permanent settlement than those without the cyclic axial loading effect. The designers of piles that are intended to resist significant lateral loads without excessive deformations in service may wish to deploy cyclic axial preloading, accordingly.

Relevância:

80.00% 80.00%

Publicador:

Resumo:

As operational impacts from buildings are reduced, embodied impacts are increasing. However, the latter are seldom calculated in the UK; when they are, they tend to be calculated after the building has been constructed, or are underestimated by considering only the initial materials stage. In 2010, the UK Government recommended that a standard methodology for calculating embodied impacts of buildings be developed for early stage design decisions. This was followed in 2011-12 by the publication of the European TC350 standards defining the 'cradle to grave' impact of buildings and products through a process Life Cycle Analysis. This paper describes a new whole life embodied carbon and energy of buildings (ECEB) tool, designed as a usable empirical-based approach for early stage design decisions for UK buildings. The tool complies where possible with the TC350 standards. Initial results for a simple masonry construction dwelling are given in terms of the percentage contribution of each life cycle stage. The main difficulty in obtaining these results is found to be the lack of data, and the paper suggests that the construction and manufacturing industries now have a responsibility to develop new data in order to support this task. © 2013 The Authors. Published by Elsevier B.V. All rights reserved.

Relevância:

80.00% 80.00%

Publicador:

Resumo:

Coupled Monte Carlo depletion systems provide a versatile and an accurate tool for analyzing advanced thermal and fast reactor designs for a variety of fuel compositions and geometries. The main drawback of Monte Carlo-based systems is a long calculation time imposing significant restrictions on the complexity and amount of design-oriented calculations. This paper presents an alternative approach to interfacing the Monte Carlo and depletion modules aimed at addressing this problem. The main idea is to calculate the one-group cross sections for all relevant isotopes required by the depletion module in a separate module external to Monte Carlo calculations. Thus, the Monte Carlo module will produce the criticality and neutron spectrum only, without tallying of the individual isotope reaction rates. The onegroup cross section for all isotopes will be generated in a separate module by collapsing a universal multigroup (MG) cross-section library using the Monte Carlo calculated flux. Here, the term "universal" means that a single MG cross-section set will be applicable for all reactor systems and is independent of reactor characteristics such as a neutron spectrum; fuel composition; and fuel cell, assembly, and core geometries. This approach was originally proposed by Haeck et al. and implemented in the ALEPH code. Implementation of the proposed approach to Monte Carlo burnup interfacing was carried out through the BGCORE system. One-group cross sections generated by the BGCORE system were compared with those tallied directly by the MCNP code. Analysis of this comparison was carried out and led to the conclusion that in order to achieve the accuracy required for a reliable core and fuel cycle analysis, accounting for the background cross section (σ0) in the unresolved resonance energy region is essential. An extension of the one-group cross-section generation model was implemented and tested by tabulating and interpolating by a simplified σ0 model. A significant improvement of the one-group cross-section accuracy was demonstrated.

Relevância:

80.00% 80.00%

Publicador:

Resumo:

Thymidylate synthase (TS), an essential enzyme in DNA synthesis and repair, plays a key role in the events of cell cycle regulation and tumor formation. Here, an investigation was presented about subcellular location and biological function of viral TS from lymphocystis disease virus from China (LCDV-C) in fish cells. Fluorescence microscopy revealed that LCDV-C TS was predominantly localized in the cytoplasm in fish cells. Cell cycle analysis demonstrated that LCDV-C TS promoted cell cycle progression into S and G2/M phase in the constitutive expressed cells. As a result, the cells have a faster growth rate compared with the control cells as revealed by cell growth curves. For foci assay, the TS-expressed cells gave rise to foci 4-5 weeks after incubation. Microscopic examination of the TS-induced foci revealed multilayered growth and crisscross morphology characteristic of transformed cells. Moreover, LCDV-C TS predisposed the transfected cells to acquire an anchorage-independent phenotype and could grow in 0.3% soft agar. So the data reveal LCDV-C TS is sufficient to induce a transformed phenotype in fish cells in vitro and exhibits its potential ability in cell transformation. To our knowledge, it is the first report on viral TS sequences associated with transforming activity. (C) 2007 Elsevier Inc. All rights reserved.

Relevância:

80.00% 80.00%

Publicador:

Resumo:

In research field of oil geophysical prospecting, reservoir prediction is refers to forecasting physical properties of petroleum reservoir by using data of seismic and well logging, it is a research which can guide oil field development. Singularities of seismic and logging data are caused by the heterogeneity of reservoir physical property. It's one of important methods that using singularity characteristics of seismic and logging data to study the reservoir physical property in recently. Among them, realization of reservoir quantitative prediction by analyzing singularity of the data and enhancing transition description of data is difficulty in method research. Based on wavelet transform and the fractal theory, the paper studied the singularity judgment criterion for seismic and logging data, not only analyzed quantitative relation between singularity data and reservoir physical property, but also applied it in practical reservoir prediction. The main achievements are: 1. A new method which provides singular points and their strength information estimation at only one single scale is proposed by Herrmann (1999). Based on that, the dissertation proposed modified algorithm which realized singularity polarity detection. 2. The dissertation introduced onset function to generalize the traditional geologic boundaries variations model which used singularity characteristics to represent the abruptness of the lithologic velocity transition. We show that singularity analysis reveals generic singularity information conducted from velocity or acoustic impedance to seismogram based on the convolution seismic-model theory. Theory and applications indicated that singularity information calculated from seismic data was a natural attribute for delineating stratigraphy boundaries due to its excellent ability in detecting detailed geologic features. We demonstrated that singularity analysis was a powerful tool to delineate stratigraphy boundaries and inverse acoustic impedance and velocity. 3. The geologic significances of logging data singularity information were also presented. According to our analysis, the positions of singularities indicate the sequence stratigraphic boundary, and there is subtle relationship between the singularity strength and sedimentary environment, meanwhile the singularity polarity used to recognize stratigraphic base-level cycle. Based on all those above, a new method which provided sedimentary cycle analysis based on the singularity information of logging data in multiple scales was proposed in this dissertation. This method provided a quantitative tool for judging interface of stratum sequence and achieved good results in the actual application.

Relevância:

80.00% 80.00%

Publicador:

Resumo:

A continuous long (224m) and high-resolution core TY2 was recovered from paleo-maar-lake Tianyang, tropical South China. Based on the diatom records of the upper 130-m core, this paper focuses on exploring climate change and the lake evolution history in tropical South China during the past 240ka. The most typical and unique characteristics of the diatom assemblages is that, Aulacoseira granulata was dominant or absolutely dominant species (80-90%) during most parts of the 130-m core, while Cyclotella stelligera var. tenuis and Fragilaria construens var. venter were subdominant species in only limited parts of the lower and upper core, respectively. Time scale is always the biggest problem for the study of TY2 core, so although diatom is seldom used for establishing time scale, here we attempt this by correlating the diatom-reconstructed temperature sequence with the time scale of ODP core 806B from Equatorial Western Pacific. Verified by the few most reliable ages from TY2 core and the parallel core TYl, a rather reasonable and reliable time scale was established. 01S 7/6 falls at the depth of 100m (ca. 194kaBP), OIS 6/5 at 75m (ca. 132kaBP), OIS 5/4 at 46m (ca. 75kaBP), OIS 4-3 at 35m (ca. 60kaBP). Qualitative and quantitative environmental reconstructions are made on the basis of diatom assemblage ecotype and EDDI dataset. Correlation of diatom-reconstructed temperature and moisture changes of Core TY2 with pollen-reconstructed temperature and rainfall sequence of Core TYl proves that the results are quite consistent in most periods. Thus the reconstruction results from diatom are quite reliable, and probably have a much higher resolution than pollen results. Combined with lithological and magnetic susceptibility variations, the diatom analysis reveals that, the general climate in tropical South China during the past 240ka was warm and wet. On the time scale of glacial-interglacial, warm and wet, cool and dry are not always synchronous. It was relatively warm-wet during the penultimate interglacial, cool-dry during the penultimate glacial, warm-dry during the last interglacial, and cooler-drier during the last glacial. In contrast, on the time scale of subglacial-subinterglacial scales, warm and dry, cool and wet corresponds very obviously, showing very clear 21-23 ka precession cycle. Analysis also shows that, the water of Tianyang paleo-maar-lake was generally warm, turbulent, turbid, meso-trophic, slightly alkaline, low conductivity and fresh during the past 240 kaBP, with small variations in some parts. Tianyang paleolake experienced shallow to semi-deep lake in OIS7d, open shallow lake in OIS7c-OIS5b, shallow coastal lake in OIS5a-OIS4c, swamp in OIS4b, and then completely dried up in OIS3c. The lake evolution was mainly controlled by temperature and precipitation changes in tropical China. While temperature and precipitation changes were probably controlled by the migrations of monsoon rainband and the evaporation rate, which was in turn controlled by the evolution of East Asian monsoon. Therefore, when the summer monsoon was strongest the climate was warm-dry, when stronger the climate was warm-wet; when the winter monsoon was strongest the climate was cool-dry, stronger cool-wet. This mechanism caused the warm-dry sub interglacial and cool-wet subglacial climate in the tropical South China.

Relevância:

80.00% 80.00%

Publicador:

Resumo:

El objetivo de este trabajo consiste en estudiar la evolución de los destinos turísticos litorales consolidados a partir del análisis comparado entre Balneario Camboriú y Benidorm. Se trata de dos destinos localizados en contextos territoriales y turísticos diferentes, en los que se contrastan de manera empírica los indicadores de evolución de los destinos y se vinculan las dinámicas evolutivas con el modelo territorial-turístico resultante en cada destino. El análisis realizado permite contrastar los postulados de los modelos evolutivos clásicos (Butler, 1980) e incorporar los nuevos planteamientos de la geografía económica evolutiva. La investigación delimita cronológicamente los periodos de desarrollo de ambos destinos para identificar los factores con mayor incidencia en la evolución de los mismos. Una evolución marcada, fundamentalmente, por la ubicación geográfica, la planificación y gestión urbanoturística a diferentes escalas, la dependencia de determinados mercados emisores y la influencia de factores macroeconómicos. Un conjunto de factores interrelacionados que dibujan trayectorias dispares para los destinos analizados.