903 resultados para Ductile-to-brittle transition


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Infrastructure management agencies are facing multiple challenges, including aging infrastructure, reduction in capacity of existing infrastructure, and availability of limited funds. Therefore, decision makers are required to think innovatively and develop inventive ways of using available funds. Maintenance investment decisions are generally made based on physical condition only. It is important to understand that spending money on public infrastructure is synonymous with spending money on people themselves. This also requires consideration of decision parameters, in addition to physical condition, such as strategic importance, socioeconomic contribution and infrastructure utilization. Consideration of multiple decision parameters for infrastructure maintenance investments can be beneficial in case of limited funding. Given this motivation, this dissertation presents a prototype decision support framework to evaluate trade-off, among competing infrastructures, that are candidates for infrastructure maintenance, repair and rehabilitation investments. Decision parameters' performances measured through various factors are combined to determine the integrated state of an infrastructure using Multi-Attribute Utility Theory (MAUT). The integrated state, cost and benefit estimates of probable maintenance actions are utilized alongside expert opinion to develop transition probability and reward matrices for each probable maintenance action for a particular candidate infrastructure. These matrices are then used as an input to the Markov Decision Process (MDP) for the finite-stage dynamic programming model to perform project (candidate)-level analysis to determine optimized maintenance strategies based on reward maximization. The outcomes of project (candidate)-level analysis are then utilized to perform network-level analysis taking the portfolio management approach to determine a suitable portfolio under budgetary constraints. The major decision support outcomes of the prototype framework include performance trend curves, decision logic maps, and a network-level maintenance investment plan for the upcoming years. The framework has been implemented with a set of bridges considered as a network with the assistance of the Pima County DOT, AZ. It is expected that the concept of this prototype framework can help infrastructure management agencies better manage their available funds for maintenance.

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Increases in the production rate of cosmogenic radionuclides associated with geomagnetic excursions have been used as global tie-points for correlation between records of past climate from marine and terrestrial archives. We have investigated the relative timing of variations in 10Be production rate and the corresponding palaeomagnetic signal during one of the largest Pleistocene excursions, the Iceland Basin (IB) event (ca. 190 kyr), as recorded in two marine sediment cores (ODP Sites 1063 and 983) with high sedimentation rates. Variations in 10Be production rate during the excursion were estimated by use of 230Thxs normalized 10Be deposition rates and authigenic 10Be/9Be. Resulting 10Be production rates are compared with high-resolution records of geomagnetic field behaviour acquired from the same discrete samples. We find no evidence for a significant lock-in depth of the palaeomagnetic signal in these high sedimentation-rate cores. Apparent lock-in depths in other cores may sometimes be the result of lower sample resolution. Our results also indicate that the period of increased 10Be production during the IB excursion lasted longer and, most likely, started earlier than the corresponding palaeomagnetic anomaly, in accordance with previous observations that polarity transitions occur after periods of reduced geomagnetic field intensity prior to the transition. The lack of evidence in this study for a significant palaeomagnetic lock-in depth suggests that there is no systematic offset between the 10Be signal and palaeomagnetic anomalies associated with excursions and reversals, with significance for the global correlation of climate records from different archives.

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Due to demographic transition process, the educational public sector politics formers encounter a highly specific demographic situation because, nowadays, despite the demographic transition, population is still growing because of the demographic inertia; however, due to steady decline in fertility, young population tends to decrease in next years. In this way, aiming to make high school widely accessible in the country, the issue of education quality is highlighted as well the importance of the physical structure of schools and their teaching equipments to confirm a favorable or not environment for developing educational processes. In this way, this work aims to relate the enrollment of students as school types with the demand of young people who will be able to attend high school on the Rio Grande do Norte state by the year of 2020, emphasizing teaching unities structural aspects, from a school profiling to the design of three prospective alternatives. So, from INEP's Scholar Census data and IBGE population's projections, this work is composed by four stages: i) literature review about research related subjects; ii) database design and build; iii) school profiling; and, iv) prospective alternatives creation. As results, three alternatives relate potential demand and enrollment using the built profiles and they are: i) “Alternative A” attends PEE's requirements related to demands but do not provide improvements in the school structural aspects; ii) “Alternative B” points into an increase of enrollment offering to the detriment of school's structural conditions which are offered to these students; iii) “Alternative C” propitiates a quantitative enrollment increasing combined with improvements on school's physical structure. These alternatives help to support decision making related to goals and realization of universal access with physical conditions which are necessary to a favorable environment to educational activity development.

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We describe the labour market turnovers of young people using a household survey data collected from Cape Town industrial area. We measure the correlates of first unemployment duration out of school and find that matriculation and late cohort (leaving school after 2007) are related with reduced initial unemployment, yet matriculation impacts are reduced among late cohort relative to early cohort. Our estimation reveals that initial unemployment is not related with subsequent employment duration nor wage rates, but related with number of turnovers which suggests that a shorter spell is associated with more stable job tenure.

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The ABL family of non-receptor tyrosine kinases, ABL1 (also known as c-ABL) and ABL2 (also known as Arg), links diverse extracellular stimuli to signaling pathways that control cell growth, survival, adhesion, migration and invasion. ABL tyrosine kinases play an oncogenic role in human leukemias. However, the role of ABL kinases in solid tumors including breast cancer progression and metastasis is just emerging.

To evaluate whether ABL family kinases are involved in breast cancer development and metastasis, we first analyzed genomic data from large-scale screen of breast cancer patients. We found that ABL kinases are up-regulated in invasive breast cancer patients and high expression of ABL kinases correlates with poor prognosis and early metastasis. Using xenograft mouse models combined with genetic and pharmacological approaches, we demonstrated that ABL kinases are required for regulating breast cancer progression and metastasis to the bone. Using next generation sequencing and bioinformatics analysis, we uncovered a critical role for ABL kinases in promoting multiple oncogenic pathways including TAZ and STAT5 signaling networks and the epithelial to mesenchymal transition (EMT). These findings revealed a role for ABL kinases in regulating breast cancer tumorigenesis and bone metastasis and provide a rationale for targeting breast tumors with ABL-specific inhibitors.

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Aberrant regulation of the Wnt signalling pathway is a recurrent theme in cancer biology. Hyper activation due to oncogenic mutations and paracrine activity has been found in both colon cancer and breast cancer, and continues to evolve as a central mechanism in oncogenesis. PDLIM2, a cytoskeletal PDZ protein, is an IGF-1 regulated gene that is highly expressed in cancer cell lines derived from metastatic tumours. Suppression of PDLIM2 inhibits polarized cell migration, reverses the Epithelial to Mesenchymal transition (EMT) phenotype, suppresses the transcription of β-catenin target genes, and regulates gene expression of key transcription factors in EMT. This thesis investigates the mechanism by which PDLIM2 contributes to the maintenance of Wnt signalling in cancer cells. Here we show that PDLIM2 is a critical regulator of the Wnt pathway by regulating β-catenin at the adherens juctions, as also its transcriptional activity by the interaction of PDLIM2 with TCF4 at the nucleus. Evaluation of PDLIM2 in macrophages and co-culture studies with cancer cells and fibroblasts showed the influence exerted on PDLIM2 by paracrine cues. Thus, PDLIM2 integrates cytoskeleton signalling with gene expression by modulating the Wnt signalling pathway and reconciling microenvironmental cues with signals in epithelial cells. Negative correlation of mRNA and protein levels in the triple negative breast cancer cell BT549 suggests that PDLIM2 is part of a more complex mechanism that involves transcription and posttranslational modifications. GST pulldown studies and subsequent mass spectrometry analysis showed that PDLIM2 interacts with 300 proteins, with a high biological function in protein biosynthesis and Ubiquitin/proteasome pathways, including 13 E3 ligases. Overall, these data suggest that PDLIM2 has two distinct functions depending of its location. Located at the cytoplasm mediates cytoskeletal re-arrangements, whereas at the nucleus PDLIM2 acts as a signal transduction adaptor protein mediating transcription and ubiquitination of key transcription factors in cancer development.

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Proxy records from two piston cores in the Gulf of Mexico (GOM) provide a detailed (50-100 year resolution) record of climate variability over the last 14,000 years. Long-term (millennial-scale) trends and changes are related to the transition from glacial to interglacial conditions and movement of the average position of the Intertropical Convergence Zone (ITCZ) related to orbital forcing. The d18O of the surface-dwelling planktic foraminifer Globigerinoides ruber show negative excursions between 14 and 10.2 ka (radiocarbon years) that reflect influx of meltwater into the western GOM during melting of the Laurentide Ice Sheet. The relative abundance of the planktic foraminifer Globigerinoides sacculifer is related to transport of Caribbean water into the GOM. Maximum transport of Caribbean surface waters and moisture into the GOM associated with a northward migration of the average position of the ITCZ occurs between about 6.5 and 4.5 ka. In addition, abundance variations of G. sacculifer show century-scale variability throughout most of the Holocene. The GOM record is consistent with records from other areas, suggesting that century-scale variability is a pervasive feature of Holocene climate. The frequency of several cycles in the climate records is similar to cycles identified in proxy records of solar variability, indicating that at least some of the century-scale climate variability during the Holocene is due to external (solar) forcing.

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During the cleaning of the HPC core surfaces from Hole 480 for photography, the material removed was conserved carefully in approximately 10 cm intervals (by K. Kelts); this material was made available to us in the hope that it would be possible to obtain oxygen isotope stratigraphy for the site. The samples were, of course, somewhat variable in size, but the majority were probably between 5 and 10 cm**3. Had this been a normal marine environment, such sample sizes would have contained abundant planktonic foraminifers together with a small number of benthics. However, this is clearly not the case, for many samples contained no foraminifers, whereas others contained more benthics than planktonics. Among the planktonic foraminifers the commonest species are Globigerina bulloides, Neogloboquadrina dutertrei, and N. pachyderma. A few samples contain a more normal fauna with Globigerinoides spp. and occasional Globorotalia spp. Sample 480-3-3, 20-30 cm contained Globigerina rubescens, isolated specimens of which were noted in a few other samples in Cores 3,4, and 5. This is a particularly solution-sensitive species; in the open Pacific it is only found widely distributed at horizons of exceptionally low carbonate dissolution, such as. the last glacial-to-interglacial transition.

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The distribution of redox-sensitive metals in sediments is potentially a proxy for past ocean ventilation and productivity, but deconvolving these two major controls has proved difficult to date. Here we present a 740 kyr long record of trace element concentrations from an archived sediment core collected at ~15°S on the western flank of the East Pacific Rise (EPR) on 1.1 Myr old crust and underlying the largest known hydrothermal plume in the world ocean. The downcore trace element distribution is controlled by a variable diagenetic overprint of the inferred primary hydrothermal plume input. Two main diagenetic processes are operating at this site: redox cycling of transition metals and ferrihydrite to goethite transition during aging. The depth of oxidation in these sediments is controlled by fluctuations in the relative balance of bottom water oxygen and electron donor input (organic matter and hydrothermal sulfides). These fluctuations induce apparent variations in the accumulation of redox-sensitive species with time. Subsurface U and P peaks in glacial age sediments, in this and other published data sets along the southern EPR, indicate that basin-wide changes in deep ocean ventilation, in particular at glacial-interglacial terminations II, III, IV, and V, alter the depth of the oxidation front in the sediments. These basin-wide changes in the deep Pacific have significant implications for carbon partitioning in the ocean-atmosphere system, and the distribution of redox-sensitive metals in ridge crest sediment can be used to reconstruct past ocean conditions at abyssal depths in the absence of alternative proxy records.

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The Indian monsoon system is an important climate feature of the northern Indian Ocean. Small variations of the wind and precipitation patterns have fundamental influence on the societal, agricultural, and economic development of India and its neighboring countries. To understand current trends, sensitivity to forcing, or natural variation, records beyond the instrumental period are needed. However, high-resolution archives of past winter monsoon variability are scarce. One potential archive of such records are marine sediments deposited on the continental slope in the NE Arabian Sea, an area where present-day conditions are dominated by the winter monsoon. In this region, winter monsoon conditions lead to distinctive changes in surface water properties, affecting marine plankton communities that are deposited in the sediment. Using planktic foraminifera as a sensitive and well-preserved plankton group, we first characterize the response of their species distribution on environmental gradients from a dataset of surface sediment samples in the tropical and sub-tropical Indian Ocean. Transfer functions for quantitative paleoenvironmental reconstructions were applied to a decadal-scale record of assemblage counts from the Pakistan Margin spanning the last 2000?years. The reconstructed temperature record reveals an intensification of winter monsoon intensity near the year 100 CE. Prior to this transition, winter temperatures were >1.5°C warmer than today. Conditions similar to the present seem to have established after 450 CE, interrupted by a singular event near 950 CE with warmer temperatures and accordingly weak winter monsoon. Frequency analysis revealed significant 75-, 40-, and 37-year cycles, which are known from decadal- to centennial-scale resolution records of Indian summer monsoon variability and interpreted as solar irradiance forcing. Our first independent record of Indian winter monsoon activity confirms that winter and summer monsoons were modulated on the same frequency bands and thus indicates that both monsoon systems are likely controlled by the same driving force.

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Marine sediments from the Vøring Plateau (Norwegian Sea) have been studied for their dinoflagellate cyst (dinocyst) and foraminiferal content in order to reconstruct sea-surface conditions in the eastern Norwegian Sea during Marine Isotope Stage (MIS) 5e. In combination with stable oxygen isotope and ice rafted detritus (IRD) data, the variations in foraminiferal and dinocyst assemblage composition reflect a stepwise transition from the final phase of deglaciation (Termination II) into typical interglacial conditions. This stepwise change is repeated subsequently during the cooling conditions of glacial inception towards MIS 5d. The interval studied is characterized by relatively high abundances of Bitectatodinium tepikiense, in comparison to present-day values in the area, indicating a larger seasonal temperature amplitude with enhanced surface water stratification during MIS 5e. The important occurrence of the warm-temperate dinocyst Spiniferites mirabilis s.l. concurrent with subpolar foraminifers Turborotalita quinqueloba, Globigerina bulloides, and Globigerinita glutinata reveals that most pronounced interglacial marine conditions prevailed in the area just prior to the transition towards MIS 5d. The late stratigraphic position of this phase in the interglacial is verified by comparison with dinocyst data from south of Iceland, manifesting its over-regional implication. Besides the good agreement in dinocyst and foraminiferal assemblage changes, the variations in and between both fossil assemblages also point to the existence of some significant surface water variability in the eastern Norwegian Sea during MIS 5e.

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Chironomid headcapsules were used to reconstruct late glacial and early-Holocene summer temperatures at Lago Piccolo di Avigliana (LPA). Two training sets (northern Sweden, North America) were used to infer temperatures. The reconstructed patterns of temperature change agreed well with the GRIP and NGRIP d18O records. Inferred temperatures were high during the Bølling (ca 19 °C), slowly decreased to ca 17.5 °C during the Allerød, reached lowest temperatures (ca 16 °C) during the Younger Dryas, and increased to ca. 18.5 °C during the Preboreal. The amplitudes of change at climate transitions (i.e. Oldest Dryas/Bølling: 3 °C, Allerød/Younger Dryas: 1.5 °C, and Younger Dryas/Preboreal: 2.5 °C) were smaller than in the northern Alps but similar to those recorded at another site in northeastern Italy. Our results suggest that (1) Allerød temperatures were higher in the southern Alps and (2) higher during the Preboreal (1 °C) than during the Allerød. These differences might provide an explanation for the different responses of terrestrial-vegetation to late glacial and early-Holocene climatic changes in the two regions. Other sites on both sides of the Alps should be studied to confirm these two hypotheses.

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East Lake, located at Cape Bounty (Melville Island, Canadian High Arctic), was mapped using a high-resolution swath bathymetric sonar and a 12 kHz sub-bottom profiler, allowing for the first time the imaging of widespread occurrence of mass movement deposits (MMDs) in a Canadian High Arctic Lake. Mass movements occurred mostly on steep slopes located away from deltaic sedimentation. The marine to lacustrine transition in the sediment favours the generation of mass movements where the underlying massive mud appears to act as a gliding surface for the overlying varved deposits. Based on acoustic stratigraphy, we have identified at least two distinct events that triggered failures in the lake during the last 2000 years. The synchronicity of multiple failures and their widespread distribution suggest a seismic origin that could be related to the nearby Gustaf-Lougheed Arch seismic zone. Further sedimentological investigations on the MMDs are however required to confirm their age and origin.

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The transition of epithelial-like tumour cells to those exhibiting mesenchymal characteristics (Epithelial-to-mesenchymal Transition; EMT) is an integral process in breast cancer metastasis. EMT can be promoted by Transforming growth factor-beta (TGF-β) which can be found at high levels in the tumour stroma. Tumour-associated macrophages (TAMs) can also induce EMT in breast cancer cells, which is one way that they promote breast cancer metastasis. Vitamin D signalling has been implicated in EMT suppression and plays a role in modulating macrophage differentiation and stimulating their anti-inflammatory functions. This project had two major aims. First, we aimed to create and verify a unique fluorescent reporter gene construct designed to evaluate the dynamics of EMT in real-time and at the single-cell level. While some components of this reporter system were successfully validated, work to complete the final reporter construct is ongoing. The second and main aspect of this project focused on exploring the ability of 1,25-dihydroxyvitamin D3 (1,25D3) to modulate the interaction between mesenchymal mammary tumour cells and TAMs. Unexpectedly, in short-term treatment (48 hours) studies of 4T1 murine mammary tumour cells, we observed that 1,25D3 and TGF-β signalling work together to increase expression of the mesenchymal markers, Snai1, Fn1, and Col1a1. 1,25D3 and TGF-β also synergistically activate transcription of the gene encoding the 1,25D3-catabolizing enzyme, Cyp24a1. The ability of 1,25D3 and TGF-β to enhance expression of these genes was diminished in a long-term treatment (14 days) of 4T1 cells, and this effect was accompanied by a decrease in cell proliferation. 1,25D3 may also cooperate with cytokines produced by normal macrophages and macrophages considered to be TAM-like. Conditioned media experiments revealed that in the presence of factors from normal macrophages, 1,25D3 enhanced expression of Fn1, and in the presence of factors from TAM-like macrophages, 1,25D3 enhanced expression of Fn1 and Cyp24a1. Rather than mitigating the interaction as hypothesized, 1,25D3 may exacerbate the tumour-promoting effects of the EMT-TAM relationship. Also, signalling pathways involved in the EMT-TAM relationship may synergize with 1,25D3 to upregulate Cyp24a1 expression. These findings are important for understanding the potential of vitamin D compounds to be used in the treatment of breast cancer.

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A large eddy simulation is performed to study the deflagration to detonation transition phenomenon in an obstructed channel containing premixed stoichiometric hydrogen–air mixture. Two-dimensional filtered reactive Navier–Stokes equations are solved utilizing the artificially thickened flame approach (ATF) for modeling sub-grid scale combustion. To include the effect of induction time, a 27-step detailed mechanism is utilized along with an in situ adaptive tabulation (ISAT) method to reduce the computational cost due to the detailed chemistry. The results show that in the slow flame propagation regime, the flame–vortex interaction and the resulting flame folding and wrinkling are the main mechanisms for the increase of the flame surface and consequently acceleration of the flame. Furthermore, at high speed, the major mechanisms responsible for flame propagation are repeated reflected shock–flame interactions and the resulting baroclinic vorticity. These interactions intensify the rate of heat release and maintain the turbulence and flame speed at high level. During the flame acceleration, it is seen that the turbulent flame enters the ‘thickened reaction zones’ regime. Therefore, it is necessary to utilize the chemistry based combustion model with detailed chemical kinetics to properly capture the salient features of the fast deflagration propagation.