Running performance has increased immensely during the last few years, coinciding with multiple shattered world records in relatively short amount of time. Improvements in footwear material and design are likely reasons for this increase in running performance. Previous studies on the effect of footwear on running economy (RE), a determinant of running performance, have not included participant-blinding. Furthermore, they have yet to compare multiple carbon-fiber plated running shoes available for purchase, what differences there are across price ranges and shoe categories, and if there is such a thing as a placebo-effect. Aim: (1) Descriptively compare a set of heterogeneous running shoes, with regards to running economy, Foot Strike Type (FST), vertical oscillation, ground contact time, stride length and cadence; including (2) a ‘sham’ and ‘normal condition’ of the same running shoe model; and (3) explore the participant’s perception of the study-specific blinding protocol. Method: A Single Subject Experimental Study (N=1), comparing nine different shoe conditions using a crossover design. The assessment of RE was conducted using indirect calorimetry with mixing-chamber in a climate-controlled facility. Spatiotemporal parameters were assessed using a Garmin HRM-Run™, and foot strike type was visually assessed using a frame-by-frame approach based on 2D-video at 240 fps. Results: The average running economy across all shoe tests varied between 16.02 to 17.02 W/kg, with the ‘worst’ shoe costing 6.24% W/kg more than the ‘best’ shoe. The descriptive difference between the ‘sham’ and ‘normal condition’ were negligible and within the range of measurement error. Spatiotemporal parameters were overall descriptively similar between the shoes, with a few outliers who differed with regards to measure of central tendency or dispersion. FST differed between the shoes including the ‘sham’ and ‘normal condition’, but were overall consistent with the participant’s habitual FST. The study-specific blinding procedure was perceived to work well, but may also be improved in some remarks. Conclusion: Descriptive difference in some, but not all, physiological and biomechanical parameters were observed between the shoe conditions in this study, including the ‘sham’ and ‘normal condition’. Blinding procedures in experimental footwear research may be feasible and adopted with future studies.

Thesis advisor: Shih-Yuan Liu / Despite extensive research in B–N-containing aromatic systems (most notably 1,2-azaborines) for their potential use in biomedicine and materials science, development of their oxygen counterparts, 1,2-oxaborines, remains underdeveloped. Presented herein is a straightforward route to access 1,2-oxaborines via a ring-closing metathesis strategy. Attempts to utilize the 1,2-oxaborine as a 1,3-diene in the Diels–Alder cycloaddition for potential application as a 4C + 1O synthon are also presented. Lastly, investigations regarding the aromaticity of the B–O heterocycles is probed using computations and isothermal reaction calorimetry. / Thesis (MS) — Boston College, 2017. / Submitted to: Boston College. Graduate School of Arts and Sciences. / Discipline: Chemistry.

The 2-His-1-carboxylate facial triad is a common metal binding motif among nonheme iron(II) enzymes. Made up of two histidine side chain residues, and one carboxylate side chain of either a glutamate or aspartate residue occupying one face of the iron(II) octahedral coordinating sphere, the 2-His-1-carboxylate motif provides proximity of substrate(s) and molecular oxygen for important oxidation reactions in biological chemistry. Computational, structural, and kinetic analyses have afforded mechanistic details on how these enzymes control the oxidation reactions they catalyze; from the oxidation state of the metal center to the supporting interactions from secondary sphere amino acid residues. However, the extensive literature on the 2-His-1-carboxylate facial triad enzymes currently contains deficiencies in the area of fundamental, experimental thermodynamic analyses of metal and substrate binding in these systems. The focus of this study is to determine the energetics of substrate and metal binding to two representative enzymes of the 2-His-1-carboxylate facial triad-containing family. More specifically, we examine iron(II) binding to the alpha-ketoglutarate- dependent model system alpha-ketoglutarate/taurine dioxygenase, and substrate binding to a well-known extradiol dioxygenase, homoprotocatechuate 2,3-dioxygenase. Using isothermal titration calorimetry, we are able to determine equilibrium constants, enthalpies, entropies and Gibbs free energies for the binding reactions, affording new insight into what drives the reactions forward at the 2-His-1-carboxylate facial triad active site center.

Multilayer insulation (MLI) has been shown to be the best performing cryogenic insulation system at high vacuum (less than 10-3 torr), and is widely used on spaceflight vehicles. Over the past 50 years, many numerous investigations of MLI have yielded a general understanding of the many variables associated with MLI. MLI has been shown to be a function of variables such as warm boundary temperature, the number of reflector layers, and the spacer material in between reflectors, the interstitial gas pressure and the interstitial gas. Because conduction between reflectors increases with the thickness of the spacer material, and yet the radiation heat transfer is inversely proportional to the number of layers, it stands to reason that the thermal performance of MLI is a function of the number of layers per thickness, or layer density. Empirical equations that were derived based on some of the early tests showed that the conduction term was proportional to the layer density to a power. This power depended on the material combination and was determined by empirical test data. Many authors have graphically shown such optimal layer density, but none have provided any data at such low densities, or any method of determining this density. Keller, Cunnington, and Glassford showed MLI thermal performance as a function of layer density of high layer densities, but they didn’t show a minimal layer density or any data below the supposed optimal layer density. However, it was recently discovered by the author that by manipulating the derived empirical equations and taking a derivative with respect to layer density, a solution for on optimal layer density may be obtained. iv Several manufacturers have begun manufacturing MLI at densities below the analytical optimal density. This trend is apparently based on the theory that increased distance between layers lowers the conductive heat transfer and that there are no limitations on volume. By modifying the circumference of these blankets, the layer density can easily be varied. The most direct method of determining the thermal performance of MLI at cryogenic temperature is by evaporation (or “boil-off”) calorimetry. Several blankets were procured and tested at various layer densities by the Cryogenics Test Laboratory at NASA Kennedy Space Center. The blankets were tested over a wide range of layer densities including the analytical minimum. Several of the blankets were tested at the same insulation thickness while changing the layer density (thus a different number of reflector layers). Heat transfer optimization of the layer density of multilayer insulation systems would remove the variable of layer density from the complex method of designing such insulation systems. Since the layer density is one of the variables that in those complex equations that require more experience to understand fully grasp, this significantly simplifies the blanket design process. Additional testing was performed at various warm boundary temperatures and pressures. The testing and analysis was performed to determine thermal performance data and to simplify the analysis of cryogenic thermal insulation systems.

Previous studies of age-related differences in substrate oxidation over 24 hours and during exercise have provided divergent results, leaving it unclear how and if substrate oxidation is influenced with aging. The purpose of this study was to evaluate age-related differences in substrate oxidation during distinct periods of a 24-hr stay in a room calorimeter: over the entire 24 hours, during activities of daily living (ADLs), and during a 30-min treadmill walk (30MTW, at 1.3 m·s-1). Further, oxygen consumption transients were quantified in response to the 30MTW. Gas exchange measures were obtained during an incremental treadmill test in 9 young (28 + 3 yr) and 6 older (71 + 5 yr) healthy males to quantify VO2peak. On a separate visit, oxygen consumption (VO2) and carbon dioxide production (VCO2) were measured throughout a 24-hr stay in a whole-room calorimeter, and used to determine substrate oxidation from carbohydrate (CHO) and fat for the selected periods. Energy expenditure (EE), CHO oxidation, and fat oxidation were normalized to lean mass (kJ∙kg LM-1), determined by dual energy x-ray absorptiometry. Oxygen consumption on- (oxygen deficit, mL) and off- (rate constant for VO2 decay) transients were determined in response to the 30MTW. As expected, VO2peak (ml∙kg-1 LM∙min-1) was ~24% lower in older compared to young (p=0.021). EE (kJ∙kg LM-1) did not differ significantly by group for any period (p>0.099). Compared with young, older oxidized less CHO over 24 hr (p0.053). In contrast, during the 30MTW CHO oxidation did not differ by group (p>0.148), but older oxidized more fat per LM than young (p=0.002). The contrast in substrate selection between the lower-intensity ADLs (~16 and 20% VO2peak in young and older) and the 30MTW (~28 and 39% VO2peak in young and older) is consistent with a crossover from predominantly fat to CHO at a relatively higher VO2peak (relative to LM and %peak) in this group of relatively fit older males. Notably, when expressed as a percent of total substrate oxidation, older oxidized relatively more fat and less CHO over 24 hr (p=0.012), ADLs (p

Mixed solutions of β-lactoglobulin and anionic polysaccharides, specifically pectin, were formed into associative complexes through pH reduction from neutral conditions. Thermal treatment of these associative complexes was investigated as a function of biopolymer composition, heating conditions, pH, and ionic strength. Thermal treatment of β-lactoglobulin-pectin complexes at pH 4.5 – 5.0 was found to create protein-based particulates of consistent and narrow size distribution (diameter ~ 150 – 400 nm). These particulates were relatively stable to further pH adjustment and to high levels of salt (200 NaCl). Particle characteristics were maintained after re-suspending them in aqueous solutions after they have been either frozen or lyophilized. Thermal analysis of β- lactoglobulin-pectin complexes using calorimetry (DSC) and turbidity-temperature scanning indicated that the denaturation of β-lactoglobulin was unaffected by pectin, but protein aggregation was limited by the presence of pectin. Biopolymer particles formed using two different methods were compared: Type 1 – forming β-lactoglobulin nanoparticles by heating, then coating them with pectin; Type 2 – forming particles by heating β-lactoglobulin and pectin together. Type 2 particles had smaller diameters and had better pH and salt stability than Type 1 particles. It was proposed that Type 2 particles had a pectin-saturated surface that limited their aggregation, whereas Type 1 particles had “gaps” in the pectin surface coverage that led to greater aggregation. Finally, the possibility of controlling the size and concentration of biopolymer particles formed by heating β-lactoglobulin-pectin complexes by controlling preparation conditions was studied. Biopolymer particle size and concentration increased with increasing holding time (0 to 30 minutes), decreasing holding temperature (90 to 70 ºC), increasing protein concentration (0 to 2 wt%), increasing pH (4.5 to 5.0), and increasing salt concentration (0 to 50 mol/kg). The influence of these factors on biopolymer particle size was attributed to their impact on protein-polysaccharide interactions, protein denaturation, and protein aggregation kinetics. The knowledge gained from this study will facilitate the rational design of biopolymer particles with specific physicochemical and functional attributes that can be used in the food and other industries, e.g., for encapsulation, texture modification, optical properties modification.

Numerous biological phenomena occur as a result of macromolecular interactions. Metal-ion-biomolecule binding account for a large portion of these reactions, and unsurprisingly, a vast amount of new research in this area is constantly emerging. Gaining insight into the characteristics that define these interactions; including equilibrium fluctuations, metal center formation, global stability perturbation, cooperativity, allostery, and site-specific binding are all significant. As with all chemical reactions, biological interactions are regulated by thermodynamics; and the development of novel tools and methods by which to study these interactions becomes highly relevant. In this dissertation, three systems involving macromolecular binding are studied using well established biophysical techniques in conjunction with a critical look at appropriate uses for mathematical modeling. The first system studied is that of the serpin plasminogen activator inhibitor-1 (PAI-1). PAI-1 is a protease inhibitor that specifically effects fibrinolysis, or the process that prevents the formation of blood clots, and misregulation of this enzyme leads to uncontrollable hemorrhaging. ITC was utilized to investigate the thermodynamics of copper binding to PAI-1. Human carbonic anhydrase II (CA) was the second system investigated. Studies were conducted on zinc(II) and copper(II) binding to CA, a metalloenzyme responsible for acid-base balances in the blood and the transport of carbon dioxide. Interestingly, CA binds two copper(II) ions, one at the active site, and one at a higher affinity N-terminal site. Temperature dependent ITC, CD and GdnHCl denaturation studies were performed to explore the impact of copper(II) binding, particularly at the higher affinity N-terminal site. Finally, protein binding to inorganic gold nanoparticles (AuNPs) was investigated. AuNPS are utilized in areas of diagnostics, biological sensing and drug delivery. We studied binding of nanoparticles to a set of six biologically relevant proteins; glutathione, wild-type GB3, K19C GB3 (a variant at position 19), bovine CA, bovine serum albumin, and fibrinogen. Nanoparticle-protein binding was monitored via UV-Visible extinction and polarized resonance synchronous spectroscopy (PRS2). The UV extinction maxima wavelength shifts were fit with two models, a Langmuir isotherm model and a mass action-derived model. The models fit the data equally well, however, they predict very different Kd values, specifically for smaller sized AuNPs.

This study presents results on the use of ellipsometry as a novel probe for thin films of a diblock copolymer. Ellipsometry makes use of the change in polarisation induced upon reflection of light from a film covered substrate to enable calculation of the refractive index and thickness of the film. The infom1ation obtained in these measurements can be compared to differential scanning calorimetry, with the additional advantages that small sample volumes and slow cooling rates can be employed, and expansion coefficients can be determined. The work is presented in two parts; first crystallisation within the phase-separated domains is studied, then a morphological transition in the diblock ordering is characterised. By studying the temperature dependence of the film thickness and refractive index, crystallisation kinetics within very small volumes( 10^-10 L) of a poly (butadiene-b-ethylene oxide) diblock copolymer are measured. Through a comparison of two different PEO block lengths, a reduction in both the crystallisation and melting temperatures is demonstrated as the domain volume is decreased. Upon cooling, an additional transition is observed. We ascribe this to a morphological transition from a layer of ordered spheres to a lamellar layer at the substrate, which is consistent with a comparison between the data and simulated ellipsometry data. The sensitivity of ellipsometry makes it a well suited and versatile technique for probing thin film kinetics in diblock copolymers. / Thesis / Bachelor of Science (BSc)

No / The present study demonstrates the application of decision tree algorithms to the co-crystallization process. Fifty four (54) batches of carbamazepine–salicylic acid co-crystals embedded in poly(ethylene oxide) were manufactured via hot melt extrusion and characterized by powder X-ray diffraction, differnetial scanning calorimetry, and near-infrared spectroscopy. This dataset was then applied in WEKA, which is an open-sourced machine learning software to study the effect of processing temperature, screw speed, screw configuration, and poly(ethylene oxide) concentration on the percentage of co-crystal conversion. The decision trees obtained provided statistically meaningful and easy-to-interpret rules, demonstrating the potential to use the method to make rational decisions during the development of co-crystallization processes.

Calorimeter values were obtained for the standard enthalpy change for the following reactions at 10,25, and 40 degrees C.: 1. The dissaciation of the amino acid, glycine, in the zwitterion form (HA) to give the basic form (A-) and a proton. 2. The reactions of copper (II) ion with glycine to form the Cu gly+ and Cu (gly)2 complexes. 3. The reactions of nickel (II) ion with glycine and alanine to form Ni gly+, Ni (gly)2, Ni al+, and Ni (al)2 complexes. For calorimetric enthalpy calculations, the initial and final concentrations of all species in the calorimeter must be known; consequently, thermodynamic equilibrium constants were determined for this purpose. The equilibrium constants were calculated from measurements of pH versus the volume of standard acid or base added. Thermodynamic equilibrium constants were determined for the following types of reactions at 10, 25, and 40 degrees C.: 1. The dissociation of the acidic amino acid (H2A+) to the zwitterion (HA) and a proton for glycine and phenylalanine. 2. The dissociation of the amino acid zwitterion (HA) to the amino acid base (A-) and a proton for glycine and phenylalanine. 3. The formation of the complexes Cu gly+, and Cu (gly)2 from the reaction of copper (II) ion with glycine. 4. The formation of the complexes Ni gly+, Ni (gly)2, Ni al+, Ni (al)2, Ni Øal+, and Ni (Øal)2 from the reaction of nickel (II) ion with glycine, alanine, and phenylalanine. The thermodynamic functions ΔH°, ΔF°, and Δs° were calculated from the above constants. A form of the Gibbs-Helmholtz equation, d ln K/d(l/T) = -ΔH°/R , was used for calculating ΔH° from the cariation of the equilibrium constants with temperature. ΔH° was calculated from the slope of a straight line fit for the plot log K versus 1/T. The ΔH° so calculated was compared with ΔH° determined from calorimeter measurements. The difference between the values varied from about 0.1 kilocalorie to 2 kilocalories, or about 1 to 20%. Since the heat of the reaction is measured directly in the calorimeter, the calorimetric method should give the better value. it was concluded, therefore, that the variation of euilibrium constants with temperature may not be a reliable method for determining the standard enthalpy change. The reliability of the method probably depends upon the number of points taken and the amount of variation of constants with temperature. It was further concluded that log K does not, in general, vary in an exact linear manner with 1/T. A linear relationship implies that ΔH° is constant with temperature change. All but one of the calorimetric results show a substantial ΔH° change with temperature.