CHRYSANTHEMUM PRODUCTION PLANNING UNDER TIME-TO-HARVEST UNCERTAINTY

Crop Production/Industries,

Design and performance of felodipine-based solid dispersions

In recent years the pharmaceutical industry has seen a rise in the number of drug compounds with low aqueous solubility, and consequently poor oral bioavailablility. One potential solution to this problem is to formulate such compounds as solid dispersions, whereby the drug is dispersed in a carrier matrix in the solid state. In this thesis, the hypothesis that a number of drug-drug and drug-polymer intermolecular interactions influence the physical stability and dissolution performance of solid dispersions is considered. The aim is to use correlations between drug molecular structure and solid dispersion performance to develop a platform to rapidly assess whether drug compounds will have favourable properties when formulated as a solid dispersion. Amorphous felodipine/copovidone solid dispersions are used as a model system to develop a suitable testing regime with regards to physical stability and dissolution performance. A laser light scattering technique developed in this work shows that morphological changes in felodipine/copovidone films exposed to water are due to polymer swelling. A combination of dissolution testing methodologies is also used to suggest a mechanism for the dissolution of bulk solid dispersion samples. Contributions of individual functional groups in the felodipine analogues to the physical stability and dissolution performance of their amorphous solid dispersions are assessed. Blocking of the felodipine amine hydrogen-bond-donor with an N-methyl, and the removal of chlorine substituents are both shown to reduce the physical stability of the solid dispersions. Correlations between molecular descriptors and data from the above experiments show that drug compounds are more likely to crystallise from solid dispersions with copovidone if they have a low log P, low relative molecular mass and low polarizability. Such correlations can form the basis of a screening method for the molecular design of analogous drug compounds likely to form high-performance solid dispersions with copovidone

Comparison of interactions between beta-hairpin decapeptides and SDS/DPC micelles from experimental and simulation data

<p>Abstract</p> <p>Background</p> <p>We applied a combined experimental and computational approach to ascertain how peptides interact with host and microbial membrane surrogates, in order to validate simulation methodology we hope will enable the development of insights applicable to the design of novel antimicrobial peptides. We studied the interactions of two truncated versions of the potent, but cytotoxic, antimicrobial octadecapeptide protegrin-1, PC-72 [LCYCRRRFCVC] and PC-73 [CYCRRRFCVC].</p> <p>Results</p> <p>We used a combination of FTIR, fluorescence spectroscopy and molecular dynamics simulations to examine the peptides' interactions with sodium dodecylsulfate (SDS) and dodecylphosphocholine (DPC) micelles. The relative amounts of secondary structure determined by FTIR agreed with those from the simulations. Fluorescence spectroscopy, deuterium exchange experiments and the simulations all indicate that neither peptide embeds itself deeply into the micelle core. Although molecular simulations placed both peptides at the micelle-water interface, further examination revealed differences in how certain residues interacted with the micelle core.</p> <p>Conclusion</p> <p>We demonstrate here the accuracy of molecular dynamics simulations methods through comparison with experiments, and have used the simulation results to enhance the understanding of how these two peptides interact with the two types of micelles. We find agreement between simulation and experimental results in the final structure of the peptides and in the peptides final conformation with respect to the micelle. Looking in depth at the peptide interactions, we find differences in the interactions between the two peptides from the simulation data; Leu-1 on PC-72 interacts strongly with the SDS micelle, though the interaction is not persistent – the residue withdraws and inserts into the micelle throughout the simulation.</p

COMPARING JUDGMENT AND TEMPORAL EVOLUTION OF TRUST BETWEEN ARTIFICIAL INTELLIGENCE SUPPORTED DECISION-MAKING AND HUMAN SUPPORTED DECISION-MAKING

Decision support systems underpin the Department of Defense’s Command and Control apparatus, feeding into decision-making processes at all levels. The extant research surrounding Artificial Intelligence’s (AI’s) use in decision support systems establishes trust as a critical driver of such systems’ performance and adoption. However, little research has explored the impacts of temporal factors and the existence of intermediate decisions on a decision-maker’s level of trust in such systems or how the impacts differ when the decision is supported by another human versus an AI. Extant literature assumes trust in AI is different than other objects of trust. This thesis explores this assumption by asking whether the emergence of trust depends more on the object or source of trust. A previous experiment examined the impacts of time and intermediate judgements on trust when the decision support was provided by an AI-system only. This thesis extends that experiment by also manipulating the source of the decision-support, to be human, not just AI. By including the base case of human-to-human trust, this research enables comparative analysis regarding the relative impact of intermediate judgments and time on trust in decision-support systems.Distribution Statement A. Approved for public release: Distribution is unlimited.Outstanding ThesisMajor, United States Marine CorpsMajor, United States Marine Corp

Findings of the International Subarachnoid Aneurysm Trial and the National Study of Subarachnoid Haemorrhage in context.

Concern has been expressed about the applicability of the findings of the International Subarachnoid Aneurysm Trial (ISAT) with respect to the relative effects on outcome of coiling and clipping. It has been suggested that the findings of the National Study of Subarachnoid Haemorrhage may have greater relevance for neurosurgical practice. The objective of this paper was to interpret the findings of these two studies in the context of differences in their study populations, design, execution and analysis. Because of differences in design and analysis, the findings of the two studies are not directly comparable. The ISAT analysed all randomized patients by intention-to-treat, including some who did not undergo a repair, and obtained the primary outcome for 99% of participants. The National Study only analysed participants who underwent clipping or coiling, according to the method of repair, and obtained the primary outcome for 91% of participants. Time to repair was also considered differently in the two studies. The comparison between coiling and clipping was susceptible to confounding in the National Study, but not in the ISAT. The two study populations differed to some extent, but inspection of these differences does not support the view that coiling was applied inappropriately in the National Study. Therefore, there are many reasons why the two studies estimated different sizes of effect. The possibility that there were real, systematic differences in practice between the ISAT and the National Study cannot be ruled out, but such explanations must be seen in the context of other explanations relating to chance, differences in design or analysis, or confounding

Sesame (Sesamum indicum) Response to Postemergencedirected Herbicide Applications

Field studies were conducted from 2006 to 2010 under weed-free conditions in south Texas and in the Texas High Plains to determine sesame tolerance to applied postemergence-directed herbicides. Injury was greatest when herbicides were applied to 15 cm of the main stem compared to herbicide applications made to 5 cm of the main stem height. Glyphosate at 0.84 kg ae/ha and pyrithiobac-sodium at 0.07 kg ai/ha resulted in the greatest sesame stunting (28–90%) when applied up to 15 cm main stem height, while carfentrazone-ethyl, flumioxazin, and imazethapyr caused greatest injury when applied to 5 cm of the main stem. When glyphosate was applied up to 5 cm main stem height, sesame injury was 20% or less. Glyphosate applied up to the 15 cm stem height and pyrithiobac-sodium applied 5 and 15 cm stem height consistently reduced sesame yield when compared with the nontreated control. Acetochlor, diuron, fluometuron, and prometryn did not cause any sesame stunting. Carfentrazone-ethyl, diuron, flumioxazin, imazethapyr, propazine, pyraflufen-ethyl, linuron, and linuron plus diuron reduced sesame yield in at least one year in south Texas