Predicting the Transport Properties of Aerosol Particles in Creeping Flow from the Continuum to the Free Molecule Regime

The transport of nanoscale aerosol particles plays an important role in many natural and industrial processes. Despite its importance, the transport behavior of aerosol aggregates is poorly understood, largely due its complex dependence on particle size, shape, and orientation. Often, these particles are in the transition regime, where neither the continuum approximation for large particles nor the free molecule approximation for small particles is valid. At present, methods for calculating the aerodynamic force on and diffusive behavior of fractal aggregates in the transition regime either rely upon scaling laws fitted to experimental data or computationally-intensive direct simulation Monte Carlo or molecular dynamics approaches. Thus, there is a pressing need for a new method for determining aerosol transport properties. This dissertation introduces such a method for calculating the drag and torque on an aerosol aggregate as a function of the primary sphere size and the aggregate size and shape. This method is an extension of Kirkwood-Riseman theory to the transition regime, using an appropriate model for interactions between the individual spheres in an aggregate. This dissertation also describes the application of this extended Kirkwood-Riseman (EKR) method to a number of problems related to aerosol transport, including computation of the scalar translational and rotational friction coefficients of aggregates formed by diffusion-limited processes, analysis of the effects of alignment on particle migration in an electric field, and the strength of interactions between particles due to their effects on the surrounding fluid flow field. In each of these applications, results from the EKR method are in good agreement with published experimental data and computational results. EKR results also demonstrate that particle translational and rotational behavior becomes more continuum-like as both primary particle size and the number of spheres in the aggregate increase. Using these results, new correlations have been developed for the translational and rotational friction coefficients of aggregates formed by diffusion-limited processes (e.g.~soot); these correlations are more accurate than the empirical models currently available in the literature

Strategies for printing fibers and post-processing for ceramic matrix composites (CMCs)

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Development of MELCOR Input Techniques for High Temperature Gas-Cooled Reactor Analysis

High Temperature Gas-cooled Reactors (HTGRs) can provide clean electricity,as well as process heat that can be used to produce hydrogen for transportation and other sectors. A prototypic HTGR, the Next Generation Nuclear Plant (NGNP),will be built at Idaho National Laboratory.The need for HTGR analysis tools and methods has led to the addition of gas-cooled reactor (GCR) capabilities to the light water reactor code MELCOR. MELCOR will be used by the Nuclear Regulatory Commission licensing of the NGNP and other HTGRs. In the present study, new input techniques have been developed for MELCOR HTGR analysis. These new techniques include methods for modeling radiation heat transfer between solid surfaces in an HTGR, calculating fuel and cladding geometric parameters for pebble bed and prismatic block-type HTGRs, and selecting appropriate input parameters for the reflector component in MELCOR. The above methods have been applied to input decks for a water-cooled reactor cavity cooling system (RCCS); the 400 MW Pebble Bed Modular Reactor (PBMR), the input for which is based on a code-to-code benchmark activity; and the High Temperature Test Facility (HTTF), which is currently in the design phase at Oregon State University. RCCS results show that MELCOR accurately predicts radiation heat transfer rates from the vessel but may overpredict convective heat transfer rates and RCCS coolant flow rates. PBMR results show that thermal striping from hot jets in the lower plenum during steady-state operations, and in the upper plenum during a pressurized loss of forced cooling accident, may be a major design concern. Hot jets could potentially melt control rod drive mechanisms or cause thermal stresses in plenum structures. For the HTTF, results will provide data to validate MELCOR for HTGR analyses. Validation will be accomplished by comparing results from the MELCOR representation of the HTTF to experimental results from the facility. The validation process can be automated using a modular code written in Python, which is described here

Activity Patterns Govern Synapse-Specific AMPA Receptor Trafficking between Deliverable and Synaptic Pools

SummaryIn single neurons, glutamatergic synapses receiving distinct afferent inputs may contain AMPA receptors (-Rs) with unique subunit compositions. However, the cellular mechanisms by which differential receptor transport achieves this synaptic diversity remain poorly understood. In lateral geniculate neurons, we show that retinogeniculate and corticogeniculate synapses have distinct AMPA-R subunit compositions. Under basal conditions at both synapses, GluR1-containing AMPA-Rs are transported from an anatomically defined reserve pool to a deliverable pool near the postsynaptic density (PSD), but further incorporate into the PSD or functional synaptic pool only at retinogeniculate synapses. Vision-dependent activity, stimulation mimicking retinal input, or activation of CaMKII or Ras signaling regulated forward GluR1 trafficking from the deliverable pool to the synaptic pool at both synapses, whereas Rap2 signals reverse GluR1 transport at retinogeniculate synapses. These findings suggest that synapse-specific AMPA-R delivery involves constitutive and activity-regulated transport steps between morphological pools, a mechanism that may extend to the site-specific delivery of other membrane protein complexes

Ref-1/APE1 Inhibition with Novel Small Molecules Blocks Ocular Neovascularization

Ocular neovascular diseases like wet age-related macular degeneration are a major cause of blindness. Novel therapies are greatly needed for these diseases. One appealing antiangiogenic target is reduction-oxidation factor 1–apurinic/apyrimidinic endonuclease 1 (Ref-1/APE1). This protein can act as a redox-sensitive transcriptional activator for nuclear factor (NF)-κB and other proangiogenic transcription factors. An existing inhibitor of Ref-1’s function, APX3330, previously showed antiangiogenic effects. Here, we developed improved APX3330 derivatives and assessed their antiangiogenic activity. We synthesized APX2009 and APX2014 and demonstrated enhanced inhibition of Ref-1 function in a DNA-binding assay compared with APX3330. Both compounds were antiproliferative against human retinal microvascular endothelial cells (HRECs; GI50 APX2009: 1.1 μM, APX2014: 110 nM) and macaque choroidal endothelial cells (Rf/6a; GI50 APX2009: 26 μM, APX2014: 5.0 μM). Both compounds significantly reduced the ability of HRECs and Rf/6a cells to form tubes at mid-nanomolar concentrations compared with control, and both significantly inhibited HREC and Rf/6a cell migration in a scratch wound assay, reducing NF-κB activation and downstream targets. Ex vivo, APX2009 and APX2014 inhibited choroidal sprouting at low micromolar and high nanomolar concentrations, respectively. In the laser-induced choroidal neovascularization mouse model, intraperitoneal APX2009 treatment significantly decreased lesion volume by 4-fold compared with vehicle (P < 0.0001, ANOVA with Dunnett’s post-hoc tests), without obvious intraocular or systemic toxicity. Thus, Ref-1 inhibition with APX2009 and APX2014 blocks ocular angiogenesis in vitro and ex vivo, and APX2009 is an effective systemic therapy for choroidal neovascularization in vivo, establishing Ref-1 inhibition as a promising therapeutic approach for ocular neovascularization

Análisis sincrónico de la gobernanza universitaria: una mirada teórica a los años sesenta y setenta

Resumen Estudiar las perspectivas en el campo del gobierno de las universidades tiene cada día mayor preeminencia, especialmente si se toma en cuenta la incuestionable necesidad de avanzar hacía organizaciones más eficientes, conectadas con las expectativas que sobre ellas tiene la sociedad. Considerando este escenario, el trabajo se ha planteado como propósito central realizar un análisis de carácter sincrónico del concepto de gobernanza y la constitución de los gobiernos universitarios. Desde el punto de vista metodológico se utilizaron fuentes secundarias: una revisión de papers publicados esencialmente en revistas de habla inglesa. El estudio comprende las décadas del sesenta y el setenta. Se centra en las raíces del concepto de gobernanza universitaria, en la delineación de los actores que participan en sus gobiernos y en las relaciones de poder que fluyen entre ellos.Entre las principales conclusiones, se pueden destacar como el estamento académico desde el principio de las universidades ha ocupado el rol casi plenipotenciario en su respectivo gobierno, producto de esto, en el correr del desarrollo y mientras la complejidad organizacional se incrementaba, es que fue necesario incorporar nuevos actores a los sistemas de gestión; todo lo anterior, teniendo en cuenta que dos elementos han sido fundamentales para la sobrevivencia de este tipo de instituciones, la legitimidad otorgada por la sociedad y los principios de estrategias del ámbito de la gestión

The INT6 Cancer Gene and MEK Signaling Pathways Converge during Zebrafish Development

BACKGROUND: Int-6 (integration site 6) was identified as an oncogene in a screen of tumorigenic mouse mammary tumor virus (MMTV) insertions. INT6 expression is altered in human cancers, but the precise role of disrupted INT6 in tumorigenesis remains unclear, and an animal model to study Int-6 physiological function has been lacking. PRINCIPAL FINDINGS: Here, we create an in vivo model of Int6 function in zebrafish, and through genetic and chemical-genetic approaches implicate Int6 as a tissue-specific modulator of MEK-ERK signaling. We find that Int6 is required for normal expression of MEK1 protein in human cells, and for Erk signaling in zebrafish embryos. Loss of either Int6 or Mek signaling causes defects in craniofacial development, and Int6 and Erk-signaling have overlapping domains of tissue expression. SIGNIFICANCE: Our results provide new insight into the physiological role of vertebrate Int6, and have implications for the treatment of human tumors displaying altered INT6 expression

Manipulating the alpha level cannot cure significance testing

We argue that making accept/reject decisions on scientific hypotheses, including a recent call for changing the canonical alpha level from p = 0.05 to p = 0.005, is deleterious for the finding of new discoveries and the progress of science. Given that blanket and variable alpha levels both are problematic, it is sensible to dispense with significance testing altogether. There are alternatives that address study design and sample size much more directly than significance testing does; but none of the statistical tools should be taken as the new magic method giving clear-cut mechanical answers. Inference should not be based on single studies at all, but on cumulative evidence from multiple independent studies. When evaluating the strength of the evidence, we should consider, for example, auxiliary assumptions, the strength of the experimental design, and implications for applications. To boil all this down to a binary decision based on a p-value threshold of 0.05, 0.01, 0.005, or anything else, is not acceptable