433 research outputs found

    Resonances and Surface Waves in Elastic Wave Scattering from Cavities and Inclusions

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    Elastic-wave scattering from various types of cavities and inclusions has been studied theoretically with special emphasis on surface wave effects that appear during the scattering process. Resonances in the scattering amplitudes are caused by the phase matching of circumnavigating surface waves, and manifest themselves as poles in the complex frequency plane that correspond to the (complex) eigenfrequencies of the cavity of inclusion. These results are most easily obtained for scatterers of separable geometry, such as spheres, where theoretical amplitudes are well-known. Here, the formalism for a complete treatment of elastic-wave scattering from infinite cylindrical cavities and solid inclusions has been worked out for general oblique incidence. Poles of scattering amplitudes have been found for evacuated and for fluid-filled cylinders, and have been physically interpreted in terms of helical surface waves propagating both interior and exterior to the cylinder. Dispersion, attenuation, and refraction of these surface waves have been obtained. Progressing to more generally-shaped obstacles, we have studied surface waves and complex-frequency poles for finite- length cylindrical cavities with flat ends. In this fashion, the resonance features(particularly the cavity eigenfrequencies) that appear prominently in the scattering amplitude can be understood as to their physical origin and their dependence on the type of cavity, and may be exploited for purposes of classification and identification of flaws by their ultrasonic resonances (ultrasonic “resonance spectroscopy”)

    A Heart-Hand Syndrome Gene: Tfap2b Plays a Critical Role in the Development and Remodeling of Mouse Ductus Arteriosus and Limb Patterning

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    BACKGROUND: Patent ductus arteriosus (PDA) is one of the most common forms of congenital heart disease. Mutations in transcription factor TFAP2B cause Char syndrome, a human disorder characterized by PDA, facial dysmorphysm and hand anomalies. Animal research data are needed to understand the mechanisms. The aim of our study was to elucidate the pathogenesis of Char syndrome at the molecular level. METHODOLOGY/PRINCIPAL FINDINGS: Gene expression of Tfap2b during mouse development was studied, and newborns of Tfap2b-deficient mice were examined to identify phenotypes. Gel shift assays had been carried out to search for Tfap2 downstream genes. Promoters of candidate genes were cloned into a reporter construct and used to demonstrate their regulation by Tfap2b in cell transfection. In situ hybridizations showed that the murine transcription factor Tfap2b was expressed during the entire development of mouse ductus arteriosus. Histological examination of ductus arteriosus from Tfap2b knockout mice 6 hours after birth revealed that they were not closed. Consequently, the lungs of Tfap2b(-/-) mice demonstrated progressive congestion of the pulmonary capillaries, which was postulated to result secondarily from PDA. In addition, Tfap2b was expressed in the limb buds, particularly in the posterior limb field during development. Lack of Tfap2b resulted in bilateral postaxial accessory digits. Further study indicated that expressions of bone morphogenetic protein (Bmp) genes, which are reported to be involved in the limb patterning and ductal development, were altered in limb buds of Tfap2b-deficient embryos, due to direct control of Bmp2 and Bmp4 promoter activity by Tfap2b. CONCLUSIONS/SIGNIFICANCE: Tfap2b plays important roles in the development of mouse ductus arteriosus and limb patterning. Loss of Tfap2b results in altered Bmp expression that may cause the heart-limb defects observed in Tfap2b mouse mutants and Char syndrome patients. The Tfap2b knockout mouse may add to the very limited available animal models of PDA

    Improving response rates using a monetary incentive for patient completion of questionnaires: an observational study

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    Background: Poor response rates to postal questionnaires can introduce bias and reduce the statistical power of a study. To improve response rates in our trial in primary care we tested the effect of introducing an unconditional direct payment of 5 pound for the completion of postal questionnaires. Methods: We recruited patients in general practice with knee problems from sites across the United Kingdom. An evidence-based strategy was used to follow-up patients at twelve months with postal questionnaires. This included an unconditional direct payment of 5 pound to patients for the completion and return of questionnaires. The first 105 patients did not receive the 5 pound incentive, but the subsequent 442 patients did. We used logistic regression to analyse the effect of introducing a monetary incentive to increase the response to postal questionnaires. Results: The response rate following reminders for the historical controls was 78.1% ( 82 of 105) compared with 88.0% ( 389 of 442) for those patients who received the 5 pound payment (diff = 9.9%, 95% CI 2.3% to 19.1%). Direct payments significantly increased the odds of response ( adjusted odds ratio = 2.2, 95% CI 1.2 to 4.0, P = 0.009) with only 12 of 442 patients declining the payment. The incentive did not save costs to the trial - the extra cost per additional respondent was almost 50 pound. Conclusion: The direct payment of 5 pound significantly increased the completion of postal questionnaires at negligible increase in cost for an adequately powered study

    The mixed problem for the Laplacian in Lipschitz domains

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    We consider the mixed boundary value problem or Zaremba's problem for the Laplacian in a bounded Lipschitz domain in R^n. We specify Dirichlet data on part of the boundary and Neumann data on the remainder of the boundary. We assume that the boundary between the sets where we specify Dirichlet and Neumann data is a Lipschitz surface. We require that the Neumann data is in L^p and the Dirichlet data is in the Sobolev space of functions having one derivative in L^p for some p near 1. Under these conditions, there is a unique solution to the mixed problem with the non-tangential maximal function of the gradient of the solution in L^p of the boundary. We also obtain results with data from Hardy spaces when p=1.Comment: Version 5 includes a correction to one step of the main proof. Since the paper appeared long ago, this submission includes the complete paper, followed by a short section that gives the correction to one step in the proo

    Investigation of low 5-year relative survival for breast cancer in a London cancer network

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    BACKGROUND: Breast cancer 5-year relative survival is low in the North East London Cancer Network (NELCN). METHODS: We compared breast cancer that was diagnosed during 2001-2005 with that in the rest of London. RESULTS: North East London Cancer Network women more often lived in socioeconomic quintile 5 (42 vs 21%) and presented with advanced disease (11 vs 7%). Cox regression analysis showed the survival difference (hazard ratio: 1.27, 95% confidence interval (CI): 1.15-1.41) reduced to 1.00 (95% CI: 0.89-1.11) after adjustment for age, stage, socioeconomic deprivation, ethnicity and treatment. Major drivers were stage and deprivation. Excess mortality was in the first year. CONCLUSION: Late diagnosis occurs in NELCN

    Kindlins, Integrin Activation and the Regulation of Talin Recruitment to αIIbβ3

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    Talins and kindlins bind to the integrin β3 cytoplasmic tail and both are required for effective activation of integrin αIIbβ3 and resulting high-affinity ligand binding in platelets. However, binding of the talin head domain alone to β3 is sufficient to activate purified integrin αIIbβ3 in vitro. Since talin is localized to the cytoplasm of unstimulated platelets, its re-localization to the plasma membrane and to the integrin is required for activation. Here we explored the mechanism whereby kindlins function as integrin co-activators. To test whether kindlins regulate talin recruitment to plasma membranes and to αIIbβ3, full-length talin and kindlin recruitment to β3 was studied using a reconstructed CHO cell model system that recapitulates agonist-induced αIIbβ3 activation. Over-expression of kindlin-2, the endogenous kindlin isoform in CHO cells, promoted PAR1-mediated and talin-dependent ligand binding. In contrast, shRNA knockdown of kindlin-2 inhibited ligand binding. However, depletion of kindlin-2 by shRNA did not affect talin recruitment to the plasma membrane, as assessed by sub-cellular fractionation, and neither over-expression of kindlins nor depletion of kindlin-2 affected talin interaction with αIIbβ3 in living cells, as monitored by bimolecular fluorescence complementation. Furthermore, talin failed to promote kindlin-2 association with αIIbβ3 in CHO cells. In addition, purified talin and kindlin-3, the kindlin isoform expressed in platelets, failed to promote each other's binding to the β3 cytoplasmic tail in vitro. Thus, kindlins do not promote initial talin recruitment to αIIbβ3, suggesting that they co-activate integrin through a mechanism independent of recruitment

    Drosophila S2 Cells Are Non-Permissive for Vaccinia Virus DNA Replication Following Entry via Low pH-Dependent Endocytosis and Early Transcription

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    Vaccinia virus (VACV), a member of the chordopox subfamily of the Poxviridae, abortively infects insect cells. We have investigated VACV infection of Drosophila S2 cells, which are useful for protein expression and genome-wide RNAi screening. Biochemical and electron microscopic analyses indicated that VACV entry into Drosophila S2 cells depended on the VACV multiprotein entry-fusion complex but appeared to occur exclusively by a low pH-dependent endocytic mechanism, in contrast to both neutral and low pH entry pathways used in mammalian cells. Deep RNA sequencing revealed that the entire VACV early transcriptome, comprising 118 open reading frames, was robustly expressed but neither intermediate nor late mRNAs were made. Nor was viral late protein synthesis or inhibition of host protein synthesis detected by pulse-labeling with radioactive amino acids. Some reduction in viral early proteins was noted by Western blotting. Nevertheless, synthesis of the multitude of early proteins needed for intermediate gene expression was demonstrated by transfection of a plasmid containing a reporter gene regulated by an intermediate promoter. In addition, expression of a reporter gene with a late promoter was achieved by cotransfection of intermediate genes encoding the late transcription factors. The requirement for transfection of DNA templates for intermediate and late gene expression indicated a defect in viral genome replication in VACV-infected S2 cells, which was confirmed by direct analysis. Furthermore, VACV-infected S2 cells did not support the replication of a transfected plasmid, which occurs in mammalian cells and is dependent on all known viral replication proteins, indicating a primary restriction of DNA synthesis

    Estimating attendance for breast cancer screening in ethnic groups in London

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    BACKGROUND: Breast screening uptake in London is below the Government's target of 70% and we investigate whether ethnicity affects this. Information on the ethnicity for the individual women invited is unavailable, so we use an area-based method similar to that routinely used to derive a geographical measure for socioeconomic deprivation. METHODS: We extracted 742,786 observations on attendance for routine appointments between 2004 and 2007 collected by the London Quality Assurance Reference Centre. Each woman was assigned to a lower super output (LSOA) based on her postcode of residence. The proportions of the ethnic groups within each LSOA are known, so that the likelihood of a woman belonging to White, Black and Asian groups can be assigned. We investigated screening attendance by age group, socioeconomic deprivation using the Index of Deprivation 2004 income quintile, invitation type and breast screening service. Using logistic regression analysis we calculated odds ratios for attendance based on ethnic composition of the population, adjusting for age, socioeconomic status, the invitation type and screening service. RESULTS: The unadjusted attendance odds ratios were high for the White population (OR: 3.34 95% CI [3.26-3.42]) and low for the Black population (0.13 [0.12-0.13]) and the Asian population (0.55 [0.53-0.56]). Multivariate adjustment reduced the differences, but the Black population remained below unity (0.47 [0.44-0.50]); while the White (1.30 [1.26-1.35]) and Asian populations (1.10 [1.05-1.15]) were higher. There was little difference in the attendance between age groups. Attendance was highest for the most affluent group and fell sharply with increasing deprivation. For invitation type, the routine recall was higher than the first call. There were wide variations in the attendance for different ethnic groups between the individual screening services. CONCLUSIONS: Overall breast screening attendance is low in communities with large Black populations, suggesting the need to improve participation of Black women. Variations in attendance for the Asian population require further investigation at an individual screening service level

    Woodland Recovery after Suppression of Deer: Cascade effects for Small Mammals, Wood Mice (Apodemus sylvaticus) and Bank Voles (Myodes glareolus)

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    Over the past century, increases in both density and distribution of deer species in the Northern Hemisphere have resulted in major changes in ground flora and undergrowth vegetation of woodland habitats, and consequentially the animal communities that inhabit them. In this study, we tested whether recovery in the vegetative habitat of a woodland due to effective deer management (from a peak of 0.4–1.5 to <0.17 deer per ha) had translated to the small mammal community as an example of a higher order cascade effect. We compared deer-free exclosures with neighboring open woodland using capture-mark-recapture (CMR) methods to see if the significant difference in bank vole (Myodes glareolus) and wood mouse (Apodemus sylvaticus) numbers between these environments from 2001–2003 persisted in 2010. Using the multi-state Robust Design method in program MARK we found survival and abundance of both voles and mice to be equivalent between the open woodland and the experimental exclosures with no differences in various metrics of population structure (age structure, sex composition, reproductive activity) and individual fitness (weight), although the vole population showed variation both locally and temporally. This suggests that the vegetative habitat - having passed some threshold of complexity due to lowered deer density - has allowed recovery of the small mammal community, although patch dynamics associated with vegetation complexity still remain. We conclude that the response of small mammal communities to environmental disturbance such as intense browsing pressure can be rapidly reversed once the disturbing agent has been removed and the vegetative habitat is allowed to increase in density and complexity, although we encourage caution, as a source/sink dynamic may emerge between old growth patches and the recently disturbed habitat under harsh conditions
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