646 research outputs found

    Palindromic Decompositions with Gaps and Errors

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    Identifying palindromes in sequences has been an interesting line of research in combinatorics on words and also in computational biology, after the discovery of the relation of palindromes in the DNA sequence with the HIV virus. Efficient algorithms for the factorization of sequences into palindromes and maximal palindromes have been devised in recent years. We extend these studies by allowing gaps in decompositions and errors in palindromes, and also imposing a lower bound to the length of acceptable palindromes. We first present an algorithm for obtaining a palindromic decomposition of a string of length n with the minimal total gap length in time O(n log n * g) and space O(n g), where g is the number of allowed gaps in the decomposition. We then consider a decomposition of the string in maximal \delta-palindromes (i.e. palindromes with \delta errors under the edit or Hamming distance) and g allowed gaps. We present an algorithm to obtain such a decomposition with the minimal total gap length in time O(n (g + \delta)) and space O(n g).Comment: accepted to CSR 201

    Efficacy and Safety Comparison of Liraglutide, Glimepiride, and Placebo, All in Combination With Metformin, in Type 2 Diabetes: The LEAD (Liraglutide Effect and Action in Diabetes)-2 study

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    OBJECTIVE—The efficacy and safety of adding liraglutide (a glucagon-like peptide-1 receptor agonist) to metformin were compared with addition of placebo or glimepiride to metformin in subjects previously treated with oral antidiabetes (OAD) therapy

    Endogenous laminin is required for human airway smooth muscle cell maturation

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    BACKGROUND: Airway smooth muscle (ASM) contraction underlies acute bronchospasm in asthma. ASM cells can switch between a synthetic-proliferative phenotype and a contractile phenotype. While the effects of extracellular matrix (ECM) components on modulation of ASM cells to a synthetic phenotype have been reported, the role of ECM components on maturation of ASM cells to a contractile phenotype in adult lung is unclear. As both changes in ECM components and accumulation of contractile ASM are features of airway wall remodelling in asthma, we examined the role of the ECM protein, laminin, in the maturation of contractile phenotype in human ASM cells. METHODS: Human ASM cells were made senescence-resistant by stable expression of human telomerase reverse transcriptase. Maturation to a contractile phenotype was induced by 7-day serum deprivation, as assessed by immunoblotting for desmin and calponin. The role of laminin on ASM maturation was investigated by comparing the effects of exogenous laminin coated on culture plates, and of soluble laminin peptide competitors. Endogenous expression of laminin chains during ASM maturation was also measured. RESULTS: Myocyte binding to endogenously expressed laminin was required for ASM phenotype maturation, as laminin competing peptides (YIGSR or GRGDSP) significantly reduced desmin and calponin protein accumulation that otherwise occurs with prolonged serum deprivation. Coating of plastic cell culture dishes with different purified laminin preparations was not sufficient to further promote accumulation of desmin or calponin during 7-day serum deprivation. Expression of α2, β1 and γ1 laminin chains by ASM cells was specifically up-regulated during myocyte maturation, suggesting a key role for laminin-2 in the development of the contractile phenotype. CONCLUSION: While earlier reports suggest exogenously applied laminin slows the spontaneous modulation of ASM to a synthetic phenotype, we show for the first time that endogenously expressed laminin is required for ASM maturation to the contractile phenotype. As endogenously expressed laminin chains α2, β1 and γ1 are uniquely increased during myocyte maturation, these laminin chains may be key in this process. Thus, human ASM maturation appears to involve regulated endogenous expression of a select set of laminin chains that are essential for accumulation of contractile phenotype myocytes

    Augmentation of Neovascularizaiton in Hindlimb Ischemia by Combined Transplantation of Human Embryonic Stem Cells-Derived Endothelial and Mural Cells

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    BACKGROUND: We demonstrated that mouse embryonic stem (ES) cells-derived vascular endothelial growth factor receptor-2 (VEGF-R2) positive cells could differentiate into both endothelial cells (EC) and mural cells (MC), and termed them as vascular progenitor cells (VPC). Recently, we have established a method to expand monkey and human ES cells-derived VPC with the proper differentiation stage in a large quantity. Here we investigated the therapeutic potential of human VPC-derived EC and MC for vascular regeneration. METHODS AND RESULTS: After the expansion of human VPC-derived vascular cells, we transplanted these cells to nude mice with hindlimb ischemia. The blood flow recovery and capillary density in ischemic hindlimbs were significantly improved in human VPC-derived EC-transplanted mice, compared to human peripheral and umbilical cord blood-derived endothelial progenitor cells (pEPC and uEPC) transplanted mice. The combined transplantation of human VPC-derived EC and MC synergistically improved blood flow of ischemic hindlimbs remarkably, compared to the single cell transplantations. Transplanted VPC-derived vascular cells were effectively incorporated into host circulating vessels as EC and MC to maintain long-term vascular integrity. CONCLUSIONS: Our findings suggest that the combined transplantation of human ES cells-derived EC and MC can be used as a new promising strategy for therapeutic vascular regeneration in patients with tissue ischemia

    Current tidal power technologies and their suitability for applications in coastal and marine areas

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    A considerable body of research is currently being performed to quantify available tidal energy resources and to develop efficient devices with which to harness them. This work is naturally focussed on maximising power generation from the most promising sites, and a review of the literature suggests that the potential for smaller scale, local tidal power generation from shallow near-shore sites has not yet been investigated. If such generation is feasible, it could have the potential to provide sustainable electricity for nearby coastal homes and communities as part of a distributed generation strategy, and would benefit from easier installation and maintenance, lower cabling and infrastructure requirements and reduced capital costs when compared with larger scale projects. This article reviews tidal barrages and lagoons, tidal turbines, oscillating hydrofoils and tidal kites to assess their suitability for small-scale electricity generation in shallow waters. This is achieved by discussing the power density, scalability, durability, maintainability, economic potential and environmental impacts of each concept. The performance of each technology in each criterion is scored against axial-flow turbines, allowing for them to be ranked according to their overall suitability. The review suggests that tidal kites and range devices are not suitable for small-scale shallow water applications due to depth and size requirements respectively. Cross-flow turbines appear to be the most suitable technology, as they have high power densities and a maximum size that is not constrained by water depth

    Effect of hypoxia and Beraprost sodium on human pulmonary arterial smooth muscle cell proliferation: the role of p27kip1

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    <p>Abstract</p> <p>Background</p> <p>Hypoxia induces the proliferation of pulmonary arterial smooth muscle cell (PASMC) <it>in vivo </it>and <it>in vitro</it>, and prostacyclin analogues are thought to inhibit the growth of PASMC. Previous studies suggest that p27<sup>kip1</sup>, a kind of cyclin-dependent kinase inhibitor, play an important role in the smooth muscle cell proliferation. However, the mechanism of hypoxia and the subcellular interactions between p27<sup>kip1 </sup>and prostacyclin analogues in human pulmonary arterial smooth muscle cell (HPASMC) are not fully understood.</p> <p>Methods</p> <p>We investigated the role of p27<sup>kip1 </sup>in the ability of Beraprost sodium (BPS; a stable prostacyclin analogue) to inhibit the proliferation of HPASMC during hypoxia. To clarify the biological effects of hypoxic air exposure and BPS on HPASMC, the cells were cultured in a hypoxic chamber under various oxygen concentrations (0.1–21%). Thereafter, DNA synthesis was measured as bromodeoxyuridine (BrdU) incorporation, the cell cycle was analyzed by flow cytometry with propidium iodide staining. The p27<sup>kip1 </sup>mRNA and protein expression and it's stability was measured by real-time RT-PCR and Western blotting. Further, we assessed the role of p27<sup>kip1 </sup>in HPASMC proliferation using p27<sup>kip1 </sup>gene knockdown using small interfering RNA (siRNA) transfection.</p> <p>Results</p> <p>Although severe hypoxia (0.1% oxygen) suppressed the proliferation of serum-stimulated HPASMC, moderate hypoxia (2% oxygen) enhanced proliferation in accordance with enhanced p27<sup>kip1 </sup>protein degradation, whereas BPS suppressed HPASMC proliferation under both hypoxic and normoxic conditions by suppressing p27<sup>kip1 </sup>degradation with intracellular cAMP-elevation. The 8-bromo-cyclic adenosine monophosphate (8-Br-cAMP), a cAMP analogue, had similar action as BPS in the regulation of p27<sup>kip1</sup>. Moderate hypoxia did not affect the stability of p27<sup>kip1 </sup>protein expression, but PDGF, known as major hypoxia-induced growth factors, significantly decreased p27<sup>kip1 </sup>protein stability. We also demonstrated that BPS and 8-Br-cAMP suppressed HPASMC proliferation under both hypoxic and normoxic conditions by blocking p27<sup>kip1 </sup>mRNA degradation. Furthermore, p27<sup>kip1 </sup>gene silencing partially attenuated the effects of BPS and partially restored hypoxia-induced proliferation.</p> <p>Conclusion</p> <p>Our study suggests that moderate hypoxia induces HPASMC proliferation, which is partially dependent of p27<sup>kip1 </sup>down-regulation probably <it>via </it>the induction of growth factors such as PDGF, and BPS inhibits both the cell proliferation and p27<sup>kip1 </sup>mRNA degradation through cAMP pathway.</p

    Interaction with potential donors' families: The professionals' community of concern—a phenomenological study

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    The aim of this paper was to explore the health professionals' experiences and gain a deeper understanding of interaction with families of critically ill or traumatized patients with severe brain injuries. The methodological approach was qualitative and phenomenological. Data were collected through participant observation and in-depth interviews with nurses, physicians, and chaplains working in two ICUs in a Norwegian university hospital. A thematic analysis was used for analyzing data. Two main themes emerged from analysis: Patient oriented even when present and Family oriented even when absent. Each main theme is divided into two sub-themes. The themes appeared as phases in an interaction process. In the two first phases the interaction may be characterized as Alternating between being absent and present and Following up and withholding information and in the two last phases as Turning point and changing focus and Partly present when waiting for death. The findings are in the discussion illuminated by the phenomenological concept of concern. Concern is visible as care, and the distinction in care between “leaps in” and “leaps ahead” and “ready-to-hand” and “unready-to-hand” are topics in the discussion. Because of the complexity of caring for both patient and family, the situation demands efforts to relieve nurses in particular, during the most demanding phases of the process

    Multiple Mating and Family Structure of the Western Tent Caterpillar, Malacosoma californicum pluviale: Impact on Disease Resistance

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    Background Levels of genetic diversity can strongly influence the dynamics and evolutionary changes of natural populations. Survival and disease resistance have been linked to levels of genetic diversity in eusocial insects, yet these relationships remain untested in gregarious insects where disease transmission can be high and selection for resistance is likely to be strong. Methodology/Principal Findings Here we use 8 microsatellite loci to examine genetic variation in 12 families of western tent caterpillars, Malacosoma californicum pluviale from four different island populations to determine the relationship of genetic variability to survival and disease resistance. In addition these genetic markers were used to elucidate the population structure of western tent caterpillars. Multiple paternity was revealed by microsatellite markers, with the number of sires estimated to range from one to three per family (mean ± SE = 1.92±0.23). Observed heterozygosity (HO) of families was not associated to the resistance of families to a nucleopolyhedrovirus (NPV) (r = 0.161, F1,12 = 0.271, P = 0.614), a major cause of mortality in high-density populations, but was positively associated with larval survival (r = 0.635, F1,10 = 5.412, P = 0.048). Genetic differentiation among the families was high (FST = 0.269, P&lt;0.0001), and families from the same island were as differentiated as were families from other islands. Conclusion/Significance We have been able to describe and characterize 8 microsatellite loci, which demonstrate patterns of variation within and between families of western tent caterpillars. We have discovered an association between larval survival and family-level heterozygosity that may be relevant to the population dynamics of this cyclic forest lepidopteran, and this will be the topic of future work
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