Effect Of Confined Impinging Jet Mixing Processing Parameters On Poly (Lactic Acid) Nanoparticle Morphology

Biodegradable nanoparticles are at the forefront of drug delivery research as they provide numerous advantages over traditional drug delivery methods. An important factor affecting the ability of nanoparticles to circulate within the blood stream and interact with cells is their morphology. In this study a novel processing method, confined impinging jet mixing, was used to form poly (lactic acid) nanoparticles through a solvent-diffusion process with Pluronic F-127 being used as a stabilizing agent. This study focused on the effects of Reynolds number (flow rate), surfactant presence in mixing, and polymer concentration on the morphology of poly (lactic acid) nanoparticles. In addition to looking at the parameters affecting poly (lactic acid) morphology, this study attempted to improve nanoparticle isolation and purification methods to increase nanoparticle yield and ensure specific morphologies were not being excluded during isolation and purification. The isolation and purification methods used in this study were centrifugation and a stir cell. This study successfully produced particles having pyramidal and cubic morphologies. Despite successful production of these morphologies the yield of non-spherical particles was very low, additionally great variability existed between redundant trails. Surfactant was determined to be very important for the stabilization of nanoparticles in solution but appears to be unnecessary for the formation of nanoparticles. Isolation and purification methods that produce a high yield of surfactant free particles have still not been perfected and additional testing will be necessary for improvement.¿

Detrital Zircon Evidence for Mixing of Mazatzal Province Age Detritus With Yavapai Age (ca. 1700-1740 Ma) and Older Detritus in the ca. 1650 Ma Mazatzal Province of Central New Mexico, USA

Preliminary detrital zircon age distributions from Mazatzal crustal province quartzite and schist exposed in the Manzano Mountains and Pedernal Hills of central New Mexico are consistent with a mixture of detritus from Mazatzal age (ca. 1650 Ma), Yavapai age (ca. 1720 Ma.), and older sources. A quartzite sample from the Blue Springs Formation in the Manzano Mountains yielding 67 concordant grain analyses shows two dominant age peaks of 1737 Ma and 1791 Ma with a minimum peak age of 1652 Ma. Quartzite and micaceous quartzite samples from near Pedernal Peak give unimodal peak ages of ca. 1695 Ma and 1738 Ma with minimum detrital zircon ages of ca. 1625 Ma and 1680 Ma, respectively. A schist sample from the southern exposures of the Pedernal Hills area gives a unimodal peak age of 1680 Ma with a minimum age of ca. 1635 Ma. Minor amounts of older detritus (>1800 Ma) possibly reflect Trans-Hudson, Wyoming, Mojave Province, and older Archean sources and aid in locating potential source terrains for these detrital zircon. The Blue Springs Formation metarhyolite from near the top of the Proterozoic section in the Manzano Mountains yields 71 concordant grains that show a preliminary U-Pb zircon crystallization age of 1621 ¿ 5 Ma, which provides a minimum age constraint for deposition in the Manzano Mountains. Normalized probability plots from this study are similar to previously reported age distributions in the Burro and San Andres Mountains in southern New Mexico and suggest that Yavapai Province age detritus was deposited and intermingled with Mazatzal Province age detritus across much of the Mazatzal crustal province in New Mexico. This data shows that the tectonic evolution of southwestern Laurentia is associated with multiple orogenic events. Regional metamorphism and deformation in the area must postdate the Mazatzal Orogeny and ca. 1610 Ma ¿ 1620 Ma rhyolite crystallization and is attributed to the Mesoproterozoic ca. 1400 ¿ 1480 Ma Picuris Orogeny.

Continuous measurements of methane mixing ratios from ice cores

This work presents a new, field-deployable technique for continuous, high-resolution measurements of methane mixing ratios from ice cores. The technique is based on a continuous flow analysis system, where ice core samples cut along the long axis of an ice core are melted continuously. The past atmospheric air contained in the ice is separated from the melt water stream via a system for continuous gas extraction. The extracted gas is dehumidified and then analyzed by a Wavelength Scanned-Cavity Ring Down Spectrometer for methane mixing ratios. We assess the performance of the new measurement technique in terms of precision (±0.8 ppbv, 1σ), accuracy (±8 ppbv), temporal (ca. 100 s), and spatial resolution (ca. 5 cm). Using a firn air transport model, we compare the resolution of the measurement technique to the resolution of the atmospheric methane signal as preserved in ice cores in Greenland. We conclude that our measurement technique can resolve all climatically relevant variations as preserved in the ice down to an ice depth of at least 1980 m (66 000 yr before present) in the North Greenland Eemian Ice Drilling ice core. Furthermore, we describe the modifications, which are necessary to make a commercially available spectrometer suitable for continuous methane mixing ratio measurements from ice cores.

A Diagnostic Test for the Mixing Distribution in a Generalised Linear Mixed Model

We introduce a diagnostic test for the mixing distribution in a generalised linear mixed model. The test is based on the difference between the marginal maximum likelihood and conditional maximum likelihood estimates of a subset of the fixed effects in the model. We derive the asymptotic variance of this difference, and propose a test statistic that has a limiting chi-square distribution under the null hypothesis that the mixing distribution is correctly specified. For the important special case of the logistic regression model with random intercepts, we evaluate via simulation the power of the test in finite samples under several alternative distributional forms for the mixing distribution. We illustrate the method by applying it to data from a clinical trial investigating the effects of hormonal contraceptives in women.

Multilevel Latent Class Models with Dirichlet Mixing Distribution

Latent class analysis (LCA) and latent class regression (LCR) are widely used for modeling multivariate categorical outcomes in social sciences and biomedical studies. Standard analyses assume data of different respondents to be mutually independent, excluding application of the methods to familial and other designs in which participants are clustered. In this paper, we develop multilevel latent class model, in which subpopulation mixing probabilities are treated as random effects that vary among clusters according to a common Dirichlet distribution. We apply the Expectation-Maximization (EM) algorithm for model fitting by maximum likelihood (ML). This approach works well, but is computationally intensive when either the number of classes or the cluster size is large. We propose a maximum pairwise likelihood (MPL) approach via a modified EM algorithm for this case. We also show that a simple latent class analysis, combined with robust standard errors, provides another consistent, robust, but less efficient inferential procedure. Simulation studies suggest that the three methods work well in finite samples, and that the MPL estimates often enjoy comparable precision as the ML estimates. We apply our methods to the analysis of comorbid symptoms in the Obsessive Compulsive Disorder study. Our models' random effects structure has more straightforward interpretation than those of competing methods, thus should usefully augment tools available for latent class analysis of multilevel data.

Diesel spray mixing limited vaporization with non-ideal and multi-component fuel thermophysical property effects

Internal combustion engines are, and will continue to be, a primary mode of power generation for ground transportation. Challenges exist in meeting fuel consumption regulations and emission standards while upholding performance, as fuel prices rise, and resource depletion and environmental impacts are of increasing concern. Diesel engines are advantageous due to their inherent efficiency advantage over spark ignition engines; however, their NOx and soot emissions can be difficult to control and reduce due to an inherent tradeoff. Diesel combustion is spray and mixing controlled providing an intrinsic link between spray and emissions, motivating detailed, fundamental studies on spray, vaporization, mixing, and combustion characteristics under engine relevant conditions. An optical combustion vessel facility has been developed at Michigan Technological University for these studies, with detailed tests and analysis being conducted. In this combustion vessel facility a preburn procedure for thermodynamic state generation is used, and validated using chemical kinetics modeling both for the MTU vessel, and institutions comprising the Engine Combustion Network international collaborative research initiative. It is shown that minor species produced are representative of modern diesel engines running exhaust gas recirculation and do not impact the autoignition of n-heptane. Diesel spray testing of a high-pressure (2000 bar) multi-hole injector is undertaken including non-vaporizing, vaporizing, and combusting tests, with sprays characterized using Mie back scatter imaging diagnostics. Liquid phase spray parameter trends agree with literature. Fluctuations in liquid length about a quasi-steady value are quantified, along with plume to plume variations. Hypotheses are developed for their causes including fuel pressure fluctuations, nozzle cavitation, internal injector flow and geometry, chamber temperature gradients, and turbulence. These are explored using a mixing limited vaporization model with an equation of state approach for thermopyhysical properties. This model is also applied to single and multi-component surrogates. Results include the development of the combustion research facility and validated thermodynamic state generation procedure. The developed equation of state approach provides application for improving surrogate fuels, both single and multi-component, in terms of diesel spray liquid length, with knowledge of only critical fuel properties. Experimental studies are coupled with modeling incorporating improved thermodynamic non-ideal gas and fuel

Caregiver Responses to the Language Mixing of a Young Trilingual

The situation once described by Hoffmann (1985), in which children grow up exposed to three languages from an early age, is a reality for an increasing number of families. In Europe – as elsewhere – greater mobility is leading to greater numbers of mixed-language couples (Piller 2002), and, by extension, multilingual families. For such families, questions concerning the acquisition and maintenance of three or more languages in a natural environment are of direct relevance. Researchers in bilingualism have already pointed out the importance of social context for the acquisition of two languages in childhood, focusing in particular on the quantity and quality of exposure to the languages (De Houwer 1990; Döpke 1992; Okita 2002; Lanza 2004) or the prestige of the languages (Lambert 1977). In this paper, I will make use of the insights gained by such researchers and test them in a trilingual setting. The paper will focus mainly on one aspect, namely the conversational style of parents and caretakers. The data come from research being carried out in Switzerland and consist of 33 interviews with multilingual families, as well as case studies of two trilingual children. The findings attest to the importance of conversational style, but at the same time indicate that a number of further factors are also of great significance.

Integrity and regeneration of mechanotransduction machinery regulate aminoglycoside entry and sensory cell death

Sound perception requires functional hair cell mechanotransduction (MET) machinery, including the MET channels and tip-link proteins. Prior work showed that uptake of ototoxic aminoglycosides (AG) into hair cells requires functional MET channels. In this study, we examined whether tip-link proteins, including Cadherin 23 (Cdh23), regulate AG entry into hair cells. Using time-lapse microscopy on cochlear explants, we found rapid uptake of gentamicin-conjugated Texas Red (GTTR) into hair cells from three-day-old Cdh23(+/+) and Cdh23(v2J/+) mice, but failed to detect GTTR uptake in Cdh23(v2J/v2J) hair cells. Pre-treatment of wildtype cochleae with the calcium chelator 1,2-bis(o-aminophenoxy) ethane-N,N,N',N'-tetraacetic acid (BAPTA) to disrupt tip-links also effectively reduced GTTR uptake into hair cells. Both Cdh23(v2J/v2J) and BAPTA-treated hair cells were protected from degeneration caused by gentamicin. Six hours after BAPTA treatment, GTTR uptake remained reduced in comparison to controls; by 24 hours, drug uptake was comparable between untreated and BAPTA-treated hair cells, which again became susceptible to cell death induced by gentamicin. Together, these results provide genetic and pharmacologic evidence that tip-links are required for AG uptake and toxicity in hair cells. Because tip-links can spontaneously regenerate, their temporary breakage offers a limited time window when hair cells are protected from AG toxicity.