Avalanche: Architecture of Emergency

A buildign for rescue must perform its function seamlessly during times of emergency. The consideration of landscape in terms of an event leads to an evocative solution that best accommodates the program of the project. Using a thorough investigation of spatial, infrastructural, and conceptual networks on the site, I will design a center for avalanche rescue in the White Mountains of New Hampshire

Implementation of a multiblock sensitivity analysis method in numerical aerodynamic shape optimization

A multiblock sensitivity analysis method is applied in a numerical aerodynamic shape optimization technique. The Sensitivity Analysis Domain Decomposition (SADD) scheme which is implemented in this study was developed to reduce the computer memory requirements resulting from the aerodynamic sensitivity analysis equations. Discrete sensitivity analysis offers the ability to compute quasi-analytical derivatives in a more efficient manner than traditional finite-difference methods, which tend to be computationally expensive and prone to inaccuracies. The direct optimization procedure couples CFD analysis based on the two-dimensional thin-layer Navier-Stokes equations with a gradient-based numerical optimization technique. The linking mechanism is the sensitivity equation derived from the CFD discretized flow equations, recast in adjoint form, and solved using direct matrix inversion techniques. This investigation is performed to demonstrate an aerodynamic shape optimization technique on a multiblock domain and its applicability to complex geometries. The objectives are accomplished by shape optimizing two aerodynamic configurations. First, the shape optimization of a transonic airfoil is performed to investigate the behavior of the method in highly nonlinear flows and the effect of different grid blocking strategies on the procedure. Secondly, shape optimization of a two-element configuration in subsonic flow is completed. Cases are presented for this configuration to demonstrate the effect of simultaneously reshaping interfering elements. The aerodynamic shape optimization is shown to produce supercritical type airfoils in the transonic flow from an initially symmetric airfoil. Multiblocking effects the path of optimization while providing similar results at the conclusion. Simultaneous reshaping of elements is shown to be more effective than individual element reshaping due to the inclusion of mutual interference effects

Shape optimization of single- and two-element airfoils on multiblock grids

A multiblock, discrete sensitivity analysis method is used to couple a direct optimization method and a flow analysis method. The domain is divided into smaller subdomains for which the sensitivities are obtained separately. Then, an effective sensitivity equation is solved to complete the coupling of all the sensitivity information. The flow analysis is based on the thin-layer Navier-Stokes equations solved by an implicit, upwind-biased, finite-volume method. The method of feasible directions is used for the present gradient-based optimization approach. First, a transonic airfoil is optimized to investigate the behavior of the method in highly nonlinear flows as well as the effect of different blocking strategies on the procedure. A supercritical airfoil is produced from an initially symmetric airfoil with multiblocking affecting the path but not the final shape. Secondly, a two-element airfoil is shape optimized in subsonic flow to demonstrate the present method's capability of shaping aerodynamically interfering elements simultaneously. For a very low and a very high Reynolds number cases, the shape of the main airfoil and the flap are optimized to yield improved lift-to-drag ratios

A hierarchical, fuzzy inference approach to data filtration and feature prioritization in the connected manufacturing enterprise

In manufacturing, the technology to capture and store large volumes of data developed earlier and faster than corresponding capabilities to analyze, interpret, and apply it. The result for many manufacturers is a collection of unanalyzed data and uncertainty with respect to where to begin. This paper examines big data as both an enabler and a challenge for the connected manufacturing enterprise and presents a framework that sequentially tests and selects independent variables for training applied machine learning models. Unsuitable features are discarded, and each remaining feature receives a crisp numeric output and a linguistic label, both of which are measures of the feature’s suitability. The framework is tested using three datasets employing time series, binary, and continuous input data. Results of filtered models are compared to results obtained by base, unfiltered sets of features using a proposed metric of performance-size ratio. Framework results outperform base feature sets in all tested cases, and the proposed future research will be to implement it in a case study in the electronic assembly manufacture

Mammary cell activity and turnover in dairy cows treated with the prolactin-release inhibitor quinagolide and milked once daily

To assess the regulation of mammary cell activity, survival, and proliferation by prolactin (PRL), 5 Holstein cows in early lactation received daily i.m. injections of 1 mg of quinagolide, a suppressor of PRL release, for 9 wk, whereas 4 control cows received the vehicle (water) only. During the last week of treatment, one udder half was milked once a day (1×) and the other twice a day (2×). Mammary biopsies were harvested 1 wk before and 4 and 8 wk after the start of quinagolide treatment. The quinagolide injections reduced milk yield and resulted in lower levels of κ-casein and α-lactalbumin mRNA in the mammary biopsies at wk 4 compared with the control cows. In the mammary tissue of the quinagolide-treated cows at wk 8 of treatment, cell proliferation (as determined by proliferating cell nuclear antigen labeling) was lower and apoptosis (as determined by the terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling assay) was higher than in the mammary tissue of the control cows. During differential milking, mammary epithelial cells (MEC) were extracted from the milk by centrifugation and purified by immunocytochemical binding to allow variations in the levels of mammary transcripts to be observed. After 9 wk of treatment, levels of α-lactalbumin and κ-casein mRNA were lower in the MEC isolated from milk of the quinagolide-treated cows. This effect was associated with lower PRL receptor mRNA levels and a tendency toward lower viability in the milk-isolated MEC from the 2×-milked glands. The decrease from 2× milking to 1× milking also downregulated α-lactalbumin and κ-casein transcripts in the milk-isolated MEC. Viability was higher for the MEC collected from the 1×-milked udder halves compared with the 2×-milked halves. In conclusion, the reduction in milk yield after chronic administration of the PRL-release inhibitor quinagolide is associated with a reduction in mammary cell activity, survival, and proliferation in lactating dairy cows. Reduced milking frequency was also associated with a decrease in MEC activity

Investigating the Structure of Potential New Drug to Treat Sickle Cell Anemia through Inhibition of the Polymerization of Hemoglobin S​

Sickle cell anemia is a hematologic disorder impacting over 15 million people worldwide. It is caused by a single point mutation in the gene hemoglobin-Betha, where a glu group is replaced by val (GAG --- GTG) in the seventh codon (glu7val) of chromosome 1. In this study, we are comparing the anti-sickling properties of drugs in varied conditions in order to create a drug that is effective in an O2-independent manner and with a 1:1 stoichiometry for lower dosage purposes. We used Pymol and Jmol to compare the structures of the aldehydes GBT-440 and VZHE-039, which interact on the same binding site to treat sickle cell disease. GBT-440’s bulkiness allows it to have a 1:1 stoichiometry, while VZHE-039’s solubility is due to its interaction with the hemoglobin’s alpha cleft, allowing it to be O2-independent. We identified the pyridine and pyrazole structure from GBT-440 and the methyl hydroxy moite from VZHE-039 as key structures, and created a hypothetical new drug, a hybrid of VZHE-039 and GBT-440. The pose predicted would allow the drug to interact with the sickled hemoglobin in a 1 to 1 ratio and in an O2-independent manner.https://nsuworks.nova.edu/protein_modeling_reports/1002/thumbnail.jp

Adhesion-independent synergy of monocytes and endothelial cells in cytokine production: regulation of IL-6 and GM–CSF production by PAF

Co-Cultures of monocytes (MO) and endothelial cells (EC) were studied for their capacity to synergize in the production of interleukin-6 (IL-6) and granulocyte-macrophage colony-stimulating factor (GM–CSF), two cytokines potentially important in vascular physiopathology. Resting monocytes produced detectable amounts of IL-6 but no GM–CSF, whereas confluent EC produced significant quantities of GM–CSF, but minimal IL-6. In co-cultures without stimuli, additive synthesis of both cytokines was observed. When EC were pretreated, however, with either PAF, TNF or both stimuli, before addition of MO, synergistic production of IL-6 was observed. In contrast, GM–CSF production was not enhanced by coculture of monocytes with activated EC. When either cell population was fixed with paraformaldehyde or killed by freeze-thawing before addition to the co-culture, cytokine levels reverted to those produced by the unaffected population alone. On the other hand, separating the two cell populations by a cell-impermeable membrane in transwell cultures did not affect the synergistic production of the cytokines. Taken together, our data suggest that EC and MO can synergize in response to stimuli by producing IL-6 and that this synergy is dependent on the integrity of both cell populations, but independent of cell-cell contact

The effects of endogenous and exogenous gonadal hormones on spatial navigation in women and in female rats.

Gonadal hormones, both endogenous and exogenous, are implicated in cognition. Yet, the role of gonadal hormones in spatial navigation remains relatively unexplored. While navigating a maze either place memory or response memory can be used. The gonadal hormone 17β-estradiol affects which memory system female rats use during navigation, thus producing a memory bias. Across the menstrual cycle, women's memory bias is also altered. This thesis examined the role of endogenous and exogenous hormones in spatial navigation in both female rats and in women. It was shown that the endogenous hormone, progesterone promoted the use of response memory in females. It was also shown that the exogenous hormones used in hormonal contraceptives impact memory bias in females. However, the impact of these hormones on spatial navigation was different in rats than what was observed in humans. It was also shown that both endogenous and exogenous hormones have different effects depending on whether they are administered alone or in combination. Both endogenous and exogenous gonadal hormones are involved in memory bias during spatial navigation in females