207 resultados para II inhibitor
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In this paper, a space fractional di®usion equation (SFDE) with non- homogeneous boundary conditions on a bounded domain is considered. A new matrix transfer technique (MTT) for solving the SFDE is proposed. The method is based on a matrix representation of the fractional-in-space operator and the novelty of this approach is that a standard discretisation of the operator leads to a system of linear ODEs with the matrix raised to the same fractional power. Analytic solutions of the SFDE are derived. Finally, some numerical results are given to demonstrate that the MTT is a computationally e±cient and accurate method for solving SFDE.
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An installation of sculptural objects that combine references to the portrait bust, drapery and socle with quotidian and incidental objects from the artist's studio. The work form part of the artist's ongoing self-portrait project in which he enacts formal strategies for tempering the authority conveyed by the self-portrait as an artistic genre.
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Two current longitudinal studies in advanced countries, PSED II in the US and CAUSEE in Australia, have attempted to harmonize the major features of the research design. A comparison of the initial screening and first detailed interviews indicates a higher participation in new firm creation in the U.S. Similar types of persons are involved in both countries, albeit more immigrants, older individuals with more work experience and more established individuals in Australia. The nascent enterprises in the two countries are similar on many characteristics, although those in Australia report greater emphasis on new technology and international customers. Assessment of the prevalence of nascent enterprises and new firms from the Global Entrepreneurship Monitor surveys indicates a higher prevalence of new firms in Australia. These two longitudinal projects may help determine if this reflects a high proportion of new firm births or greater survival in the early years among Australian new firms.
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This paper is a continuation of the paper titled “Concurrent multi-scale modeling of civil infrastructure for analyses on structural deteriorating—Part I: Modeling methodology and strategy” with the emphasis on model updating and verification for the developed concurrent multi-scale model. The sensitivity-based parameter updating method was applied and some important issues such as selection of reference data and model parameters, and model updating procedures on the multi-scale model were investigated based on the sensitivity analysis of the selected model parameters. The experimental modal data as well as static response in terms of component nominal stresses and hot-spot stresses at the concerned locations were used for dynamic response- and static response-oriented model updating, respectively. The updated multi-scale model was further verified to act as the baseline model which is assumed to be finite-element model closest to the real situation of the structure available for the subsequent arbitrary numerical simulation. The comparison of dynamic and static responses between the calculated results by the final model and measured data indicated the updating and verification methods applied in this paper are reliable and accurate for the multi-scale model of frame-like structure. The general procedures of multi-scale model updating and verification were finally proposed for nonlinear physical-based modeling of large civil infrastructure, and it was applied to the model verification of a long-span bridge as an actual engineering practice of the proposed procedures.
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The role that heparanase plays during metastasis and angiogenesis in tumors makes it an attractive target for cancer therapeutics. Despite this enzyme’s significance, most of the assays developed to measure its activity are complex. Moreover, they usually rely on labeling variable preparations of the natural substrate heparan sulfate, making comparisons across studies precarious. To overcome these problems, we have developed a convenient assay based on the cleavage of the synthetic heparin oligosaccharide fondaparinux. The assay measures the appearance of the disaccharide product of heparanase-catalyzed fondaparinux cleavage colorimetrically using the tetrazolium salt WST-1. Because this assay has a homogeneous substrate with a single point of cleavage, the kinetics of the enzyme can be reliably characterized, giving a Km of 46 μM and a kcat of 3.5 s−1 with fondaparinux as substrate. The inhibition of heparanase by the published inhibitor, PI-88, was also studied, and a Ki of 7.9 nM was determined. The simplicity and robustness of this method, should, not only greatly assist routine assay of heparanase activity but also could be adapted for high-throughput screening of compound libraries, with the data generated being directly comparable across studies.
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An improved synthetic route to α(1→3)/α(1→2)-linked mannooligosaccharides has been developed and applied to a more efficient preparation of the potent anti-angiogenic sulfated pentasaccharide, benzyl Manα(1→3)-Manα(1→3)-Manα(1→3)-Manα(1→2)-Man hexadecasulfate, using only two monosaccharide building blocks. Of particular note are improvements in the preparation of both building blocks and a simpler, final deprotection strategy. The route also provides common intermediates for the introduction of aglycones other than benzyl, either at the building block stage or after oligosaccharide assembly. The anti-angiogenic activity of the synthesized target compound was confirmed via the rat aortic assay.
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Height is a complex physical trait that displays strong heritability. Adult height is related to length of the long bones, which is determined by growth at the epiphyseal growth plate. Longitudinal bone growth occurs via the process of endochondral ossification, where bone forms over the differentiating cartilage template at the growth plate. Estrogen plays a major role in regulating longitudinal bone growth and is responsible for inducing the pubertal growth spurt and fusion of the epiphyseal growth plate. However, the mechanism by which estrogen promotes epiphyseal fusion is poorly understood. It has been hypothesised that estrogen functions to regulate growth plate fusion by stimulating chondrocyte apoptosis, angiogenesis and bone cell invasion in the growth plate. Another theory has suggested that estrogen exposure exhausts the proliferative capacity of growth plate chondrocytes, which accelerates the process of chondrocyte senescence, leading to growth plate fusion. The overall objective of this study was to gain a greater understanding of the molecular mechanisms behind estrogen-mediated growth and height attainment by examining gene regulation in chondrocytes and the role of some of these genes in normal height inheritance. With the heritability of height so well established, the initial hypothesis was that genetic variation in candidate genes associated with longitudinal bone growth would be involved in normal adult height variation. The height-related genes FGFR3, CBFA1, ER and CBFA1 were screened for novel polymorphisms using denaturing HPLC and RFLP analysis. In total, 24 polymorphisms were identified. Two SNPs in ER (rs3757323 C>T and rs1801132 G>C) were strongly associated with adult male height and displayed an 8 cm and 9 cm height difference between homozygous genotypes, respectively. The TC haplotype of these SNPs was associated with a 6 cm decrease in height and remarkably, no homozygous carriers of the TC haplotype were identified in tall subjects. No significant associations with height were found for polymorphisms in the FGFR3, CBFA1 or VDR genes. In the epiphyseal growth plate, chondrocyte proliferation, matrix synthesis and chondrocyte hypertrophy are all major contributors to long bone growth. As estrogen plays such a significant role in both growth and final height attainment, another hypothesis of this study was that estrogen exerted its effects in the growth plate by influencing chondrocyte proliferation and mediating the expression of chondrocyte marker genes. The examination of genes regulated by estrogen in chondrocyte-like cells aimed to identify potential regulators of growth plate fusion, which may further elucidate mechanisms involved in the cessation of linear growth. While estrogen did not dramatically alter the proliferation of the SW1353 cell line, gene expression experiments identified several estrogen regulated genes. Sixteen chondrocyte marker genes were examined in response to estrogen concentrations ranging from 10-12 M to 10-8 M over varying time points. Of the genes analysed, IHH, FGFR3, collagen II and collagen X were not readily detectable and PTHrP, GHR, ER, BMP6, SOX9 and TGF1 mRNAs showed no significant response to estrogen treatments. However, the expression of MMP13, CBFA1, BCL-2 and BAX genes were significantly decreased. Interestingly, the majority of estrogen regulated genes in SW1353 cells are expressed in the hypertrophic zone of the growth plate. Estrogen is also known to regulate systemic GH secretion and local GH action. At the molecular level, estrogen functions to inhibit GH action by negatively regulating GH signalling. GH treated SW1353 cells displayed increases in MMP9 mRNA expression (4.4-fold) and MMP13 mRNA expression (64-fold) in SW1353 cells. Increases were also detected in their respective proteins. Treatment with AG490, an established JAK2 inhibitor, blocked the GH mediated stimulation of both MMP9 and MMP13 mRNA expression. The application of estrogen and GH to SW1353 cells attenuated GH-stimulated MMP13 levels, but did not affect MMP9 levels. Investigation of GH signalling revealed that SW1353 cells have high levels of activated JAK2 and exposure to GH, estrogen, AG490 and other signalling inhibitors did not affect JAK2 phosphorylation. Interestingly, AG490 treatment dramatically decreased ERK2 signalling, although GH did stimulate ERK2 phosphorylation above control levels. AG490 also decreased CBFA1 expression, a transcription factor known to activate MMP9 and MMP13. Finally, GH and estrogen treatment increased expression of SOCS3 mRNA, suggesting that SOCS3 may regulate JAK/STAT signalling in SW1353 cells. The modulation of GH-mediated MMP expression by estrogen in SW1353 cells represents a potentially novel mechanism by which estrogen may regulate longitudinal bone growth. However, further investigation is required in order to elucidate the precise mechanisms behind estrogen and GH regulation of MMP13 expression in SW1353 cells. This study has provided additional evidence that estrogen and the ER gene are major factors in the regulation of growth and the determination of adult height. Newly identified polymorphisms in the ER gene not only contribute to our understanding of the genetic basis of human height, but may also be useful in association studies examining other complex traits. This study also identified several estrogen regulated genes and indicated that estrogen modifies the expression of genes which are primarily expressed in the hypertrophic region of the epiphyseal growth plate. Furthermore, synergistic studies incorporating GH and estrogen have revealed the ability of estrogen to attenuate the effects of GH on MMP13 expression, revealing potential pathways by which estrogen may modulate growth plate fusion, longitudinal bone growth and even arthritis.
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Teaching to an international audience online can be significantly different as compared to a traditional classroom setting. In a traditional classroom setting, the students are usually removed from their own cultural context and required to operate in the lecturer’s context. International students coming to Malaysia to study are implicitly expected to, and often do, become familiar with the Malaysian culture and style of education. The use of educational technologies as a blended strategy in higher education programs offers challenges and opportunities for all students but this may be different for international students who come from varied backgrounds. With an increasingly competitive global demand for higher education, Malaysian institutions strive to be the hub of educational excellence and a preferred option for international students in coping with the challenges of studying abroad in a different culture. This research will evaluate how undergraduate students perceive their online learning experiences in a Malaysian institute. The OLES (Online Learning Environment Survey) will be used to explore the international and domestic students’ perception on e-learning and the findings of the last six OLES scales varying from (Equity, Enjoyment, Asychronocity, Evaluation & Assessments, Online Learning Tools, and Interface Design) will be reported in this research. An in-depth study will be conducted to compare and contrast the challenges of international students with domestic students. Major difficulties encountered and how these students actually cope with e-learning, as well as the strategies and tools used to overcome the challenges will be investigated.
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The two outcome indices described in a companion paper (Sanson et al., Child Indicators Research, 2009) were developed using data from the Longitudinal Study of Australian Children (LSAC). These indices, one for infants and the other for 4 year to 5 year old children, were designed to fill the need for parsimonious measures of children’s developmental status to be used in analyses by a broad range of data users and to guide government policy and interventions to support young children’s optimal development. This paper presents evidence from Wave 1data from LSAC to support the validity of these indices and their three domain scores of Physical, Social/Emotional, and Learning. Relationships between the indices and child, maternal, family, and neighborhood factors which are known to relate concurrently to child outcomes were examined. Meaningful associations were found with the selected variables, thereby demonstrating the usefulness of the outcome indices as tools for understanding children’s development in their family and socio-cultural contexts. It is concluded that the outcome indices are valuable tools for increasing understanding of influences on children’s development, and for guiding policy and practice to optimize children’s life chances.
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The unusual (1:1) complex ‘adduct’ salt of copper(II) with 4,5-dichlorophthalic acid (H2DCPA), having formula [Cu(H2O)4(C8H3Cl2O4) (C8H4Cl2O4)] . (C8H3Cl2O4) has been synthesized and characterized using single-crystal X-ray diffraction. Crystals are monoclinic, space group P21/c, with Z = 4 in a cell with dimensions a = 20.1376(7), b =12.8408(4) c = 12.1910(4) Å, β = 105.509(4)o. The complex is based on discrete tetragonally distorted octahedral [CuO6] coordination centres with the four water ligands occupying the square planar sites [Cu-O, 1.962(4)-1.987(4) Å] and the monodentate carboxyl-O donors of two DCPA ligand species in the axial sites. The first of these bonds [Cu-O, 2.341(4) Å] is with an oxygen of a HDCPA monoanion, the second with an oxygen of a H2DCPA acid species [Cu-O, 2.418(4) Å]. The un-coordinated ‘adduct’ molecule is a HDCPA counter anion which is strongly hydrogen-bonded to the coordinated H2DCPA ligand [O… O, 2.503(6) Å] while a number of peripheral intra- and intermolecular hydrogen-bonding interactions give a two-dimensional network structure.
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Adiabatic compression testing of components in gaseous oxygen is a test method that is utilized worldwide and is commonly required to qualify a component for ignition tolerance under its intended service. This testing is required by many industry standards organizations and government agencies; however, a thorough evaluation of the test parameters and test system influences on the thermal energy produced during the test has not yet been performed. This paper presents a background for adiabatic compression testing and discusses an approach to estimating potential differences in the thermal profiles produced by different test laboratories. A “Thermal Profile Test Fixture” (TPTF) is described that is capable of measuring and characterizing the thermal energy for a typical pressure shock by any test system. The test systems at Wendell Hull & Associates, Inc. (WHA) in the USA and at the BAM Federal Institute for Materials Research and Testing in Germany are compared in this manner and some of the data obtained is presented. The paper also introduces a new way of comparing the test method to idealized processes to perform system-by-system comparisons. Thus, the paper introduces an “Idealized Severity Index” (ISI) of the thermal energy to characterize a rapid pressure surge. From the TPTF data a “Test Severity Index” (TSI) can also be calculated so that the thermal energies developed by different test systems can be compared to each other and to the ISI for the equivalent isentropic process. Finally, a “Service Severity Index” (SSI) is introduced to characterizing the thermal energy of actual service conditions. This paper is the second in a series of publications planned on the subject of adiabatic compression testing.
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The application of near-infrared and infrared spectroscopy has been used for identification and distinction of basic Cu-sulphates that include devilline, chalcoalumite and caledonite. Near-infrared spectra of copper sulphate minerals confirm copper in divalent state. Jahn-Teller effect is more significant in chalcoalumite where 2B1g ® 2B2g transition band shows a larger splitting (490 cm-1) confirming more distorted octahedral coordination of Cu2+ ion. One symmetrical band at 5145 cm-1 with shoulder band 5715 cm-1 result from the absorbed molecular water in the copper complexes are the combinations of OH vibrations of H2O. One sharp band at around 3400 cm-1 in IR common to the three complexes is evidenced by Cu-OH vibrations. The strong absorptions observed at 1685 and 1620 cm-1 for water bending modes in two species confirm strong hydrogen bonding in devilline and chalcoalumite. The multiple bands in v3 and v4(SO4)2- stretching regions are attributed to the reduction of symmetry to the sulphate ion from Td to C2V. Chalcoalumite, the excellent IR absorber over the range 3800-500 cm-1 is treated as most efficient heat insulator among the Cu-sulphate complexes.