ATOMIC FORCE MICROSCOPY METHOD DEVELOPMENT FOR SURFACE ENERGY ANALYSIS

The vast majority of pharmaceutical drug products are developed, manufactured, and delivered in the solid-state where the active pharmaceutical ingredient (API) is crystalline. With the potential to exist as polymorphs, salts, hydrates, solvates, and cocrystals, each with their own unique associated physicochemical properties, crystals and their forms directly influence bioavailability and manufacturability of the final drug product. Understanding and controlling the crystalline form of the API throughout the drug development process is absolutely critical. Interfacial properties, such as surface energy, define the interactions between two materials in contact. For crystal growth, surface energy between crystal surfaces and liquid environments not only determines the growth kinetics and morphology, but also plays a substantial role in controlling the development of the internal structure. Surface energy also influences the macroscopic particle interactions and mechanical behaviors that govern particle flow, blending, compression, and compaction. While conventional methods for surface energy measurements, such as contact angle and inverse gas chromatography, are increasingly employed, their limitations have necessitated the exploration of alternative tools. For that reason, the first goal of this research was to serve as an analytical method development report for atomic force microscopy and determine its viability as an alternative approach to standard methods of analysis. The second goal of this research was to assess whether the physical and the mathematical models developed on the reference surfaces such as mica or graphite could be extended to organic crystal surfaces. This dissertation, while dependent upon the requisite number of mathematical assumptions, tightly controlled experiments, and environmental conditions, will nonetheless help to bridge the division between lab-bench theory and successful industrial implementation. In current practice, much of pharmaceutical formulation development relies on trial and error and/or duplication of historical methods. With a firm fundamental understanding of surface energetics, pharmaceutical scientists will be armed with the knowledge required to more effectively estimate, predict, and control the physical behaviors of their final drug products

CHEMOMETRICS, SPECTROMETRY, AND SENSORS FOR INTEGRATED SENSING AND PROCESSING: ADVANCING PROCESS ANALYTICAL TECHNOLOGY

The research contained in the following dissertation spans a diverse range of scientific scholarship, including; chemometrics for integrated sensing and processing (ISP), near infrared and acoustic resonance spectrometry for analyte quantification and classification, and an ISP acoustic sensor as an alternative to conventional acoustic spectrometry. These topics may at first seem disjointed; however, closer inspection reveals that chemometrics, spectrometry, and sensors taken together form the umbrella under which applied spectrometry and analytical chemistry fall. The inclusion of each of these three serves to paint the complete portrait of the role of applied spectrometry for the advancement of process analytical technology. To illustrate the totality of this portrait, this research seeks to introduce and substantiate three key claims. (1) When applicable, optical spectrometry and acoustic spectrometry are preferred alternatives to slower and more invasive methods of analysis. (2) Chemometrics can be implemented directly into the physical design of spectrometers, thus sparing the need for computationally demanding post-collection multivariate analyses. (3) Using this principle, ISP sensors can be developed specifically for use in highly applied situations, making possible automatic analyte quantification or classification without the computational burden and extensive data analysis typically associated with conventional spectrometry. More concisely, these three claims can be stated as follows: spectrometry has a broad range of uses, chemometrics for ISP makes spectrometry more efficient, and for all analytical problems with a spectrometric solution, an ISP sensor, specifically tailored to the needs of the experiment, can more effectively solve the same analytical problem

Adventurous Tales: Stories of the Sea and the City by Victor-Emile Michelet; A selection, translated with an introduction.

Arts and Ideas in the HumanitiesRomance Languages and Literatureshttp://deepblue.lib.umich.edu/bitstream/2027.42/85303/1/ejebbers.pd

A Positive Project Outcome: Lessons from a Non-Dominant Government University-Based Program

This article explores factors contributing to a non-dominant collaboration paradigm in a partnership between a government-based international development agency and a university-based non-governmental organization. Anchored in Wood’s and Gray’s collaborative framework, this article describes how the steeply hierarchical partnership navigated the elements of collaboration – organizational autonomy; shared problem domain; interactive processes; shared rules, norms, and structures; and decision making – to produce non-dominant values and practices deriving from negotiated processes, rules, norms, and structures that produced positive collaboration outcomes. In particular, a history of prior mutually beneficial interactions emerges as a critical precondition for achieving a non-dominant collaboration in this case study’s steeply hierarchical organizational relationship, one in which egalitarianism and equal decision-making regarding the agenda and the goals of the collaboration could have been highly constrained

Magneto-vestibular Stimulation (MVS): effects on behaviour and resting state networks

The MRI environment can stimulate the balance sensors within the inner ear. This is known as magnetovestibular stimulation (MVS), which occurs within the inner ear. It arises because of biophysical interactions between the fluids within our inner ear, the balance sensors and the magnetic field within an MRI machine. This vestibular system usually deteriorates with aging and is commonly dysfunctional in disorders like Parkinson\u27s and Alzheimer\u27s and following concussions and strokes.https://ir.lib.uwo.ca/brainscanprojectsummaries/1012/thumbnail.jp

Testing Born's Rule in Quantum Mechanics with a Triple Slit Experiment

In Mod. Phys. Lett. A 9, 3119 (1994), one of us (R.D.S) investigated a formulation of quantum mechanics as a generalized measure theory. Quantum mechanics computes probabilities from the absolute squares of complex amplitudes, and the resulting interference violates the (Kolmogorov) sum rule expressing the additivity of probabilities of mutually exclusive events. However, there is a higher order sum rule that quantum mechanics does obey, involving the probabilities of three mutually exclusive possibilities. We could imagine a yet more general theory by assuming that it violates the next higher sum rule. In this paper, we report results from an ongoing experiment that sets out to test the validity of this second sum rule by measuring the interference patterns produced by three slits and all the possible combinations of those slits being open or closed. We use attenuated laser light combined with single photon counting to confirm the particle character of the measured light.Comment: Submitted to the proceedings of Foundations of Probability and Physics-5, Vaxjo, Sweden, August 2008. 8 pages, 8 figure

The curious nonexistence of Gaussian 2-designs

2-designs -- ensembles of quantum pure states whose 2nd moments equal those of the uniform Haar ensemble -- are optimal solutions for several tasks in quantum information science, especially state and process tomography. We show that Gaussian states cannot form a 2-design for the continuous-variable (quantum optical) Hilbert space L2(R). This is surprising because the affine symplectic group HWSp (the natural symmetry group of Gaussian states) is irreducible on the symmetric subspace of two copies. In finite dimensional Hilbert spaces, irreducibility guarantees that HWSp-covariant ensembles (such as mutually unbiased bases in prime dimensions) are always 2-designs. This property is violated by continuous variables, for a subtle reason: the (well-defined) HWSp-invariant ensemble of Gaussian states does not have an average state because the averaging integral does not converge. In fact, no Gaussian ensemble is even close (in a precise sense) to being a 2-design. This surprising difference between discrete and continuous quantum mechanics has important implications for optical state and process tomography.Comment: 9 pages, no pretty figures (sorry!

A Randomized, Controlled, Phase 2 Study of Maralixibat in the Treatment of Itching Associated With Primary Biliary Cholangitis.

Primary biliary cholangitis (PBC) is typically associated with elevated serum bile acid levels and pruritus, but pruritus is often refractory to treatment with existing therapies. This phase 2 study assessed the efficacy and safety of maralixibat, a selective, ileal, apical, sodium-dependent, bile acid transporter inhibitor, in adults with PBC and pruritus. Adults with PBC and pruritus who had received ursodeoxycholic acid (UDCA) for ≥6 months or were intolerant to UDCA were randomized 2:1 to maralixibat (10 or 20 mg/day) or placebo for 13 weeks in combination with UDCA (when tolerated). The primary outcome was change in Adult Itch Reported Outcome (ItchRO™) average weekly sum score (0, no itching; 70, maximum itching) from baseline to week 13/early termination (ET). The study enrolled 66 patients (maralixibat [both doses combined], n = 42; placebo, n = 24). Mean ItchRO™ weekly sum scores decreased from baseline to week 13/ET with maralixibat (-26.5; 95% confidence interval [CI], -31.8, -21.2) and placebo (-23.4; 95% CI, -30.3, -16.4). The difference between groups was not significant (P = 0.48). In the maralixibat and placebo groups, adverse events (AEs) were reported in 97.6% and 70.8% of patients, respectively. Gastrointestinal disorders were the most frequently reported AEs (maralixibat, 78.6%; placebo, 50.0%). Conclusion: Reductions in pruritus did not differ significantly between maralixibat and placebo. However, a large placebo effect may have confounded assessment of pruritus. Lessons learned from this rigorously designed and executed trial are indispensable for understanding how to approach trials assessing pruritus as the primary endpoint and the therapeutic window of bile acid uptake inhibition as a therapeutic strategy in PBC