High glucose-induced hyperosmolarity contributes to COX-2 expression and angiogenesis: Implications for diabetic retinopathy

Background: We tested the hypothesis that glucose-induced hyperosmolarity, occurring in diabetic hyperglycemia, promotes retinal angiogenesis, and that interference with osmolarity signaling ameliorates excessive angiogenesis and retinopathy in vitro and in vivo. Methods and Results: We incubated human aortic (HAECs) and dermal microvascular endothelial cells (HMVECs) with glucose or mannitol for 24 h and tested them for protein levels and in vitro angiogenesis. We used the Ins2 Akita mice as a model of type 1 diabetes to test the in vivo relevance of in vitro observations. Compared to incubations with normal (5 mmol/L) glucose concentrations, cells exposed to both high glucose and high mannitol (at 30.5 or 50.5 mmol/L) increased expression of the water channel aquaporin-1 (AQP1) and cyclooxygenase (COX)-2. This was preceded by increased activity of the osmolarity-sensitive transcription factor Tonicity enhancer binding protein (TonEBP), and enhanced endothelial migration and tubulization in Matrigel, reverted by treatment with AQP1 and TonEBP siRNA. Retinas of Ins2 Akita mice showed increased levels of AQP1 and COX-2, as well as angiogenesis, all reverted by AQP1 siRNA intravitreal injections. Conclusions: Glucose-related hyperosmolarity seems to be able to promote angiogenesis and retinopathy through activation of TonEBP and possibly increasing expression of AQP1 and COX-2. Osmolarity signaling may be a target for therapy

third caesarean section in patient with myasthenia gravis

Abstract Myasthenia gravis (MG) is an autoimmune neuromuscular disease, characterised by muscle weakness and fatigability of the voluntary muscles, it affects young women in the second and third decade of life. We report a case of 30 years old multigravida woman with myasthenia gravis submitted to third iterative caesarean section with no adverse neonatal and maternal outcome. The course myathenia is highly variable and unpredictable during gestation and can change in subsequent pregnancies. Delivery specially, through caesarean section is very stressful and may cause severe myasthenic crisis. Although pregnancy and delivery represent particular events, that require more attention in these patients, they are not associated, in most cases, with higher risks of complications compared to normal pregnancy, delivery and postpartum period. According our experiences, in the management of myasthenic pregnant woman is necessary cooperation in a multidisciplinary team between obstetricians, neurologist, anaesthetist, and neonatologist for ensure an optimum outcome

Wilson Expansion of QCD Propagators at Three Loops: Operators of Dimension Two and Three

In this paper we construct the Wilson short distance operator product expansion for the gluon, quark and ghost propagators in QCD, including operators of dimension two and three, namely, A^2, m^2, m A^2, \ovl{\psi} \psi and m^3. We compute analytically the coefficient functions of these operators at three loops for all three propagators in the general covariant gauge. Our results, taken in the Landau gauge, should help to improve the accuracy of extracting the vacuum expectation values of these operators from lattice simulation of the QCD propagators.Comment: 20 pages, no figure

CD44 Expression Profile Varies According to Maturational Subtypes and Molecular Profiles of Pediatric T-Cell Lymphoblastic Leukemia.

CD44 is a glycoprotein expressed in leucocytes and a marker of leukemia-initiating cells, being shown to be important in the pathogenesis of T cell acute lymphoblastic leukemia (T-ALL). In this study, we have (i) identified the aberrant antigenic pattern of CD44 and its isoform CD44v6 in T-ALL; (ii) tested the association with different T-cell subtypes and genomic alterations; (iii) identified the impact of CD44 status in T-ALL outcome. Samples from 184 patients (123 T-ALL and 61 AML; <19 years) were analyzed throughout multiparametric flow cytometry. Mutations in N/KRAS, NOTCH1, FBXW7 as well as STIL-TAL1 and TLX3 rearrangements were detected using standard molecular techniques. CD44 expression was characterized in all T-ALL and AML cases. Compared with AML samples in which the median fluorescence intensity (MFI) was 79.1 (1-1272), T-ALL was relatively low, with MFI 43.2 (1.9-1239); CD44v6 expression was rarely found, MFI 1 (0.3-3.7). T-ALL immature subtypes (mCD3/CD1aneg) had a lower CD44 expression, MFI 57.5 (2.7-866.3), whereas mCD3/TCRγδpos cases had higher expressions, MFI 99.9 (16.4-866.3). NOTCH1 mut and STIL-TAL1 were associated with low CD44 expression, whereas N/KRAS mut and FBXW7 mut cases had intermediate expression. In relation to clinical features, CD44 expression was associated with tumor infiltrations (p = 0.065). However, no association was found with initial treatment responses and overall survival prediction. Our results indicate that CD44 is aberrantly expressed in T-ALL being influenced by different genomic alterations. Unraveling this intricate mechanism is required to place CD44 as a therapeutic target in T-ALL

Investigation of rock fragmentation during rockfalls and rock avalanches via 3-D discrete element analyses

This paper investigates the characteristics of dynamic rock fragmentation and its influence on the postfailure fragment trajectory. A series of numerical simulations by discrete element method (DEM) were performed for a simple rock block and slope geometry, where a particle agglomerate of prismatic shape is released along a sliding plane and subsequently collides onto a flat horizontal plane at a sharp kink point. The rock block is modeled as an assembly of bonded spherical particles with fragmentation arising from bond breakages. Bond strength and stiffness were calibrated against available experimental data. We analyzed how dynamic fragmentation occurs at impact, together with the generated fragment size distributions and consequently their runout for different slope topographies. It emerges that after impact, the vertical momentum of the granular system decreases sharply to nil, while the horizontal momentum increases suddenly and then decreases. The sudden boost of horizontal momentum can effectively facilitate the transport of fragments along the bottom floor. The rock fragmentation intensity is associated with the input energy and increases quickly with the slope angle. Gentle slopes normally lead to long spreading distance and large fragments, while steep slopes lead to high momentum boosts and impact forces, with efficient rock fragmentation and fine deposits. The fragment size decreases, while the fracture stress and fragment number both increase with the impact loading strain rate, supporting the experimental observations. The fragment size distributions can be well fitted by the Weibull's distribution function.Wile

Estereótipos e estigmas de obesos em propagandas com apelos de humor

Resumo Estereótipos positivos e negativos estão presentes em comunicações de marketing e são apresentados aos consumidores de forma indiscriminada. Com a atual epidemia de obesidade mundial, propagandas televisivas que se utilizam de indivíduos obesos em situações estigmatizadas não são exceção. Este artigo analisa o papel desempenhado por pessoas gordas em propagandas veiculadas na televisão sob a ótica de estigmas e estereótipos. Para tanto, realizaram-se três grupos focais com sujeitos que assistiram propagandas em que o protagonista era um indivíduo gordo. Fez-se inicialmente a análise do conteúdo de uma coleção de comerciais, bem como do corpus da pesquisa na qual se construiu uma figura representativa do “ser gordo” nessas mensagens. Sobressaiu nas análises que esses protagonistas apresentam-se com o objetivo de provocar o riso por meio do humor. Por conta disso, estigmas como “cômicos”, “estranhos” e “fracos” são formados a partir dos seus estereótipos e papéis desempenhados. Ao avançar nas investigações, questiona-se até que ponto essas interpretações podem comprometer a imagem da marca veiculada, considerando que o fenômeno obesidade está presente no quotidiano da maioria dos consumidores

Tunable kinetic proofreading in a model with molecular frustration

In complex systems, feedback loops can build intricate emergent phenomena, so that a description of the whole system cannot be easily derived from the properties of the individual parts. Here we propose that inter-molecular frustration mechanisms can provide non trivial feedback loops which can develop nontrivial specificity amplification. We show that this mechanism can be seen as a more general form of a kinetic proofreading mechanism, with an interesting new property, namely the ability to tune the specificity amplification by changing the reactants concentrations. This contrasts with the classical kinetic proofreading mechanism in which specificity is a function of only the reaction rate constants involved in a chemical pathway. These results are also interesting because they show that a wide class of frustration models exists that share the same underlining kinetic proofreading mechanisms, with even richer properties. These models can find applications in different areas such as evolutionary biology, immunology and biochemistry

Pixel and Voxel Representations of Graphs

We study contact representations for graphs, which we call pixel representations in 2D and voxel representations in 3D. Our representations are based on the unit square grid whose cells we call pixels in 2D and voxels in 3D. Two pixels are adjacent if they share an edge, two voxels if they share a face. We call a connected set of pixels or voxels a blob. Given a graph, we represent its vertices by disjoint blobs such that two blobs contain adjacent pixels or voxels if and only if the corresponding vertices are adjacent. We are interested in the size of a representation, which is the number of pixels or voxels it consists of. We first show that finding minimum-size representations is NP-complete. Then, we bound representation sizes needed for certain graph classes. In 2D, we show that, for $k$-outerplanar graphs with $n$ vertices, $\Theta(kn)$ pixels are always sufficient and sometimes necessary. In particular, outerplanar graphs can be represented with a linear number of pixels, whereas general planar graphs sometimes need a quadratic number. In 3D, $\Theta(n^2)$ voxels are always sufficient and sometimes necessary for any $n$-vertex graph. We improve this bound to $\Theta(n\cdot \tau)$ for graphs of treewidth $\tau$ and to $O((g+1)^2n\log^2n)$ for graphs of genus $g$. In particular, planar graphs admit representations with $O(n\log^2n)$ voxels