427 research outputs found

    Apparent Fractality Emerging from Models of Random Distributions

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    The fractal properties of models of randomly placed nn-dimensional spheres (nn=1,2,3) are studied using standard techniques for calculating fractal dimensions in empirical data (the box counting and Minkowski-sausage techniques). Using analytical and numerical calculations it is shown that in the regime of low volume fraction occupied by the spheres, apparent fractal behavior is observed for a range of scales between physically relevant cut-offs. The width of this range, typically spanning between one and two orders of magnitude, is in very good agreement with the typical range observed in experimental measurements of fractals. The dimensions are not universal and depend on density. These observations are applicable to spatial, temporal and spectral random structures. Polydispersivity in sphere radii and impenetrability of the spheres (resulting in short range correlations) are also introduced and are found to have little effect on the scaling properties. We thus propose that apparent fractal behavior observed experimentally over a limited range may often have its origin in underlying randomness.Comment: 19 pages, 12 figures. More info available at http://www.fh.huji.ac.il/~dani

    Arylmethylamino steroids as antiparasitic agents

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    In search of antiparasitic agents, we here identify arylmethylamino steroids as potent compounds and characterize more than 60 derivatives. The lead compound 1o is fast acting and highly active against intraerythrocytic stages of chloroquine-sensitive and resistant Plasmodium falciparum parasites (IC50 1–5?nM) as well as against gametocytes. In P. berghei-infected mice, oral administration of 1o drastically reduces parasitaemia and cures the animals. Furthermore, 1o efficiently blocks parasite transmission from mice to mosquitoes. The steroid compounds show low cytotoxicity in mammalian cells and do not induce acute toxicity symptoms in mice. Moreover, 1o has a remarkable activity against the blood-feeding trematode parasite Schistosoma mansoni. The steroid and the hydroxyarylmethylamino moieties are essential for antimalarial activity supporting a chelate-based quinone methide mechanism involving metal or haem bioactivation. This study identifies chemical scaffolds that are rapidly internalized into blood-feeding parasites

    Thermo-mechanical analysis of dental silicone polymers

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    Soft lining materials are used to replace the inner surface of a conventional complete denture, especially for weak elderly patients, with delicate health who cannot tolerate the hard acrylic denture base. Most of these patients have fragile supporting mucosa, excessive residual ridge resorption, particularly on the mandibular arch. The application of a soft liner to the mandibular denture allows absorbing impact forces during mastication and relieving oral mucosa. Actually, the silicone rubbers constitute the main family of commercialised soft lining materials. This study was conducted to understand the relationships between the mechanical properties and the physical structure of polysiloxanes. For this purpose, a series of polysiloxanes of various chemical compositions have been investigated. The evolution of their physical structure as a function of temperature has been followed by differential scanning calorimetry (DSC). In order to facilitate comparisons, the mechanical modulus has been analysed upon the same heating rate using dynamic mechanical analysis (DMA). Polysiloxanes actually commercialised as soft denture liners are three-dimensional networks: the flexibility of chains allows a crystalline organisation in an amorphous phase leading to the low value of the shear modulus. The dynamic mechanical analysis shows that they are used in the rubbery state. So, polysiloxanes have steady mechanical properties during physiological utilisation

    The interaction between a sexually transferred steroid hormone and a female protein regulates oogenesis in the malaria mosquito anopheles gambiae

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    Molecular interactions between male and female factors during mating profoundly affect the reproductive behavior and physiology of female insects. In natural populations of the malaria mosquito Anopheles gambiae, blood-fed females direct nutritional resources towards oogenesis only when inseminated. Here we show that the mating-dependent pathway of egg development in these mosquitoes is regulated by the interaction between the steroid hormone 20-hydroxy-ecdysone (20E) transferred by males during copulation and a female Mating-Induced Stimulator of Oogenesis (MISO) protein. RNAi silencing of MISO abolishes the increase in oogenesis caused by mating in blood-fed females, causes a delay in oocyte development, and impairs the function of male-transferred 20E. Co-immunoprecipitation experiments show that MISO and 20E interact in the female reproductive tract. Moreover MISO expression after mating is induced by 20E via the Ecdysone Receptor, demonstrating a close cooperation between the two factors. Male-transferred 20E therefore acts as a mating signal that females translate into an increased investment in egg development via a MISO-dependent pathway. The identification of this male–female reproductive interaction offers novel opportunities for the control of mosquito populations that transmit malaria

    Scaling Law for a Magnetic Impurity Model with Two-Body Hybridization

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    We consider a magnetic impurity coupled to the hybridizing and screening channels of a conduction band. The model is solved in the framework of poor man's scaling and Cardy's generalized theories. We point out that it is important to include a two-body hybridization if the scaling theory is to be valid for the band width larger than UU. We map out the boundary of the Fermi-non-Fermi liquid phase transition as a function of the model parameters.Comment: 14 pages, latex, 1 figure included

    Quantitative plane-resolved crystal growth and dissolution kinetics by coupling in situ optical microscopy and diffusion models : the case of salicylic acid in aqueous solution

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    The growth and dissolution kinetics of salicylic acid crystals are investigated in situ by focusing on individual microscale crystals. From a combination of optical microscopy and finite element method (FEM) modeling, it was possible to obtain a detailed quantitative picture of dissolution and growth dynamics for individual crystal faces. The approach uses real-time in situ growth and dissolution data (crystal size and shape as a function of time) to parametrize a FEM model incorporating surface kinetics and bulk to surface diffusion, from which concentration distributions and fluxes are obtained directly. It was found that the (001) face showed strong mass transport (diffusion) controlled behavior with an average surface concentration close to the solubility value during growth and dissolution over a wide range of bulk saturation levels. The (1̅10) and (110) faces exhibited mixed mass transport/surface controlled behavior, but with a strong diffusive component. As crystals became relatively large, they tended to exhibit peculiar hollow structures in the end (001) face, observed by interferometry and optical microscopy. Such features have been reported in a number of crystals, but there has not been a satisfactory explanation for their origin. The mass transport simulations indicate that there is a large difference in flux across the crystal surface, with high values at the edge of the (001) face compared to the center, and this flux has to be redistributed across the (001) surface. As the crystal grows, the redistribution process evidently can not be maintained so that the edges grow at the expense of the center, ultimately creating high index internal structures. At later times, we postulate that these high energy faces, starved of material from solution, dissolve and the extra flux of salicylic acid causes the voids to close

    A Re-Annotation of the Saccharomyces Cerevisiae Genome

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    Discrepancies in gene and orphan number indicated by previous analyses suggest that S. cerevisiae would benefit from a consistent re-annotation. In this analysis three new genes are identified and 46 alterations to gene coordinates are described. 370 ORFs are defined as totally spurious ORFs which should be disregarded. At least a further 193 genes could be described as very hypothetical, based on a number of criteria. It was found that disparate genes with sequence overlaps over ten amino acids (especially at the N-terminus) are rare in both S. cerevisiae and Sz. pombe. A new S. cerevisiae gene number estimate with an upper limit of 5804 is proposed, but after the removal of very hypothetical genes and pseudogenes this is reduced to 5570. Although this is likely to be closer to the true upper limit, it is still predicted to be an overestimate of gene number. A complete list of revised gene coordinates is available from the Sanger Centre (S. cerevisiae reannotation: ftp://ftp/pub/yeast/SCreannotation)

    Hypoxic Environment and Paired Hierarchical 3D and 2D Models of Pediatric H3.3-Mutated Gliomas Recreate the Patient Tumor Complexity.

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    BACKGROUND:Pediatric high-grade gliomas (pHGGs) are facing a very dismal prognosis and representative pre-clinical models are needed for new treatment strategies. Here, we examined the relevance of collecting functional, genomic, and metabolomics data to validate patient-derived models in a hypoxic microenvironment. METHODS:From our biobank of pediatric brain tumor-derived models, we selected 11 pHGGs driven by the histone H3.3K28M mutation. We compared the features of four patient tumors to their paired cell lines and mouse xenografts using NGS (next generation sequencing), aCGH (array comparative genomic hybridization), RNA sequencing, WES (whole exome sequencing), immunocytochemistry, and HRMAS (high resolution magic angle spinning) spectroscopy. We developed a multicellular in vitro model of cell migration to mimic the brain hypoxic microenvironment. The live cell technology Incucyte© was used to assess drug responsiveness in variable oxygen conditions. RESULTS:The concurrent 2D and 3D cultures generated from the same tumor sample exhibited divergent but complementary features, recreating the patient intra-tumor complexity. Genomic and metabolomic data described the metabolic changes during pHGG progression and supported hypoxia as an important key to preserve the tumor metabolism in vitro and cell dissemination present in patients. The neurosphere features preserved tumor development and sensitivity to treatment. CONCLUSION:We proposed a novel multistep work for the development and validation of patient-derived models, considering the immature and differentiated content and the tumor microenvironment of pHGGs
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