Structural Studies of Bile Salt Aggregation by Nuclear Magnetic Resonance Spectroscopy and Mass Spectrometry

Bile salts are biomolecules that are produced in the liver and are responsible for a range of functions in the process of digestion, primarily the emulsification of dietary fat and fat-soluble vitamins. Despite their importance in biological chemistry, the structure and dynamics of bile salt aggregation are not well understood. The efforts described herein attempt to enhance the understanding of cholate aggregation numbers (AN), critical micelle concentration (CMC), micellar structure(s), and interactions with a binaphthyl probe molecule. Cholate is the most common bile salt in mammals and is, therefore, a decent model for describing bile salt aggregation. CMC determination is achieved by observing the 1H NMR chemical shift perturbation of 1,1’-binaphthyl-2,2’-diyl hydrogen phosphate (R,S-BNDHP), a probe molecule for bile salt aggregation, when exposed to increased concentrations of sodium cholate. Using NMR and a phase-transition model to determine CMCs for pH 12.0 sodium cholate results in the observation of three unique CMC values at 6.1, 11.0, and ~25 mM. Using 1H-13C heteronuclear single quantum coherence (HSQC) spectroscopy, a two-dimensional NMR experiment, it appears that anti-parallel cholate dimers are not strictly collinear, but rather a skew exists between the two-cholate monomers. The existence of a skew is surprising as it would be incongruent with a well-known model of bile salt aggregation proposed by Donald Small proposed in 1968. HSQC also showed evidence that R- and S-BNDHP attack different edges of a cholate aggregate, possibly explaining the chiral selectivity exhibited by sodium cholate aggregates in earlier micellar electrokinetic chromatography experiments and confirming previous two-dimensional nuclear Overhauser effect (NOE) NMR data. HSQC data also suggest evidence for the interactions responsible for the aggregation of predicted aggregates by Small’s model. High-resolution negative ion electrospray ionization mass spectrometry (ESI-MS) data suggest that cholate is capable of forming several aggregates of sufficient stability for mass analysis, the most massive of which is an aggregate with an aggregation number of 18. With these data it is clear that this system has several complexities that affect aggregation that may not be accounted for in previous bile salt aggregation models

An investigation into the effectiveness of PDF/X premedia workflows

PDF/X technology was introduced in the mid 90\u27s with the intentions of improving and automating the prepress workflows. Standards committees such as CGATS (Committee for Graphic Arts Technical Standards) and DDAP (Digital Distribution of Advertisers for Publications) started to draft and implement a plan of action to succeed the current file formats being used in premedia workflows. Previous file submissions that were handed off from advertising and design agencies became too time-consuming to prepare them for the final run. Top-tier printing and publishing companies such as RR Donnelley, Quad Graphics, Vertis, and Time Inc, started to invest in new technology integration in order to improve efficiency and automate the production workflow for publications and advertisements. Recently, the committees have finished and received approval on 2/3rds of the intended outline for ISO 15930: 2003 Standards for Graphic Technology - - Prepress digital data exchange - - for the use of PDF.1 PDF/X-1a and X-3 have been approved as standards and solutions for the publication and commercial printing markets. PDF/X-2 is still in the process of finalization, but will be beneficial mostly to catalog and commercial printing. The goal of these standards is to provide an efficient vehicle for exchanging raster and vector data for print production within the graphic arts industry. The intent was for the sender and the receiver of PDF/X files to use applications that have the same level of compliance. Therefore, digital data workflows could be processed seamlessly between these channels of communication without any surprises. This would change premedia operations and bridge the communication gap between the customer (agency, designer) and the service provider (prepress, publisher), eliminating any variables or errors. This new workflow is still a mystery to many. Only the larger companies that have already invested in this new technology are truly knowledgeable about it. With this transition taking place, a greater percentage medium-sized plant in the $2 million to 5 million-range plan to start investing in Portable Document Format (PDF) workflow solutions than other size-shops.2 The purpose of this thesis is measure the current PostScript workflow that the majority of premedia industry currently uses versus the new PDF/X workflow solution created to reduce the steps in current premedia operation. Most importantly, this will result in a new model based on PDF/X technology for mid-sized companies to invest in, that promises a high return-on-investment. Premedia operations are usually responsible for 20-25% of the overall selling costs according to 2002 PIA Ratios. Due to the variety of difficulties encountered in current premedia workflows, this model will be developed to decrease production time and costs. Within the first half of the study, data will be collected through measurement and visual assessment to evaluate the performance and functionality of both premedia operations. In the other half of this study, subjective testing will address the issues of raster image processing time and a reduction of storage requirements

The microbiological and chemical composition of baled and precision-chop silages on a sample of farms in County Meath

peer-reviewedA Teagasc Walsh Fellowship awarded to J. McEniry supported this study.Baled and precision-chop silages were examined on a sample of farms in the Irish midlands to determine microbiological and chemical composition at feedout. Silage making practices and chemical composition were similar to those in national surveys. Wilting was an integral part of baled silage production and was reflected in a more restricted fermentation (higher pH and water-soluble carbohydrates, with lower fermentation acids and buffering capacity) compared to precision-chop silage. Yeast numbers were higher in baled silage, suggesting a more aerobic environment within the bale. Although the fermentation appeared similar in the outer and inner horizons of baled silage, yeast, lactic acid bacteria and Enterobacteria numbers were higher in the outer horizon suggesting less exacting anaerobiosis adjacent to the surface of the bale

Manipulating the ensilage of wilted, unchopped grass through the use of additive treatments

peer-reviewedBaled silage composition frequently differs from that of comparable conventional precision-chop silage. The lower final concentration of fermentation products in baled silage makes it more conducive to the activities of undesirable microorganisms. Silage additives can be used to encourage beneficial microbial activity and/or inhibit detrimental microbial activity. The experiment was organised in a 2 (chop treatments) × 6 (additive treatments) × 2 (stages of ensilage) factorial arrangement of treatments (n = 3 silos/treatment) to suggest additive treatments for use in baled silage production that would help create conditions more inhibitory to the activities of undesirable microorganisms and realise an outcome comparable to precision-chop silage. Chopping the herbage prior to ensiling, in the absence of an additive treatment, improved the silage fermentation. In the unchopped herbage, where the fermentation was poorer, the lactic acid bacterial inoculant resulted in an immediate increase (P < 0.001) in lactic acid concentration and a faster decline (P < 0.001) in pH with a subsequent reduction in butyric acid (P < 0.001) and ammonia-N (P < 0.01) concentrations. When sucrose was added in addition to the lactic acid bacterial inoculant, the combined treatment had a more pronounced effect on pH, butyric acid and ammonia-N values at the end of ensilage. The formic acid based additive and the antimicrobial mixture restricted the activities of undesirable microorganisms resulting in reduced concentrations of butyric acid (P < 0.001) and ammonia-N (P < 0.01). These additives offer a potential to create conditions in baled silage more inhibitory to the activities of undesirable microorganisms.A Teagasc Walsh Fellowship Research Scholarship awarded to J. McEniry supported this study

Black Swans and Retirement Strategies: Is “Buy and Hold Best”?

The recent market crash which has led to as much as a 47% drop in the value of the S&P500 index has made some of us wonder if there is a cost effective way for us to hedge our retirement portfolios against such a drastic loss. Our objective is to investigate empirically the tradeoffs that will arise from using a protective put strategy for hedging retirement portfolios over an investment horizon that is long enough to be comparable to the average holding period for retirement portfolio

What Financial Risk Managers Can Learn from Six Sigma Quality Programs

As the financial crisis of 2008 has revealed, there are some flaws in the models used by financial firms to assess risk. Credit, volatility, and liquidity risk were all inadequately modeled by supposedly sophisticated financial institutions employing dozens of financial engineers with advanced degrees. It is now clear that some of the underlying assumptions of the statistical models utilized were seriously flawed, and interactive and systemic effects were improperly modeled. Correcting these modeling flaws is one approach to preventing a reoccurrence. However, another approach is suggested by Six Sigma quality programs used in manufacturing and service industries. Some basic tenets of the Six Sigma programs are directly applicable to improving risk management in financial firms and in portfolio design. These include the features of over-engineering, robust design, and reliability engineerin

Using machine learning techniques to automate sky survey catalog generation

We describe the application of machine classification techniques to the development of an automated tool for the reduction of a large scientific data set. The 2nd Palomar Observatory Sky Survey provides comprehensive photographic coverage of the northern celestial hemisphere. The photographic plates are being digitized into images containing on the order of 10(exp 7) galaxies and 10(exp 8) stars. Since the size of this data set precludes manual analysis and classification of objects, our approach is to develop a software system which integrates independently developed techniques for image processing and data classification. Image processing routines are applied to identify and measure features of sky objects. Selected features are used to determine the classification of each object. GID3* and O-BTree, two inductive learning techniques, are used to automatically learn classification decision trees from examples. We describe the techniques used, the details of our specific application, and the initial encouraging results which indicate that our approach is well-suited to the problem. The benefits of the approach are increased data reduction throughput, consistency of classification, and the automated derivation of classification rules that will form an objective, examinable basis for classifying sky objects. Furthermore, astronomers will be freed from the tedium of an intensely visual task to pursue more challenging analysis and interpretation problems given automatically cataloged data

A Combined WiMAX/DSRC Approach to Vehicular Networking

From wireless Internet access at cafes to the expanding popularity of smart phones, ubiquitous Internet access has generated much public demand and research. Supplying broadband Internet access for in-vehicle applications is a research area still in its infancy. This thesis examines the strengths and weaknesses of WiMAX and DSRC, two protocols that have been central in much of the research surrounding in-vehicle network access. The thesis then proposes a novel system structure that combines both of these technologies and adds a network access layer in order to provide a system structure that offers high bandwidth, bounded latency and robust support for the high levels of mobility experienced by vehicle-based users. This provides the network support for applications such as streaming audio, video and Voice over IP. The thesis also describes a demonstration system that partly implements the proposed system structure