412 research outputs found

    On the microlocal properties of the range of systems of principal type

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    The purpose of this paper is to study microlocal conditions for inclusion relations between the ranges of square systems of pseudodifferential operators which fail to be locally solvable. The work is an extension of earlier results for the scalar case in this direction, where analogues of results by L. H\"ormander about inclusion relations between the ranges of first order differential operators with coefficients in C∞C^\infty which fail to be locally solvable were obtained. We shall study the properties of the range of systems of principal type with constant characteristics for which condition (\Psi) is known to be equivalent to microlocal solvability.Comment: Added Theorem 4.7, Corollary 4.8 and Lemma A.4, corrected misprints. The paper has 40 page

    Solvability of subprincipal type operators

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    In this paper we consider the solvability of pseudodifferential operators in the case when the principal symbol vanishes of order k≥2k \ge 2 at a nonradial involutive manifold Σ2\Sigma_2. We shall assume that the operator is of subprincipal type, which means that the k k:th inhomogeneous blowup at Σ2\Sigma_2 of the refined principal symbol is of principal type with Hamilton vector field parallel to the base Σ2\Sigma_2, but transversal to the symplectic leaves of Σ2\Sigma_2 at the characteristics. When k=∞k = \infty this blowup reduces to the subprincipal symbol. We also assume that the blowup is essentially constant on the leaves of Σ2\Sigma_2, and does not satisfying the Nirenberg-Treves condition (Ψ{\Psi}). We also have conditions on the vanishing of the normal gradient and the Hessian of the blowup at the characteristics. Under these conditions, we show that PP is not solvable.Comment: Changed the formulation of Theorem 2.15, added an assuption. Corrected errors and clarified the arguments. Added reference

    Accumulation of 125I-labelled thiouracil and propylthiouracil in murine melanotic melanomas.

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    We have shown that thioamides are incorporated as false precursors into melanin during its synthesis. To be clinically useful in the diagnosis or therapy of melanotic melanomas, they would have to be tagged with an appropriate isotope or possibly a cytotoxic moiety. 125I-Thiouracil (125I-TU) is here shown to be accumulated in the melanin of melanotic melanomas transplanted into mice in a similar way as is 14C-thiouracil (14C-TU). 125I-TU gives tumour/liver and tumour/muscle ratios up to 22 and 778 respectively, at 4 days after administration. 125I-TU is accumulated by melanoma cells in vitro more effectively than 14C-TU (125I-TU/14C-TU, 2.7), while the in vivo accumulation into melanomas is slightly lower for 125I-TU as compared to 14C-TU (125I-TU/14C-TU, 0.35). This appears to be due to a partial deiodination (less than 14% of the dose within 4 days) and probably a more rapid excretion of 125I-TU or its metabolite(s). The accumulation of radioactivity in the thyroid can essentially be eliminated by pretreatment with potassium iodide and/or thyroxine. 125I-Propylthiouracil is also accumulated in melanotic melanoma cells in vivo and in vitro, but at a lower level than in 125I-TU and 14C-TU

    Cardiorespiratory fitness is associated with hard and light intensity physical activity but not time spent sedentary in 10–14 year old schoolchildren: the HAPPY study

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    Sedentary behaviour is a major risk factor for developing chronic diseases and is associated with low cardiorespiratory fitness in adults. It remains unclear how sedentary behaviour and different physical activity subcomponents are related to cardiorespiratory fitness in children. The purpose of this study was to assess how sedentary behaviour and different physical activity subcomponents are associated with 10–14 year-old schoolchildren's cardiorespiratory fitness

    Associations of sedentary behaviour, physical activity, blood pressure and anthropometric measures with cardiorespiratory fitness in children with cerebral palsy

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    Background - Children with cerebral palsy (CP) have poor cardiorespiratory fitness in comparison to their peers with typical development, which may be due to low levels of physical activity. Poor cardiorespiratory fitness may contribute to increased cardiometabolic risk. Purpose - The aim of this study was to determine the association between sedentary behaviour, physical activity and cardiorespiratory fitness in children with CP. An objective was to determine the association between cardiorespiratory fitness, anthropometric measures and blood pressure in children with CP. Methods- This study included 55 ambulatory children with CP [mean (SD) age 11.3 (0.2) yr, range 6-17 yr; Gross Motor Function Classification System (GMFCS) levels I and II]. Anthropometric measures (BMI, waist circumference and waist-height ratio) and blood pressure were taken. Cardiorespiratory fitness was measured using a 10 m shuttle run test. Children were classified as low, middle and high fitness according to level achieved on the test using reference curves. Physical activity was measured by accelerometry over 7 days. In addition to total activity, time in sedentary behaviour and light, moderate, vigorous, and sustained moderate-to-vigorous activity (≥10 min bouts) were calculated. Results - Multiple regression analyses revealed that vigorous activity (β = 0.339, p<0.01), sustained moderate-to-vigorous activity (β = 0.250, p<0.05) and total activity (β = 0.238, p<0.05) were associated with level achieved on the shuttle run test after adjustment for age, sex and GMFCS level. Children with high fitness spent more time in vigorous activity than children with middle fitness (p<0.05). Shuttle run test level was negatively associated with BMI (r2 = -0.451, p<0.01), waist circumference (r2 = -0.560, p<0.001), waist-height ratio (r2 = -0.560, p<0.001) and systolic blood pressure (r2 = -0.306, p<0.05) after adjustment for age, sex and GMFCS level. Conclusions - Participation in physical activity, particularly at a vigorous intensity, is associated with high cardiorespiratory fitness in children with CP. Low cardiorespiratory fitness is associated with increased cardiometabolic risk

    Upregulation of CRABP1 in human neuroblastoma cells overproducing the Alzheimer-typical Aβ42 reduces their differentiation potential

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    <p>Abstract</p> <p>Background</p> <p>Alzheimer's disease (AD) is characterized by neurodegeneration and changes in cellular processes, including neurogenesis. Proteolytic processing of the amyloid precursor protein (APP) plays a central role in AD. Owing to varying APP processing, several β-amyloid peptides (Aβ) are generated. In contrast to the form with 40 amino acids (Aβ<sub>40</sub>), the variant with 42 amino acids (Aβ<sub>42</sub>) is thought to be the pathogenic form triggering the pathological cascade in AD. While total-Aβ effects have been studied extensively, little is known about specific genome-wide effects triggered by Aβ<sub>42 </sub>or Aβ<sub>40 </sub>derived from their direct precursor C99.</p> <p>Methods</p> <p>A combined transcriptomics/proteomics analysis was performed to measure the effects of intracellularly generated Aβ peptides in human neuroblastoma cells. Data was validated by real-time polymerase chain reaction (real-time PCR) and a functional validation was carried out using RNA interference.</p> <p>Results</p> <p>Here we studied the transcriptomic and proteomic responses to increased or decreased Aβ<sub>42 </sub>and Aβ<sub>40 </sub>levels generated in human neuroblastoma cells. Genome-wide expression profiles (Affymetrix) and proteomic approaches were combined to analyze the cellular response to the changed Aβ<sub>42</sub>- and Aβ<sub>40</sub>-levels. The cells responded to this challenge with significant changes in their expression pattern. We identified several dysregulated genes and proteins, but only the cellular retinoic acid binding protein 1 (CRABP1) was up-regulated exclusively in cells expressing an increased Aβ<sub>42</sub>/Aβ<sub>40 </sub>ratio. This consequently reduced all-trans retinoic acid (RA)-induced differentiation, validated by CRABP1 knock down, which led to recovery of the cellular response to RA treatment and cellular sprouting under physiological RA concentrations. Importantly, this effect was specific to the AD typical increase in the Aβ<sub>42</sub>/Aβ<sub>40 </sub>ratio, whereas a decreased ratio did not result in up-regulation of CRABP1.</p> <p>Conclusion</p> <p>We conclude that increasing the Aβ<sub>42</sub>/Aβ<sub>40 </sub>ratio up-regulates CRABP1, which in turn reduces the differentiation potential of the human neuroblastoma cell line SH-SY5Y, but increases cell proliferation. This work might contribute to the better understanding of AD neurogenesis, currently a controversial topic.</p
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