9 research outputs found

    An RBF-based reparameterization method for constrained texture mapping

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    Texture mapping has long been used in computer graphics to enhance the realism of virtual scenes. However, to match the 3D model feature points with the corresponding pixels in a texture image, surface parameterization must satisfy specific positional constraints. However, despite numerous research efforts, the construction of a mathematically robust, foldover‐free parameterization that is subject to positional constraints continues to be a challenge. In the present paper, this foldover problem is addressed by developing radial basis function (RBF) based reparameterization. Given initial 2D embedding of a 3D surface, the proposed method can reparameterize 2D embedding into a foldover ‐free 2D mesh, satisfying a set of user‐specified constraint points. In addition, this approach is mesh‐free. Therefore, generating smooth texture mapping results is possible without extra smoothing optimization

    In silico tumor-targeting technologies for the evasion of acidity-induced multidrug resistance

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    The physiology of tumors is tied to MDR mechanisms that hamper chemotherapeutic effects, particularly passive membrane crossing compounds, like hydrophobic Lewis base drugs. Although the lysosomal entrapment phenomena remains to be fully understood, this pH-dependent MDR mechanism induces drug sequestration in the acidic lysosomal lumen. Overcoming the MDR requires multi-pronged therapies, which often overlook an ubiquitous tumor trait: the extracellular acidity of the tumor microenvironment (TME). To address this, pHLIP peptides have emerged as an acidity-selective technology for tumor-targeting drug delivery. We focused on refining our protocols with enhanced sampling techniques and tumor-like features to improve the predictive abilities of the CpHMD-L methodology and augment the realism of these biomolecular models, thus bridging the gap to in vivo and cellular conditions. The optimized protocol coupled the CpHMD-L method with a pHRE scheme, providing a robust baseline. Then, we applied the protocol to study the diverging therapeutic efficiency of the wt and an over-performing Var3 peptide. A novel implementation of a pH gradient CpHMD-L method successfully reproduced experimental performances, thus elucidating pivotal residues electrostatic networks that dictate peptides thermodynamic stability in TME conditions. A multi-peptide study highlighted the remarkable effects of permuting arginines in modulating the local vicinity of key aspartates. These findings heavily correlate with their tumor-targeting performance, supporting more rational and in silico-based approaches to peptide design. Finally, the pH-dependent mechanism of lysosomal entrapment was modelled, hinting at the important role of acidity in Lewis base drugs membrane intercalation. Additional pH-dependent permeability calculations, using a novel US-CpHMD method, identified the TME acidity as an additional MDR defense mechanism that impairs clinical efficiency. It also revealed an intrinsic flaw of these compounds, since they preferably target healthy cells. These findings have important implications in rational drug design, especially of conjugated therapies with pHLIP-like drug delivery systems to overcome these challenges

    Untangling hotel industry’s inefficiency: An SFA approach applied to a renowned Portuguese hotel chain

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    The present paper explores the technical efficiency of four hotels from Teixeira Duarte Group - a renowned Portuguese hotel chain. An efficiency ranking is established from these four hotel units located in Portugal using Stochastic Frontier Analysis. This methodology allows to discriminate between measurement error and systematic inefficiencies in the estimation process enabling to investigate the main inefficiency causes. Several suggestions concerning efficiency improvement are undertaken for each hotel studied.info:eu-repo/semantics/publishedVersio

    Reduction in mesenchymal stem cell numbers in premature aging DNA repair deficient TTD mice

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    Background: Mice carrying mutations in DNA repair genes often show signs of accelerated ageing and therefore can be used as a model system to study age related diseases like osteoporosis. It has been shown that TTD mice, carrying a mutation in the nucleotide excision repair gene XPD (xeroderma pigmentosa group D), display features of ageing related osteoporosis as well as adipose tissue hypoplasia. Since both cell types involved, osteoblasts as well as adipocytes, arise from the same mesenchymal stem cell population, the aim of the current project was to study the number, proliferation and differentiation potential of these cells in TTD compared to wild type (WT) mice. This might provide us with useful information concerning the mechanism behind age-related osteoporosis and the loss of adipose tissue.Methods: Bone marrow from old TTD and WT mice was cultured under osteogenic or adipogenic conditions and analysed for alkaline phosphatase activity (ALP), mineralisation (osteoblast) and lipid deposition (adipocyte).Results: Under osteogenic conditions the number of ALP-positive colonies after 9 and 14 days of culture was significantly decreased (p=0.02) in TTD compared to WT mice. The rate at which new ALP-positive colonies are formed between day 9 and day 14 of culture has not changed between TTD and WT mice, indicating that the decrease in colony number is not due to a delay in differentiation. Mineralisation of ALP-positive colonies did not seem to be affected, with a borderline significant decrease on day 14 at the onset of mineralisation but no significant changes on day 21 of culture. Lipid deposition was strongly reduced in TTD compared to WT mice (p=0.01) after 35 days of culture.Conclusions: The observed reduction in osteoblast and adipocyte differentiation indicates a reduction of mesenchymal stem cell numbers in TTD mice. This reduction in mesenchymal stem cell numbers and the corresponding decline in osteoblast differentiation could explain the premature osteoporotic features observed in TTD mice. In line with this, the reduction of mesenchymal stem cells and adipocyte differentiation may underlie the adipose tissue hypoplasia observed in TTD mice

    Deletion of the ghrelin receptor GHSR corrects the trabecular, but not the cortical bone changes in the femoral head of ob/ob mice

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    Background: There exists an intriguing and complex relationship between fat and bone cells with respect to aging and osteoporosis, which is mediated in part by leptin. Genetically obese mice (ob/ob), that lack leptin, have aheterogeneous bone phenotype, with differential effects on cortical and trabecular compartments. Besides its role in bone metabolism, leptin is most well known for its anorexigenic properties. Opposed in action to leptin is ghrelin, a potent orexigenic peptide hormone derived from the stomach. Ghrelin and leptin also act as each other’s antagonists in gonadal and immune system function.Objective: To determine if ghrelin opposes leptin action on bone metabolism.Methods: Characterization of femoral micro-architecture in 6 months old male wild type, ob/ob, ghrelin receptor knockout (Ghsr -/-), and ob/ob.Ghsr-/- mice using micro-computed tomography.Results: Deletion of Ghsr alone did not significantly alter bone micro-architecture in wild type mice. Deletion of leptin reduced cortical volume and thickness in the femoral head of wild type mice, while it increased endocortical volume. Tissue volume remained unaffected. Conversely, deletion of leptin increased trabecular bone volume, trabecular number and connectivity in wild type mice. Additional deletion of Ghsr in ob/ob mice restored the changes to wild type levels in trabecular bone, but not in cortical bone (all not significant).Conclusion: We found that leptin deficiency has a negative effect on cortical and a positive effect on trabecular bone micro-architecture, confirming the heterogeneous skeletal effects observed by others in ob/ob mice. Knocking out ghrelin signaling compensates for the effect of leptin deficiency on trabecular bone. These observations demonstrate the positive activity of ghrelin signaling in bone, and suggest that ghrelin and leptin have opposing actions on bone metabolism

    Remote Sensing of Earth Resources: A literature survey with indexes (1970 - 1973 supplement). Section 1: Abstracts

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    Abstracts of reports, articles, and other documents introduced into the NASA scientific and technical information system between March 1970 and December 1973 are presented in the following areas: agriculture and forestry, environmental changes and cultural resources, geodesy and cartography, geology and mineral resources, oceanography and marine resources, hydrology and water management, data processing and distribution systems, instrumentation and sensors, and economic analysis
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