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991.
María Carmen Balo Jos Brea Olga Caamao Franco Fernndez Xerardo García-Mera Carmen Lpez María Isabel Loza María Isabel Nieto Jos Enrique Rodríguez-Borges 《Bioorganic & medicinal chemistry》2009,17(18):6755-6760
The synthesis of an important set of 3-furfurylxanthine derivatives is described. Binding affinities were determined for rat A1 and human A2A, A2B and A3 receptors. Several of the 3-furfuryl-7-methylxanthine derivatives showed moderate-to-high affinity at human A2B receptors, the most active compound (10d) having a Ki of 7.4 nM for hA2B receptors, with selectivities over rA1 and hA2A receptors up to 14-fold and 11-fold, respectively. Affinities for hA3 receptors were very low for all members of the set. 相似文献
992.
The PSO family: deduction, stochastic analysis and comparison 总被引:2,自引:0,他引:2
The PSO algorithm can be physically interpreted as a stochastic damped mass-spring system: the so-called PSO continuous model.
Furthermore, PSO corresponds to a particular discretization of the PSO continuous model. In this paper, we introduce a delayed
version of the PSO continuous model, where the center of attraction might be delayed with respect to the particle trajectories.
Based on this mechanical analogy, we derive a family of PSO versions. For each member of this family, we deduce the first
and second order stability regions and the corresponding spectral radius. As expected, the PSO-family algorithms approach
the PSO continuous model (damped-mass-spring system) as the size of the time step goes to zero. All the family members are
linearly isomorphic when they are derived using the same delay parameter. If the delay parameter is different, the algorithms
have corresponding stability regions of any order, but they differ in their respective force terms. All the PSO versions perform
fairly well in a very broad area of the parameter space (inertia weight and local and global accelerations) that is close
to the border of the second order stability regions and also to the median lines of the first order stability regions where
no temporal correlation between trajectories exists. In addition, these regions are fairly similar for different benchmark
functions. When the number of parameters of the cost function increases, these regions move towards higher inertia weight
values (w=1) and lower total mean accelerations where the temporal covariance between trajectories is positive. Finally, the comparison
between different PSO versions results in the conclusion that the centered version (CC-PSO) and PSO have the best convergence
rates. Conversely, the centered-progressive version (CP-PSO) has the greatest exploratory capabilities. These features have
to do with the way these algorithms update the velocities and positions of particles in the swarm. Knowledge of their respective
dynamics can be used to propose a family of simple and stable algorithms, including hybrid versions. 相似文献
993.
Inspired by the dynamic clamp of cellular neuroscience, this paper introduces VPI—Virtual Partner Interaction—a coupled dynamical system for studying real time interaction between a human and a machine. In this proof of concept study, human subjects coordinate hand movements with a virtual partner, an avatar of a hand whose movements are driven by a computerized version of the Haken-Kelso-Bunz (HKB) equations that have been shown to govern basic forms of human coordination. As a surrogate system for human social coordination, VPI allows one to examine regions of the parameter space not typically explored during live interactions. A number of novel behaviors never previously observed are uncovered and accounted for. Having its basis in an empirically derived theory of human coordination, VPI offers a principled approach to human-machine interaction and opens up new ways to understand how humans interact with human-like machines including identification of underlying neural mechanisms. 相似文献
994.
Edward Mlaga-Trillo Gonzalo P Solis Yvonne Schrock Corinna Geiss Lydia Luncz Venus Thomanetz Claudia A. O Stuermer 《PLoS biology》2009,7(3)
Prion proteins (PrPs) are key players in fatal neurodegenerative disorders, yet their physiological functions remain unclear, as PrP knockout mice develop rather normally. We report a strong PrP loss-of-function phenotype in zebrafish embryos, characterized by the loss of embryonic cell adhesion and arrested gastrulation. Zebrafish and mouse PrP mRNAs can partially rescue this knockdown phenotype, indicating conserved PrP functions. Using zebrafish, mouse, and Drosophila cells, we show that PrP: (1) mediates Ca+2-independent homophilic cell adhesion and signaling; and (2) modulates Ca+2-dependent cell adhesion by regulating the delivery of E-cadherin to the plasma membrane. In vivo time-lapse analyses reveal that the arrested gastrulation in PrP knockdown embryos is due to deficient morphogenetic cell movements, which rely on E-cadherin–based adhesion. Cell-transplantation experiments indicate that the regulation of embryonic cell adhesion by PrP is cell-autonomous. Moreover, we find that the local accumulation of PrP at cell contact sites is concomitant with the activation of Src-related kinases, the recruitment of reggie/flotillin microdomains, and the reorganization of the actin cytoskeleton, consistent with a role of PrP in the modulation of cell adhesion via signaling. Altogether, our data uncover evolutionarily conserved roles of PrP in cell communication, which ultimately impinge on the stability of adherens cell junctions during embryonic development. 相似文献
995.
G. van Soest T. P. M. Goderie N. Gonzalo S. Koljenović G. L. J. H. van Leenders E. Regar P. W. Serruys A. F. W. van der Steen 《Netherlands heart journal》2009,17(11):448-450
Optical coherence tomography (OCT) allows highly accurate diagnosis of atherosclerotic plaques, including measurement of the thickness of fibrous caps, permitting an assessment of the risk of rupture. While the OCT image presents morphological information in highly resolved detail, it relies on interpretation by trained readers for the identification of tissue type. We developed a method for quantitative classification of atherosclerotic plaque constituents. The optical attenuation coefficient μt distinguishes different tissue types: necrotic core and macrophage infiltration exhibit strong attenuation, μt≥10 mm−1, while calcific and fibrous tissue have a lower μt≈2–5 mm−1. (Neth Heart J 2009;17:448-50.) 相似文献
996.
Mónica López-Peña Nuria Alemañ Fernando Muñoz Dolors Fondevila María Luisa Suárez Ana Goicoa Jose María Nieto 《Acta veterinaria Scandinavica》2009,51(1):20
A dog presented with cutaneous nodules, enlarged lymph nodes and oedema in limbs, face and abdomen. The diagnosis of visceral
leishmaniasis was established by identification of Leishmania amastigotes within macrophages from skin and popliteal lymph node biopsies. At necropsy, lesions were found in different
organs, but it was particularly striking to observe large areas of pallor in the myocardium. Histological examination revealed
an intense chronic inflammatory reaction in many organs, and numerous macrophages were found to contain amastigote forms of
Leishmania. The inflammatory reaction was especially severe in the heart, where large areas of the myocardium appeared infiltrated with
huge numbers of mononuclear immune cells, causing cardiac muscle atrophy and degeneration. Despite the severe inflammation,
the number of parasitized macrophages was low in the myocardium, as revealed by immunohistochemical staining of Leishmania amastigotes. Because cardiac involvement is not usually described in this condition, this dog represents a very rare case
of canine visceral leishmaniasis with affection of the myocardium. 相似文献
997.
998.
Differential effects of exposure to parasites and bacteria on stress response in turbot Scophthalmus maximus simultaneously stressed by low water depth 下载免费PDF全文
J. J. Rodríguez‐Quiroga C. Otero‐Rodiño P. Suárez T. P. Nieto J. M. García Estévez F. San Juan J. L. Soengas 《Journal of fish biology》2017,91(1):242-259
The stress response of turbot Scophthalmus maximus was evaluated in fish maintained 8 days under different water depths, normal (NWD, 30 cm depth, total water volume 40 l) or low (LWD, 5 cm depth, total water volume 10 l), in the additional presence of infection–infestation of two pathogens of this species. This was caused by intraperitoneal injection of sublethal doses of the bacterium Aeromonas salmonicida subsp. salmonicida or the parasite Philasterides dicentrarchi (Ciliophora:Scuticociliatida). The LWD conditions were stressful for fish, causing increased levels of cortisol in plasma, decreased levels of glycogen in liver and nicotinamide adenine dinucleotide phosphate (NADP) and increased activities of G6Pase and GSase. The presence of bacteria or parasites in fish under NWD resulted in increased cortisol levels in plasma whereas in liver, changes were of minor importance including decreased levels of lactate and GSase activity. The simultaneous presence of bacteria and parasites in fish under NWD resulted a sharp increase in the levels of cortisol in plasma and decreased levels of glucose. Decreased levels of glycogen and lactate and activities of GSase and glutathione reductase (GR), as well as increased activities of glucose‐6‐phosphate dehydrogenase (G6PDH), 6‐phosphogluconate dehydrogenase (6PGDH) and levels of nicotinamide adenine dinucleotide phosphate (NADPH) occurred in the same fish in liver. Finally, the presence of pathogens in S. maximus under stressful conditions elicited by LWD resulted in synergistic actions of both type of stressors in cortisol levels. In liver, the presence of bacteria or parasites induced a synergistic action on several variables such as decreased activities of G6Pase and GSase as well as increased levels of NADP and NADPH and increased activities of GPase, G6PDH and 6PGDH. 相似文献
999.
Carcinogen susceptibility is regulated by genome architecture and predicts cancer mutagenesis 下载免费PDF全文
Pablo E García‐Nieto Erin K Schwartz Devin A King Jonas Paulsen Philippe Collas Rafael E Herrera Ashby J Morrison 《The EMBO journal》2017,36(19):2829-2843
The development of many sporadic cancers is directly initiated by carcinogen exposure. Carcinogens induce malignancies by creating DNA lesions (i.e., adducts) that can result in mutations if left unrepaired. Despite this knowledge, there has been remarkably little investigation into the regulation of susceptibility to acquire DNA lesions. In this study, we present the first quantitative human genome‐wide map of DNA lesions induced by ultraviolet (UV) radiation, the ubiquitous carcinogen in sunlight that causes skin cancer. Remarkably, the pattern of carcinogen susceptibility across the genome of primary cells significantly reflects mutation frequency in malignant melanoma. Surprisingly, DNase‐accessible euchromatin is protected from UV, while lamina‐associated heterochromatin at the nuclear periphery is vulnerable. Many cancer driver genes have an intrinsic increase in carcinogen susceptibility, including the BRAF oncogene that has the highest mutation frequency in melanoma. These findings provide a genome‐wide snapshot of DNA injuries at the earliest stage of carcinogenesis. Furthermore, they identify carcinogen susceptibility as an origin of genome instability that is regulated by nuclear architecture and mirrors mutagenesis in cancer. 相似文献
1000.
Unraveling cryptic invasion of a freshwater snail in Chile based on molecular and morphological data
Gonzalo A. Collado 《Biodiversity and Conservation》2017,26(3):567-578
Cryptic species may cause biological invasions to be overlooked leading to underestimation of the potential impacts of invaders on the new ecosystems. Identification of freshwater snails is challenging because of the scarcity of discriminative morphological characters and the limited taxonomic knowledge of some taxa. Here, molecular and morphological analyses were performed to investigate the identity of viable populations of the genus Physa in aquatic ecosystems of different basins in northern and central Chile, including habitats where the native species Physa chilensis and Physa nodulosa have been traditionally recognized. Molecular analyses based on mitochondrial DNA sequences from the small subunit 16S rDNA and cytochrome c oxidase subunit 1 identified all specimens sequenced as belonging to the globally invasive species Physa acuta. Microscopic examination of the radula and morphological observations of the reproductive system were congruent with these findings. Highly divergent haplotypes found in El Salto suggest multiple introductions of different lineages of the invader in this locality. It is clear that for future management planning a more reliable assessment of the status of P. chilensis and P. nodulosa is required. 相似文献