92 research outputs found

    hasil-peer-review-sunardi-0521057401-C.2.2

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    Mars' surface bears the imprint of valley networks formed billions of years ago. Whether these networks were formed by groundwater sapping, ice melt, or fluvial runoff has been debated for decades. These different scenarios have profoundly different implications for Mars' climatic history and thus for its habitability in the distant past. Recent studies on Earth revealed that valley networks in arid landscapes with more surface runoff branch at narrower angles, while in humid environments with more groundwater flow, branching angles are much wider. We find that valley networks on Mars generally tend to branch at narrow angles similar to those found in arid landscapes on Earth. This result supports the inference that Mars once had an active hydrologic cycle and that Mars' valley networks were formed primarily by overland flow erosion, with groundwater seepage playing only a minor role

    Non-Newtonian fluid flow through three-dimensional disordered porous media

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    We investigate the flow of various non-Newtonian fluids through three-dimensional disordered porous media by direct numerical simulation of momentum transport and continuity equations. Remarkably, our results for power-law (PL) fluids indicate that the flow, when quantified in terms of a properly modified permeability-like index and Reynolds number, can be successfully described by a single (universal) curve over a broad range of Reynolds conditions and power-law exponents. We also study the flow behavior of Bingham fluids described in terms of the Herschel-Bulkley model. In this case, our simulations reveal that the interplay of ({\it i}) the disordered geometry of the pore space, ({\it ii}) the fluid rheological properties, and ({\it iii}) the inertial effects on the flow is responsible for a substantial enhancement of the macroscopic hydraulic conductance of the system at intermediate Reynolds conditions. This anomalous condition of ``enhanced transport'' represents a novel feature for flow in porous materials.Comment: 5 pages, 5 figures. This article appears also in Physical Review Letters 103 194502 (2009

    Determination of the Effective Viscosity of Non-newtonian Fluids Flowing Through Porous Media

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    When non-Newtonian fluids flow through porous media, the topology of the pore space leads to a broad range of flow velocities and shear rates. Consequently, the local viscosity of the fluid also varies in space with a non-linear dependence on the Darcy velocity. Therefore, an effective viscosity μeff is usually used to describe the flow at the Darcy scale. For most non-Newtonian flows the rheology of the fluid can be described by a (non linear) function of the shear rate. Current approaches estimate the effective viscosity by first calculating an effective shear rate mainly by adopting a power-law model for the rheology and including an empirical correction factor. In a second step this averaged shear rate is used together with the real rheology of the fluid to calculate μeff. In this work, we derive a semi-analytical expression for the local viscosity profile using a Carreau type fluid, which is a more broadly applicable model than the power-law model. By solving the flow equations in a circular cross section of a capillary we are able to calculate the average viscous resistance 〈μ〉 directly as a spatial average of the local viscosity. This approach circumvents the use of classical capillary bundle models and allows to upscale the viscosity distribution in a pore with a mean pore size to the Darcy scale. Different from commonly used capillary bundle models, the presented approach does neither require tortuosity nor permeability as input parameters. Consequently, our model only uses the characteristic length scale of the porous media and does not require empirical coefficients. The comparison of the proposed model with flow cell experiments conducted in a packed bed of monodisperse spherical beads shows, that our approach performs well by only using the physical rheology of the fluid, the porosity and the estimated mean pore size, without the need to determine an effective shear rate. The good agreement of our model with flow experiments and existing models suggests that the mean viscosity 〈μ〉 is a good estimate for the effective Darcy viscosity μeff providing physical insight into upscaling of non-Newtonian flows in porous media

    Erufosine, a novel alkylphosphocholine, in acute myeloid leukemia: single activity and combination with other antileukemic drugs

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    Alkylphosphocholines represent a new class of cytostatic drugs with a novel mode of action. Erufosine (ErPC3), the first compound of this class that can be administered intravenously, has recently been shown to be active against human tumor and leukemic cell lines. METHODS: In order to evaluate the antileukemic potential of ErPC3 in acute myeloid leukemia (AML) the lethal concentration 50% (LC 50) was determined using WST-1 assay. For analysis of cell death, staining for Annexin V and activated caspase 3 was performed. An interaction analysis was performed by calculation of combination index and construction of isobolograms. RESULTS: The LC 50 was 7.4 microg/ml after 24 h and 3.2 microg/ml after 72 h in HL 60 cells and 30.1 and 8.6 microg/ml, respectively, in 19 fresh samples from patients with AML. ErPC3 was found to be cytotoxic in HL60 cells with distinct activation of caspase 3. ErPC3 was not cross-resistant with cytarabine, idarubicine and etoposide as shown by the linear relation of respective LC 50s. The latter agents, however, exerted an additive cytotoxicity in combination with ErPC3 as revealed by isobologram analysis and combination index, although results are uneven for idarubicine. CONCLUSION: Based on these data ErPC3 appears as a novel antileukemic candidate drug, which needs to be explored further in the treatment of AML

    Expression-Dependent Folding of Interphase Chromatin

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    Multiple studies suggest that chromatin looping might play a crucial role in organizing eukaryotic genomes. To investigate the interplay between the conformation of interphase chromatin and its transcriptional activity, we include information from gene expression profiles into a polymer model for chromatin that incorporates genomic loops. By relating loop formation to transcriptional activity, we are able to generate chromosome conformations whose structural and topological properties are consistent with experimental data. The model particularly allows to reproduce the conformational variations that are known to occur between highly and lowly expressed chromatin regions. As previously observed in experiments, lowly expressed regions of the simulated polymers are much more compact. Due to the changes in loop formation, the distributions of chromatin loops are also expression-dependent and exhibit a steeper decay in highly active regions. As a results of entropic interaction between differently looped parts of the chromosome, we observe topological alterations leading to a preferential positioning of highly transcribed loci closer to the surface of the chromosome territory. Considering the diffusional behavior of the chromatin fibre, the simulations furthermore show that the higher the expression level of specific parts of the chromatin fibre is, the more dynamic they are. The results exhibit that variations of loop formation along the chromatin fibre, and the entropic changes that come along with it, do not only influence the structural parameters on the local scale, but also effect the global chromosome conformation and topology

    MicroRNA-96 Directly Inhibits γ-Globin Expression in Human Erythropoiesis

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    Fetal hemoglobin, HbF (α2γ2), is the main hemoglobin synthesized up to birth, but it subsequently declines and adult hemoglobin, HbA (α2β2), becomes predominant. Several studies have indicated that expression of the HbF subunit γ-globin might be regulated post-transcriptionally. This could be confered by ∼22-nucleotide long microRNAs that associate with argonaute proteins to specifically target γ-globin mRNAs and inhibit protein expression. Indeed, applying immunopurifications, we found that γ-globin mRNA was associated with argonaute 2 isolated from reticulocytes that contain low levels of HbF (<1%), whereas association was significantly lower in reticulocytes with high levels of HbF (90%). Comparing microRNA expression in reticulocytes from cord blood and adult blood, we identified several miRNAs that were preferentially expressed in adults, among them miRNA-96. The overexpression of microRNA-96 in human ex vivo erythropoiesis decreased γ-globin expression by 50%, whereas the knock-down of endogenous microRNA-96 increased γ-globin expression by 20%. Moreover, luciferase reporter assays showed that microRNA-96 negatively regulates expression of γ-globin in HEK293 cells, which depends on a seedless but highly complementary target site located within the coding sequence of γ-globin. Based on these results we conclude that microRNA-96 directly suppresses γ-globin expression and thus contributes to HbF regulation

    Associations of common breast cancer susceptibility alleles with risk of breast cancer subtypes in BRCA1 and BRCA2 mutation carriers

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    Introduction: More than 70 common alleles are known to be involved in breast cancer (BC) susceptibility, and several exhibit significant heterogeneity in their associations with different BC subtypes. Although there are differences in the association patterns between BRCA1 and BRCA2 mutation carriers and the general population for several loci, no study has comprehensively evaluated the associations of all known BC susceptibility alleles with risk of BC subtypes in BRCA1 and BRCA2 carriers. Methods: We used data from 15,252 BRCA1 and 8,211 BRCA2 carriers to analyze the associations between approximately 200,000 genetic variants on the iCOGS array and risk of BC subtypes defined by estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor 2 (HER2) and triple-negative- (TN) status; morphologic subtypes; histological grade; and nodal involvement. Results: The estimated BC hazard ratios (HRs) for the 74 known BC alleles in BRCA1 carriers exhibited moderate correlations with the corresponding odds ratios from the general population. However, their associations with ER-positive BC in BRCA1 carriers were more consistent with the ER-positive as
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