Despite long traditional utilization and some reports on the antihyperglycemic and antihyperlipidemic action of Cassia siamea, the mechanisms involved have not been investigated yet. Thus, the ...objective of the present study was to investigate whether and how oral administration of the ethanolic extract of Cassia siamea Lam leaves (LECS) improves glucose and insulin homoeostasis, liver damage, and endothelial dysfunction in an experimental model of type 2 diabetes, the leptin-deficient ob/ob mice. Oxidative stress and protein expression of insulin-dependent and insulin -independent signaling pathways were studied. Obese (ob/ob) vs. control (ob/+) mice were treated daily with intragastric administration of either vehicle or LECS (200 mg/kg, per day) for 4 weeks. Fasting blood glucose, body weight, food intake, glucose and insulin tolerance, oxidative stress, and liver damage as well as vascular complications with respect to endothelial dysfunction were examined. Administration of LECS in obese mice significantly reduced blood glucose and insulin levels, improved glucose tolerance and insulin sensitivity, and restored the increase of circulating AST and ALT without modification of body weight and food intake. These effects were associated with increased activity of both insulin and AMPK pathways in the liver and skeletal muscles. Of particular interest, administration of LECS in obese mice completely prevented the endothelial dysfunction resulting from an increased NO⋅ and decreased reactive oxygen species (ROS) production in the aorta. Altogether, oral administration of LECS remarkably attenuates features of type 2 diabetes on glucose, hepatic inflammation, insulin resistance, endothelial function, and vascular oxidative stress, being as most of these effects are related to insulin-dependent and insulin-independent mechanisms. Therefore, this study points for the therapeutic potential of Cassia siamea in correcting both metabolic and vascular alterations linked to type 2 diabetes.
Correlations and clustering are of great importance in the study of the Nuclear Equation of State. Information on these items/aspects can be obtained using heavy-ion reactions which are described by ...dynamical theories. We propose a dataset that will be useful for improving the description of light cluster production in transport model approaches. The dataset combines published and new data and is presented in a form that allows direct comparison of the experiment with theoretical predictions. The dataset is ranging in bombarding energy from 32 to 1930 A MeV. In constructing this dataset, we put in evidence the existence of a change in the light cluster production mechanism that corresponds to a peak in deuteron production.
Scale issues are very meaningful in geography, but nowadays nobody knows how to explain their ubiquitous existence theoretically. Fractality is not an accident for all geographical objects. The aim ...of this article is to demonstrate to what extent the theory of scale relativity (SR) can be used to solve the problem of geographic scales. With it, we can explain why fractal objects are everywhere. First, we summarize geographic scale position, followed by introducing all tools to understand SR with basic definitions, scale in cartography, how to measure a scale, scales in and from nature, and scale and theoretical geography. Second, we quickly describe the theory of SR. Indeed, it is an elementary geometry around first principles, characterization of scale variables, and scale laws. This article also aims to clarify why geographical objects are non-fractal, in a first calculus, and fractal, in a second calculus with the theory of scale relativity. Third, we will underpin this position through several geographic cases with a karstological example, two urban areas (Montéliard and Avignon), and a hydrographic network and contours of level lines (Gardons). All of them will be carefully analyzed with a fractal analysis. Therefore, we conclude that in this case we are well and truly within the framework of the theory of SR, depending on the results.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
After a brief period of positive relations between Russia and NATO in the early 1990s, a whole series of crises in relations have led to a general deterioration of the relationship. These crises have ...resulted from two very different conceptions of self-identity and of the future of security in Europe. Although the divisions became evident already in before the turn of the millennium, the policies of Presidents Putin and Medvedev aimed at rebuilding Russia's role as a great power contributed further to the divisions. Three areas of NATO policy have been central to Russia's growing opposition to NATO-expansion eastward, the development of a missile shield, and the globalization of NATO's involvement. Prospects for a real reconciliation between Russia and NATO are not positive. Adapted from the source document.
The modification of the ground state properties of light atomic nuclei in the nuclear and stellar medium is addressed, using chemical equilibrium constants evaluated from a new analysis of the ...intermediate energy heavy-ion (Xe + Sn) collision data measured by the INDRA Collaboration. Three different reactions are considered, mainly differing by the isotopic content of the emission source. The thermodynamic conditions of the data samples are extracted from the measured multiplicities allowing for a parametrization of the in-medium modification, determined with the single hypothesis that the different nuclear species in a given sample correspond to a unique common value for the density of the expanding source. We show that this correction, which was not considered in previous analyses of chemical constants from heavy-ion collisions, is necessary, since the observables of the analyzed systems show strong deviations from the expected results for an ideal gas of free clusters. This dataset is further compared to a relativistic mean-field model, and seen to be reasonably compatible with a universal correction of the attractive σ-meson coupling.
Abstract
Purpose: Diffuse Intrinsic Pontine Glioma (DIPG), is a very aggressive pediatric cancer with poor overall survival and no effective treatment. Despite numerous clinical trials, the overall ...survival remains at 9 months after diagnosis and only radiotherapy has shown a relative efficacy. Therefore, it is primordial to increase our understanding of the biology of DIPG tumors, as well as finding new healthcare strategies to tackle this pediatric disease. Recently, we discovered that NQO1, a stress-related protein, was overexpressed in 3 out of 6 DIPG patient-derived cell lines, as well as in half of the primary tissues. Interestingly, NQO1 overexpression can be targeted by substrates that induce an excessive oxidative stress into the cells that finally push them to apoptosis, while normal surrounding tissues with basal expression of NQO1 would be keep safe.
Experimental procedure: This discovery prompted us to test in in vitro and in vivo assays a promising drug named isobutyl-deoxynyboquinone (IB-DNQ): a NQO1 bioactivatable substrate. We first tested the drug response of the 6 cell lines before testing it on orthotopic xenograft mouse models. We also investigated by which mechanism NQO1 is regulated in DIPG. Finally, we performed experiments in order to decipher by which mechanism NQO1 is regulated in DIPG.
Results: We saw that NQO1 overexpressing cells are very sensitive to the drug, compared to the cell lines with normal expression. Moreover, we started to validate the use of IB-DNQ in vivo using a DIPG cell line treated or not (mock) with IB-DNQ and also a NQO1-knockdown model in orthotopic xenograft mice models, confirming that IB-DNQ crosses the blood brain barrier and increases the overall survival. NQO1 increased expression in DIPG is surprisingly not due to a NRF2-mediated transcriptional regulation as we did not observe a correlation between NQO1 transcript abundance and protein expression in DIPG cell lines, indicating that NRF2 pathway could not be implicated, but translational or post-translational regulation could be operating. We performed a polysome profiling of 4 patient-derived cell lines, a protein stability assay and a large scale proteome for the 6 cell lines (pending results).
Conclusion: Our preliminary results, including drug efficacy, are very encouraging for the development of this new therapeutic in DIPG. This discovery represents a promising opportunity to tackle this devastating disease and a new hope for the patients and their families.
Citation Format: Maxime Henri Janin, Vanessa Ortiz Barahona, Pere Llinas Arias, Carolina De La Torre, Angel Montero Carcaboso, Andres Morales La Madrid, Paul Hergenrother, Manel Esteller. Positioning the NQO1-bioactivatable drug isobutyl-deoxynyboquinone in diffuse intrinsic pontine glioma (DIPG): an exceptional therapeutic opportunity in pediatric brain tumor abstract. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 5416.
This article presents an investigation of isospin equilibration in cross-bombarding $^{40,48}$Ca$+^{40,48}$Ca reactions at 35 MeV/nucleon, by comparing experimental data with filtered transport model ...calculations. Isospin diffusion is studied using the evolution of the isospin transport ratio with centrality. The asymmetry parameter $\delta=(N-Z)/A$ of the quasiprojectile (QP) residue is used as isospin-sensitive observable, while a recent method for impact parameter reconstruction is used for centrality sorting. A benchmark of global observables is proposed to assess the relevance of the antisymmetrized molecular dynamics (AMD) model, coupled to GEMINI++, in the study of dissipative collisions. Our results demonstrate the importance of considering cluster formation to reproduce observables used for isospin transport and centrality studies. Within the AMD model, we prove the applicability of the impact parameter reconstruction method, enabling a direct comparison to the experimental data for the investigation of isospin diffusion. For both, we evidence a tendency to isospin equilibration with an impact parameter decreasing from 9 to 3 fm, while the full equilibration is not reached. A weak sensitivity to the stiffness of the equation of state employed in the model is also observed, with a better reproduction of the experimental trend for the neutron-rich reactions.
L’équation d’état de la matière nucléaire est un outil primordial dans la description des collisions entreions lourds, mais également dans la description de la formation d’objets ou de phénomènes ...astrophysiques(structure des étoiles à neutrons, fusion d’étoiles à neutron). Établir l’équation d’état de la matière nucléairerequiert de définir de manière précise les conditions thermodynamiques (densité, température, asymétrie pro-ton/neutron) dans lesquelles le systèmes évolue. Dans ce travail, nous abordons la problématique de l’étatd’équilibration maximal qui est atteint dans les collisions entre ions lourds, en terme d’énergie et d’isospin.Pour cela, nous utilisons la base de données expérimentale du multi-détecteur INDRA construite par lacollaboration au cours de ces 25 dernières années, en nous intéressant plus particulièrement aux collisionscentrales dans le domaine de l’énergie de Fermi, entre 10 et 100 MeV/nucléon. Nous présentons ainsi dansce document, comment à l’aide de simulation dédiées, il nous a été possible de relier le pouvoir d’arrêt de lamatière nucléaire à la section efficace de collision nucléon-nucléon dans la matière nucléaire. Nous apportonségalement des éléments de réponse au regard du transport de l’isospin dans les collisions centrales à l’aidedes rapports isobariques A = 3 construits à partir des tritons et des hélium-3. Ces différents résultats nouspermettent de mettre en avant le nouveau dispositif expérimental mis en place par les collaborations INDRAet FAZIA : le multi-détecteur FAZIA. Ce dernier est le résultat d’une période de recherche et développementde dix ans, ayant abouti à un multi-détecteur embarquant son électronique numérique sous vide, avec desperformances d’identification accrues (mesure de la charge Z et de la masse A jusqu’à Z = 25) par rapportaux multi-détecteurs des générations précédentes.
The nuclear matter equation of the state is an essential tool in the description of heavy ion collisions,but also in the description of the formation of astrophysical objects or phenomena (neutron star structure,neutron stars fusion). Establishing the nuclear matter equation of state requires a proper definition of thethermodynamic conditions (density, temperature, proton/neutron asymmetry) in which the system evolves.In this work, we address the issue of equilibration reached in heavy ion collisions, in terms of energy andisospin. To do this, we use the experimental database of the INDRA array built by the collaboration over thepast 25 years, focusing on central collisions in the Fermi energy domain, between 10 and 100 MeV/nucleon.In this document, we present how, with the help of dedicated simulations, it has been possible to link thestopping power of nuclear matter to the in-medium nucleon-nucleon cross-section. We also provide someanswers regarding isospin transport in central collisions using the isobaric ratios A = 3 based on the tritonsand helium-3 particles. These different results allow us to highlight the new experimental apparatus devel-loped by the INDRA and FAZIA collaborations : the FAZIA array. The latter is the result of a ten-yearperiod of research and development, resulting in an array embedded its digital electronic under vacuum, withincreased identification performance (measurement of the Z charge and A mass up to Z = 25) compared tothe previous generations arrays.
The equation of state with light clusters for nuclear and stellar matter is determined using chemical equilibrium constants evaluated from the analysis of the recently published (Xe + Sn) heavy ion ...data, corresponding to three reactions with different isotopic contents of the emission source. The measured multiplicities are used to extract the thermodynamic properties, and an in-medium correction to the ideal gas internal partition function of the clusters is included in the analysis. This in-medium correction and its respective uncertainty are calculated via a Bayesian analysis, with the unique hypothesis that the different nuclear species in a given sample must correspond to a unique common value for the density of the expanding source. Different parameter sets for the correction are tested, and the effect of the radius of the clusters on the thermodynamics and on the chemical equilibrium constants is also addressed. It is shown that the equilibrium constants obtained are almost independent of the isospin content of the analysed systems. Finally, a comparison with a relativistic mean field model proves that data are consistent with a universal in-medium correction of the scalar σ-meson coupling for nucleons bound in clusters. The obtained value, gs/gs0=0.92±0.02, is larger than that obtained in a previous study not including in-medium effects in the data analysis. This result implies a smaller effect on the binding energy of the clusters and, as a consequence, larger melting densities, and an increased cluster contribution in supernova matter.
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