Fluid Flows of Mixed Regimes in Porous Media

In porous media, there are three known regimes of fluid flows, namely, pre-Darcy, Darcy and post-Darcy. Because of their different natures, these are usually treated separately in literature. To study complex flows when all three regimes may be present in different portions of a same domain, we use a single equation of motion to unify them. Several scenarios and models are then considered for slightly compressible fluids. A nonlinear parabolic equation for the pressure is derived, which is degenerate when the pressure gradient is either small or large. We estimate the pressure and its gradient for all time in terms of initial and boundary data. We also obtain their particular bounds for large time which depend on the asymptotic behavior of the boundary data but not on the initial one. Moreover, the continuous dependence of the solutions on initial and boundary data, and the structural stability for the equation are established.Comment: 33 page

Hypoxic Preconditioning Enhances Survival and Proangiogenic Capacity of Human First Trimester Chorionic Villus-Derived Mesenchymal Stem Cells for Fetal Tissue Engineering.

Prenatal stem cell-based regenerative therapies have progressed substantially and have been demonstrated as effective treatment options for fetal diseases that were previously deemed untreatable. Due to immunoregulatory properties, self-renewal capacity, and multilineage potential, autologous human placental chorionic villus-derived mesenchymal stromal cells (CV-MSCs) are an attractive cell source for fetal regenerative therapies. However, as a general issue for MSC transplantation, the poor survival and engraftment is a major challenge of the application of MSCs. Particularly for the fetal transplantation of CV-MSCs in the naturally hypoxic fetal environment, improving the survival and engraftment of CV-MSCs is critically important. Hypoxic preconditioning (HP) is an effective priming approach to protect stem cells from ischemic damage. In this study, we developed an optimal HP protocol to enhance the survival and proangiogenic capacity of CV-MSCs for improving clinical outcomes in fetal applications. Total cell number, DNA quantification, nuclear area test, and cell viability test showed HP significantly protected CV-MSCs from ischemic damage. Flow cytometry analysis confirmed HP did not alter the immunophenotype of CV-MSCs. Caspase-3, MTS, and Western blot analysis showed HP significantly reduced the apoptosis of CV-MSCs under ischemic stimulus via the activation of the AKT signaling pathway that was related to cell survival. ELISA results showed HP significantly enhanced the secretion of vascular endothelial growth factor (VEGF) and hepatocyte growth factor (HGF) by CV-MSCs under an ischemic stimulus. We also found that the environmental nutrition level was critical for the release of brain-derived neurotrophic factor (BDNF). The angiogenesis assay results showed HP-primed CV-MSCs could significantly enhance endothelial cell (EC) proliferation, migration, and tube formation. Consequently, HP is a promising strategy to increase the tolerance of CV-MSCs to ischemia and improve their therapeutic efficacy in fetal clinical applications

New calculations and measurements of the Coulomb cross-section for the production of direct electron pairs by high energy nuclei

Recently, new calculations were made of the direct Coulomb pair cross section that rely less in arbitrary parameters. More accurate calculations of the cross section down to low pair energies were made. New measurements of the total direct electron pair yield, and the energy and angular distribution of the electron pairs in emulsion were made for O-16 at 60 and 200 GeV/amu at S-32 at 200 GeV/amu which give satisfactory agreement with the new calculations. These calculations and measurements are presented along with previous accelerator measurements made of this effect during the last 40 years. The microscope scanning criteria used to identify the direct electron pairs is described. Prospects for application of the pair method to cosmic ray energy measurements in the region 10 (exp 13) to 10 (exp 15) eV/amu are discussed

Identification of a Unique TGF-β Dependent Molecular and Functional Signature in Microglia

Microglia are myeloid cells of the central nervous system (CNS) that participate both in normal CNS function and disease. We investigated the molecular signature of microglia and identified 239 genes and 8 microRNAs that were uniquely or highly expressed in microglia vs. myeloid and other immune cells. Out of 239 genes, 106 were enriched in microglia as compared to astrocytes, oligodendrocytes and neurons. This microglia signature was not observed in microglial lines or in monocytes recruited to the CNS and was also observed in human microglia. Based on this signature, we found a crucial role for TGF-β in microglial biology that included: 1) the requirement of TGF-β for the in vitro development of microglia that express the microglial molecular signature characteristic of adult microglia; and 2) the absence of microglia in CNS TGF-β1 deficient mice. Our results identify a unique microglial signature that is dependent on TGF-β signaling which provides insights into microglial biology and the possibility of targeting microglia for the treatment of CNS disease

Cash Transfers, Early Marriage, and Fertility in Malawi and Zambia

There is increasing interest in the ability of cash transfers to facilitate safe transitions to adulthood in low-income settings; however, evidence from scaled-up government programming demonstrating this potential is scarce. Using two experimental evaluations of unconditional cash transfers targeted to ultra-poor and labor-constrained households over approximately three years in Malawi and Zambia, we examine whether cash transfers delayed early marriage and pregnancy among youth aged 14 to 21 years at baseline. Although we find strong impacts on poverty and schooling, two main pathways hypothesized in the literature, we find limited impacts on safe transition outcomes for both males and females. In addition, despite hypotheses that social norms may constrain potential impacts of cash transfer programs, we show suggestive evidence that pre-program variation in social norms across communities does not significantly affect program impact. We conclude with policy implications and suggestions for future research

The Local Food Environment and Body Mass Index among the Urban Poor in Accra, Ghana

Obesity in the sub-Saharan Africa region has been portrayed as a problem of affluence, partly because obesity has been found to be more common in urban areas and among the rich. Recent findings, however, reveal rising prevalence among the poor particularly the urban poor. A growing body of literature mostly in Western countries shows that obesity among the poor is partly the result of an obesogenic-built environment. Such studies are lacking in the African context. This study examines the characteristics of the local food environment in an urban poor setting in Accra, Ghana and further investigates the associated risk of obesity for residents. Data on the local food environment was collected using geographic positioning system (GPS) technology. The body mass indices (BMI) of females (15-49 years) and males (15-59 years) were calculated from measured weight and height. Data on the socio-demographic characteristics and lifestyle behaviors of respondents was also collected through a household survey. Spatial analysis tools were used to examine the characteristics of the local food environment while the influence of the food environment on BMI was examined using a two-level multilevel model. The measures of the food environment constituted the level 2 factors while individual socio-demographic characteristics and lifestyle behaviors constituted the level 1 factors. The local food environment in the study communities is suggestive of an obesogenic food environment characterized by an abundance of out-of-home cooked foods, convenience stores, and limited fruits and vegetables options. The results of the multilevel analysis reveal a 0.2 kg/m(2) increase in BMI for every additional convenience store and a 0.1 kg/m(2) reduction in BMI for every out-of-home cooked food place available in the study area after controlling for individual socio-demographic characteristics, lifestyle behaviors, and community characteristics. The findings of this study indicate that the local food environment in urban poor Accra is associated with increased risk of obesity through providing access to convenience stores. In order to reduce the risk of obesity in these urban poor communities, there is the need to regulate the availability of and access to convenience stores while also encouraging healthier offerings in convenience stores

Mitochondrial Targeted Coenzyme Q, Superoxide, and Fuel Selectivity in Endothelial Cells

Background Previously, we reported that the “antioxidant” compound “mitoQ” (mitochondrial-targeted ubiquinol/ubiquinone) actually increased superoxide production by bovine aortic endothelial (BAE) cell mitochondria incubated with complex I but not complex II substrates. Methods and Results To further define the site of action of the targeted coenzyme Q compound, we extended these studies to include different substrate and inhibitor conditions. In addition, we assessed the effects of mitoquinone on mitochondrial respiration, measured respiration and mitochondrial membrane potential in intact cells, and tested the intriguing hypothesis that mitoquinone might impart fuel selectivity in intact BAE cells. In mitochondria respiring on differing concentrations of complex I substrates, mitoquinone and rotenone had interactive effects on ROS consistent with redox cycling at multiple sites within complex I. Mitoquinone increased respiration in isolated mitochondria respiring on complex I but not complex II substrates. Mitoquinone also increased oxygen consumption by intact BAE cells. Moreover, when added to intact cells at 50 to 1000 nM, mitoquinone increased glucose oxidation and reduced fat oxidation, at doses that did not alter membrane potential or induce cell toxicity. Although high dose mitoquinone reduced mitochondrial membrane potential, the positively charged mitochondrial-targeted cation, decyltriphenylphosphonium (mitoquinone without the coenzyme Q moiety), decreased membrane potential more than mitoquinone, but did not alter fuel selectivity. Therefore, non-specific effects of the positive charge were not responsible and the quinone moiety is required for altered nutrient selectivity. Conclusions In summary, the interactive effects of mitoquinone and rotenone are consistent with redox cycling at more than one site within complex I. In addition, mitoquinone has substrate dependent effects on mitochondrial respiration, increases repiration by intact cells, and alters fuel selectivity favoring glucose over fatty acid oxidation at the intact cell level.This work was supported by Veterans Affairs Medical Research Funds and grant DK25295 from the National Institutes of Health