646 research outputs found

    A (2n+1)-dimensional quantum group constructed from a skew-symmetric matrix

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    Beginning with a skew-symmetric matrix, we define a certain Poisson--Lie group. Its Poisson bracket can be viewed as a cocycle perturbation of the linear (or "Lie-Poisson") Poisson bracket. By analyzing this Poisson structure, we gather enough information to construct a C*-algebraic locally compact quantum group, via the "cocycle bicrossed product construction" method. The quantum group thus obtained is shown to be a deformation quantization of the Poisson-Lie group, in the sense of Rieffel

    Modeling DNA Structure, Elasticity and Deformations at the Base-pair Level

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    We present a generic model for DNA at the base-pair level. We use a variant of the Gay-Berne potential to represent the stacking energy between neighboring base-pairs. The sugar-phosphate backbones are taken into account by semi-rigid harmonic springs with a non-zero spring length. The competition of these two interactions and the introduction of a simple geometrical constraint leads to a stacked right-handed B-DNA-like conformation. The mapping of the presented model to the Marko-Siggia and the Stack-of-Plates model enables us to optimize the free model parameters so as to reproduce the experimentally known observables such as persistence lengths, mean and mean squared base-pair step parameters. For the optimized model parameters we measured the critical force where the transition from B- to S-DNA occurs to be approximately 140pN140{pN}. We observe an overstretched S-DNA conformation with highly inclined bases that partially preserves the stacking of successive base-pairs.Comment: 15 pages, 25 figures. submitted to PR

    WNT signalling in prostate cancer

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    Genome sequencing and gene expression analyses of prostate tumours have highlighted the potential importance of genetic and epigenetic changes observed in WNT signalling pathway components in prostate tumours-particularly in the development of castration-resistant prostate cancer. WNT signalling is also important in the prostate tumour microenvironment, in which WNT proteins secreted by the tumour stroma promote resistance to therapy, and in prostate cancer stem or progenitor cells, in which WNT-β-catenin signals promote self-renewal or expansion. Preclinical studies have demonstrated the potential of inhibitors that target WNT receptor complexes at the cell membrane or that block the interaction of β-catenin with lymphoid enhancer-binding factor 1 and the androgen receptor, in preventing prostate cancer progression. Some WNT signalling inhibitors are in phase I trials, but they have yet to be tested in patients with prostate cancer

    Efeito de diferentes manejos de fornecimento prolongado de colostro sobre os níveis de proteína e albúmina séricas e desempenho de bezerras recém-nascidas

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    The serum total protein and albumin concentrations and the performance under different milk feeding programs were evaluated in twenty-four female Holstein newborn calves, randomly allocated in three treatments. The animals were daily fed milk or supplemental colostrum, in different feeding programs during the first thirty days of Ufe. Blood samples were collected at 3; 5;10; 15; 17; 20; 22; 25; 30; 40; 50 and 60 days of age and analysed for serum total protein and serum albumin. Animals were weighed at 0; 5; 10; 15; 20; 25; 30; 40; 50 and 60 days after birth. In the first sixty days, the serum total protein concentration in treatment 3 (colostrum fed twice a day) was higher (p < 0.05) than in treatment 1 (milk). The concentration of serum was also different at different ages (p < 0.0001). During the experimental period the total protein decreased (equation r² = 0.98). Serum albumin levels were similar at all ages, but different in treatments. Treatment 2 (colostrum fed once a day) levels were higher (p < 0.05) than in treatment 1 for serum albumin. Treatment 3 body weight gain was higher (p < 0.05) than in treatment 1 during the experimental period. It was concluded that the best performance was found in calves that received a supplemental colostrum diet twice a day.Os níveis séricos de proteína total e albúmina e o desempenho de bezerras holandesas foram estudados utilizando-se 24 animais recém-nascidos em um delineamento experimental inteiramente ao acaso em parcelas subdivididas, com três tratamentos à base de leite e colostro suplementar, a saber: tratamento 1 - colostro materno no 1&deg; dia de vida (idem para tratamentos 2 e 3) e 2 litros de leite pela manhã e 2 litros de leite à tarde, do 2&deg; dia de vida até o 30&deg; dia de vida; tratamento 2 - fornecimento de 0,8 litros de leite + 1,2 litros de colostro pela manhã e 2 litros de leite à tarde, até 30 dias de idade; tratamento 3 - fornecimento de 1,4 litros de leite + 0,6 litros de colostro pela manhã e igual dieta à tarde, até 30 dias de idade. Amostras de sangue foram coletadas aos 3, 5, 10, 15,17, 20, 22, 25, 30, 40, 50 e 60 dias de vida e analisadas quanto à concentração de proteína total e albúmina séricas.Os animais foram pesados ao nascer e aos 5, 10, 15, 20, 25, 30, 40, 50 e 60 dias de idade. Os animais do tratamento 3 (colostro duas vezes/dia) tiveram concentração de proteína total sérica superior (p < 0,05) a dos animais do tratamento 1(leite). O nível sérico de proteína total variou entre idades experimentais (p < 0,0001). Houve redução da concentração de proteína total durante o período experimental (r² = 0,98). A albúmina sérica não diferiu entre as idades experimentais, havendo porém, diferença entre tratamentos, sendo que os animais do tratamento 2 (colostro uma vez/dia) superaram (p < 0,05) os do tratamento 1 (leite) em relação a está variável. O ganho de peso no periodo foi maior (p < 0,05) no tratamento 3 (colostro duas vezes/dia) do que no tratamento 1 (leite). Concluiu-se que o fornecimento de colostro suplementar misturado ao leite duas vezes ao dia proporcionou melhor desempenho das bezerras, evidenciando o seu alto valor nutricional

    A generalized conformational energy function of DNA derived from molecular dynamics simulations

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    Proteins recognize DNA sequences by two different mechanisms. The first is direct readout, in which recognition is mediated by direct interactions between the protein and the DNA bases. The second is indirect readout, which is caused by the dependence of conformation and the deformability of the DNA structure on the sequence. Various energy functions have been proposed to evaluate the contribution of indirect readout to the free-energy changes in complex formations. We developed a new generalized energy function to estimate the dependence of the deformability of DNA on the sequence. This function was derived from molecular dynamics simulations previously conducted on B-DNA dodecamers, each of which had one possible tetramer sequence embedded at its center. By taking the logarithm of the probability distribution function (PDF) for the base-step parameters of the central base-pair step of the tetramer, its ability to distinguish the native sequence from random ones was superior to that with the previous method that approximated the energy function in harmonic form. From a comparison of the energy profiles calculated with these two methods, we found that the harmonic approximation caused significant errors in the conformational energies of the tetramers that adopted multiple stable conformations

    S-nitrosation and neuronal plasticity

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    Nitric oxide (NO) has long been recognized as a multifaceted participant in brain physiology. Despite the knowledge that was gathered over many years regarding the contribution of NO to neuronal plasticity, for example the ability of the brain to change in response to new stimuli, only in recent years have we begun to understand how NO acts on the molecular and cellular level to orchestrate such important phenomena as synaptic plasticity (modification of the strength of existing synapses) or the formation of new synapses (synaptogenesis) and new neurons (neurogenesis). Post-translational modification of proteins by NO derivatives or reactive nitrogen species is a non-classical mechanism for signalling by NO. S-nitrosation is a reversible post-translational modification of thiol groups (mainly on cysteines) that may result in a change of function of the modified protein. S-nitrosation of key target proteins has emerged as a main regulatory mechanism by which NO can influence several levels of brain plasticity, which are reviewed in this work. Understanding how S-nitrosation contributes to neural plasticity can help us to better understand the physiology of these processes, and to better address pathological changes in plasticity that are involved in the pathophysiology of several neurological diseases. Linked ArticlesThis article is part of a themed section on Pharmacology of the Gasotransmitters. To view the other articles in this section visitFEDER funds via Programa Operacional Factores de Competitividade (COMPETE); COST action [BM1005]; Foundation for Science and Technology (FCT, Portugal) [PTDC/SAU-OSD/0473/2012, PEst-C/SAU/LA0001/2013-2014, PEst-OE/EQB/LA0023/2013-2014]; Spanish-Portuguese Integrated Action grant [PRI-AIBPT-2011-1015/E-10/12]; FCT [SFRH/BD/77903/2011]; I3SNS programme (ISCIII, Spanish Government

    Automated parametric neutronics analysis of the Helium Cooled Pebble Bed breeder blanket with Be₁₂Ti

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    The Helium Cooled Pebble Bed (HCPB) breeder blanket is being developed as part of the European Fusion Programme. Part of the programme is to investigate blanket designs relevant for future demonstration fusion power plants. This paper presents neutronics analyses of the HCPB with an alternative neutron multiplier, Be12Ti which is incorporated into the design, replacing the current Be multiplier. A parameter study was performed for a range of geometries to identify the optimal heights of the lithium ceramic and neutron multiplier pebble beds. Automated creation of CAD models followed by conversion to constructive solid geometry (CSG) and unstructured mesh (UM) geometry allows the models to be useful for both neutronics simulations and engineering simulations. In this neutronics study simulations were performed using MCNP 6.1 to find the tritium breeding ratio, energy multiplication and the volumetric heat loads of different blanket designs. Combinations of geometry parameters and material choices that resulted in adequate TBR values were identified and will be further investigated with automated engineering simulations. This paper provides insight, supported by neutronics analysis, on the validity of the design and comments on some of the potential advantages and disadvantages of using Be12Ti in the Helium Cooled Pebble Bed (HCPB) breeder blanket. Blankets with Be12Ti neutron multiplier were found to produce less tritium but higher energy multiplication when compared to blankets with Be neutron multiplier

    Dual-specificity MAP kinase phosphatases in health and disease

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    Source at https://doi.org/10.1016/j.bbamcr.2018.09.002.It is well established that a family of dual-specificity MAP kinase phosphatases (MKPs) play key roles in the regulated dephosphorylation and inactivation of MAP kinase isoforms in mammalian cells and tissues. MKPs provide a mechanism of spatiotemporal feedback control of these key signalling pathways, but can also mediate crosstalk between distinct MAP kinase cascades and facilitate interactions between MAP kinase pathways and other key signalling modules. As our knowledge of the regulation, substrate specificity and catalytic mechanisms of MKPs has matured, more recent work using genetic models has revealed key physiological functions for MKPs and also uncovered potentially important roles in regulating the pathophysiological outcome of signalling with relevance to human diseases. These include cancer, diabetes, inflammatory and neurodegenerative disorders. It is hoped that this understanding will reveal novel therapeutic targets and biomarkers for disease, thus contributing to more effective diagnosis and treatment for these debilitating and often fatal conditions

    Maltooligosaccharides from JEG-3 Trophoblast-Like Cells Exhibit Immunoregulatory Properties

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    Citation Zhu A, Romero R, Huang J-B, Clark A, Petty HR. Maltooligosaccharides from JEG-3 trophoblast-like cells exhibit immunoregulatory properties. Am J Reprod Immunol 2011; 65: 54–64To better understand the immunoregulatory properties of trophoblasts, we have searched for small immunologically active carbohydrates derived from intact trophoblast-like cells.Using solid phase extraction coupled with HPLC and mass spectrometry methods, we have characterized a low molecular weight carbohydrate-rich fraction associated with JEG-3 cells. We have also tested the bioactivities of selected authentic oligosaccharides found in the oligosaccharide fraction.The most abundant components of the low molecular weight carbohydrate-rich fraction were maltotriose and maltotetraose, with detectable amounts of maltopentaose. When authentic maltooligosaccharides were tested using lymphocytes, IL-2 inhibition was observed. This activity was dependent upon the number of saccharide subunits, stereochemistry, and concentration. To further test maltooligosaccharide properties, maltopentose was attached to glass cover slips. Although spontaneous neutrophil motility was observed on unmodified and control surfaces, it was inhibited on maltooligosaccharide-derivatized surfaces.Maltooligosaccharides are associated with the trophoblast’s surface where they may exhibit immunoregulatory activities.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/79123/1/j.1600-0897.2010.00851.x.pd
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