Diffusing Colloidal Probes of Biospecific Interactions and Biological Interfaces

Weak, biospecific and non-specific macromolecular interactions play a major role in fundamental biological process such as cell adhesion, motility, and signaling and in medicine, macromolecules have been integrated into materials for drug delivery and tissue engineering applications. Direct measurements capable of sensitively detecting weak, specific and non-specific macromolecular interactions at interfaces are needed to better understand their function in biological systems and utility in biomaterials. In this dissertation, diffusing colloidal probe microscopy (DCPM) was used to make direct, quantitative measurements of colloidal interactions mediated by weak, specific protein-carbohydrate interactions and interactions with the surface of live cells mediated by specific and non-specific macromolecular interactions. In addition, models were developed capable of predicting colloid and surface interactions mediated by specific biomolecular interactions with direct input of binding affinities for further characterization of experimental results. To study reversible protein-carbohydrate interactions, biospecific adsorption of the sugar-binding protein, Concanavalin A (ConA), to dextran-modified colloidal particles was visualized using fluorescent confocal microscopy and colloidal association dynamics mediated by ConA-dextran interactions were quantified using optical video microscopy. These results demonstrate how aggregation kinetics in colloidal dispersions can be reversibly tuned with competitive ConA-glucose interactions. Direct connections were established between the observed aggregation kinetics and net particle-particle interactions as a function of ConA and glucose concentration. To model this system, Monte Carlo simulations were developed to model bulk and interfacial biomacromolecular binding. With direct input of dissociation constants, particle-particle interactions were predicted for a range of binding affinities and protein concentrations. Dark field video microscopy was used to study interactions between live cells and colloidal particles functionalized with natural and synthetic macromolecules all with relevance to bioengineering. With combined real-time particle tracking and cell boundary determination, particle trajectories can be monitored in relation to their distance from cell surfaces. Particle-cell surface binding lifetimes and potentials of mean force were measured for colloids functionalized with polyethylene glycol (PEG), bovine serum albumin (BSA), dextran, and hyaluronic acid (HA). With the modeling tools developed for colloidal interactions mediated by biospecific binding, the interactions of targeted drug delivery nanoparticles with cell surfaces were characterized for target membrane proteins with varying binding affinities and expression levels. The findings from this work provide a basis for in-depth characterization of biomolecular interactions and biophysical properties of cell surfaces with a combination of experimental and modeling techniques

Building Volunteer Engagement in the Tennessee Extension Master Gardener Program from the Ground Up

This study was designed to assess key volunteer attitudes and perceptions about local and state Extension Master Gardener (EMG) volunteer programs. EMG volunteers in Tennessee completed a total of 759 surveys between January 22 and March 10, 2020. Survey responses showed there was a strong positive perception of local EMG groups and the connection with the University of Tennessee system overall. When respondents were segmented, answers to key questions showed illuminating differences between volunteers with positive and neutral or negative views of the program. The variations in answers show areas of potential emphasis to support healthy local group culture and broader efficacy of the EMG program

Systematic investigation of changes in oxidized cerebral cytochrome c oxidase concentration during frontal lobe activation in healthy adults

Using transcranial near-infrared spectroscopy (NIRS) to measure changes in the redox state of cerebral cytochrome c oxidase (Δ[oxCCO]) during functional activation in healthy adults is hampered by instrumentation and algorithm issues. This study reports the Δ[oxCCO] response measured in such a setting and investigates possible confounders of this measurement. Continuous frontal lobe NIRS measurements were collected from 11 healthy volunteers during a 6-minute anagram-solving task, using a hybrid optical spectrometer (pHOS) that combines multi-distance frequency and broadband components. Only data sets showing a hemodynamic response consistent with functional activation were interrogated for a Δ[oxCCO] response. Simultaneous systemic monitoring data were also available. Possible influences on the Δ[oxCCO] response were systematically investigated and there was no effect of: 1) wavelength range chosen for fitting the measured attenuation spectra; 2) constant or measured, with the pHOS in real-time, differential pathlength factor; 3) systemic hemodynamic changes during functional activation; 4) changes in optical scattering during functional activation. The Δ[oxCCO] response measured in the presence of functional activation was heterogeneous, with the majority of subjects showing significant increase in oxidation, but others having a decrease. We conclude that the heterogeneity in the Δ[oxCCO] response is physiological and not induced by confounding factors in the measurements. © 2012 Optical Society of America

Performance of A1C for the Classification and Prediction of Diabetes

OBJECTIVE Although A1C is now recommended to diagnose diabetes, its test performance for diagnosis and prognosis is uncertain. Our objective was to assess the test performance of A1C against single and repeat glucose measurements for diagnosis of prevalent diabetes and for prediction of incident diabetes. RESEARCH DESIGN AND METHODS We conducted population-based analyses of 12,485 participants in the Atherosclerosis Risk in Communities (ARIC) study and a subpopulation of 691 participants in the Third National Health and Nutrition Examination Survey (NHANES III) with repeat test results. RESULTS Against a single fasting glucose ≥126 mg/dl, the sensitivity and specificity of A1C ≥6.5% for detection of prevalent diabetes were 47 and 98%, respectively (area under the curve 0.892). Against repeated fasting glucose (3 years apart) ≥126 mg/dl, sensitivity improved to 67% and specificity remained high (97%) (AUC 0.936). Similar results were obtained in NHANES III against repeated fasting glucose 2 weeks apart. The accuracy of A1C was consistent across age, BMI, and race groups. For individuals with fasting glucose ≥126 mg/dl and A1C ≥6.5% at baseline, the 10-year risk of diagnosed diabetes was 88% compared with 55% among those individuals with fasting glucose ≥126 mg/dl and A1C 5.7–<6.5%. CONCLUSIONS A1C performs well as a diagnostic tool when diabetes definitions that most closely resemble those used in clinical practice are used as the “gold standard.” The high risk of diabetes among individuals with both elevated fasting glucose and A1C suggests a dual role for fasting glucose and A1C for prediction of diabetes. Although A1C is now recommended for the diagnosis of diabetes (1,2), its precise test performance is uncertain. The lack of a single, clear “gold standard” poses a challenge for determining the performance of A1C. Previous diagnostic studies of A1C have relied exclusively on a single elevated fasting or 2-h glucose values as gold standards (3–5). However, because glucose determinations are inherently more variable than A1C (6), these convenient gold standards are likely to reduce the apparent accuracy of A1C as a diagnostic test. A stronger gold standard would rely on repeated glucose determinations on different days (2), i.e., the recommended approach to diagnosis of diabetes in clinical practice. Alternatively, A1C and fasting glucose can be compared head-to-head against the subsequent development of clinically diagnosed diabetes as the gold standard. We hypothesized that 1) A1C would perform well as a diagnostic and prognostic test for diabetes across its full range and at the American Diabetes Association–recommended threshold of 6.5% and 2) that its performance would be best when judged against stronger, most clinically relevant gold standards

Hubble Space Telescope survey of the Perseus Cluster -IV: Compact stellar systems in the Perseus Cluster core and Ultra Compact Dwarf formation in star forming filaments

We present the results of the first search for Ultra Compact Dwarfs (UCDs) in the Perseus Cluster core, including the region of the cluster around the unusual Brightest Cluster Galaxy (BCG) NGC 1275. Utilising Hubble Space Telescope Advanced Camera for Surveys imaging, we identify a sample of 84 UCD candidates with half-light radii 10 pc < r_e < 57 pc out to a distance of 250 kpc from the cluster centre, covering a total survey area of ~70 armin^2. All UCDs in Perseus lie in the same size-luminosity locus seen for confirmed UCDs in other regions of the local Universe. The majority of UCDs are brighter than M_R = -10.5, and lie on an extrapolation of the red sequence followed by the Perseus Cluster dwarf elliptical population to fainter magnitudes. However, three UCD candidates in the vicinity of NGC 1275 are very blue, with colours (B-R)_0 < 0.6 implying a cessation of star formation within the past 100 Myr. Furthermore, large blue star clusters embedded in the star forming filaments are highly indicative that both proto-globular clusters (GCs) and proto-UCDs are actively forming at the present day in Perseus. We therefore suggest star forming filaments as a formation site for some UCDs, with searches necessary in other low redshift analogues of NGC 1275 necessary to test this hypothesis. We also suggest that tidal disruption of dwarf galaxies is another formation channel for UCD formation in the core of Perseus as tidal disruption is ongoing in this region as evidenced by shells around NGC 1275. Finally, UCDs may simply be massive GCs based on strong similarities in the colour trends of the two populations.Comment: 18 pages, 20 figures, 3 tables. Accepted for publication in MNRA

A Multilevel Model for Comorbid Outcomes: Obesity and Diabetes in the US

Multilevel models are overwhelmingly applied to single health outcomes, but when two or more health conditions are closely related, it is important that contextual variation in their joint prevalence (e.g., variations over different geographic settings) is considered. A multinomial multilevel logit regression approach for analysing joint prevalence is proposed here that includes subject level risk factors (e.g., age, race, education) while also taking account of geographic context. Data from a US population health survey (the 2007 Behavioral Risk Factor Surveillance System or BRFSS) are used to illustrate the method, with a six category multinomial outcome defined by diabetic status and weight category (obese, overweight, normal). The influence of geographic context is partly represented by known geographic variables (e.g., county poverty), and partly by a model for latent area influences. In particular, a shared latent variable (common factor) approach is proposed to measure the impact of unobserved area influences on joint weight and diabetes status, with the latent variable being spatially structured to reflect geographic clustering in risk

A survey for redshifted molecular and atomic absorption lines I

We are currently undertaking a large survey for redshifted atomic and molecular absorption ... only one clear and one tentative detection were obtained: HI absorption at z = 0.097 in PKS 1555-140 and OH absorption at z =0.126 in PKS 2300-189, respectively... In order to determine why no clear molecular absorption was detected in any of the 13 sources searched, we investigate the properties of the five redshifted systems currently known to exhibit OH absorption. In four of these, molecules were first detected via millimetre-wave transitions and the flat radio spectra indicate compact background continuum sources, which may suggest a high degree of coverage of the background source by the molecular clouds in the absorber. Furthermore, for these systems we find a relationship between the molecular line strength and red optical--near infrared (V-K) colours, thus supporting the notion that the reddening of these sources is due to dust, which provides an environment conducive to the formation of molecules. Upon comparison with the V-K colours of our sample, this relationship suggests that, presuming the reddening occurs at the host galaxy redshift at least in some of the targets, many of our observations still fall short of the sensitivityrequired to detect OH absorption, although a confirmation of the ``detection'' of OH in 2300-189 could contravene this.Comment: 13 pages, loads of figures, accepted by MNRA

Direct Evidence for Termination of Obscured Star Formation by Radiatively Driven Outflows in Reddened QSOs

We present optical to far-infrared photometry of 31 reddened QSOs that show evidence for radiatively driven outflows originating from AGN in their rest-frame UV spectra. We use these data to study the relationships between the AGN-driven outflows, and the AGN and starburst infrared luminosities. We find that FeLoBAL QSOs are invariably IR-luminous, with IR luminosities exceeding 10^{12} Solar luminosities in all cases. The AGN supplies 76% of the total IR emission, on average, but with a range from 20% to 100%. We find no evidence that the absolute luminosity of obscured star formation is affected by the AGN-driven outflows. Conversely, we find an anticorrelation between the strength of AGN-driven outflows, as measured from the range of outflow velocities over which absorption exceeds a minimal threshold, and the contribution from star formation to the total IR luminosity, with a much higher chance of seeing a starburst contribution in excess of 25% in systems with weak outflows than in systems with strong outflows. Moreover, we find no convincing evidence that this effect is driven by the IR luminosity of the AGN. We conclude that radiatively driven outflows from AGN can have a dramatic, negative impact on luminous star formation in their host galaxies. We find that such outflows act to curtail star formation such that star formation contributes less than ~25% of the total IR luminosity. We also propose that the degree to which termination of star formation takes place is not deducible from the IR luminosity of the AGN.Comment: Accepted for publication in Ap

Gemini/GMOS Imaging of Globular Cluster Systems in Five Early-type Galaxies

This paper presents deep high quality photometry of globular cluster (GC) systems belonging to five early-type galaxies covering a range of mass and environment. Photometric data were obtained with the Gemini North and Gemini South telescopes in the filter passbands g', r', and i'. The combination of these filters with good seeing conditions allows an excellent separation between GC candidates and unresolved field objects. Bimodal GC colour distributions are found in all five galaxies. Most of the GC systems appear bimodal even in the (g' -r') vs (r' -i') plane. A population of resolved/marginally resolved GC and Ultra Compact Dwarf candidates was found in all the galaxies. A search for the so-called "blue tilt" in the colour-magnitude diagrams reveals that NGC 4649 clearly shows that phenomenon although no conclusive evidence was found for the other galaxies in the sample. This "blue tilt" translates into a mass-metallicity relation given by Z \propto M^0.28\pm0.03 . This dependence was found using a new empirical (g' -i') vs [Z/H] relation which relies on an homogeneous sample of GC colours and metallicities. This paper also explores the radial trends in both colour and surface density for the blue (metal-poor) and red (metal-rich) GC subpopulations. As usual, the red GCs show a steeper radial distribution than the blue ones. Evidence of galactocentric colour gradients is found in some of the GC systems, being more significant for the two S0 galaxies in the sample. Red GC subpopulations show similar colours and gradients to the galaxy halo stars in their inner region. A GC mean colour-galaxy luminosity relation, consistent with [Z/H] \propto L_B ^0.26\pm0.08, is present for the red GCs. An estimate of the total GC populations and specific frequency SN values is presented for NGC 3115, NGC 3379, NGC 3923 and NGC 4649.Comment: 23 pages, 13 figures and 9 tables. Tables A1 and A2 will be published in full online only. Accepted for publication in MNRA