The Physicochemical Properties and Cellular Toxicity of Variably Synthesized Zinc Oxide Nanoparticles

Nanotechnology has grown exponentially since its inception in the early 1970’s. Since then, bionanotechnological devices and treatment options have significantly improved disease treatments and patient outcomes; however, this rapid growth in consumer related products has also prompted concern. Zinc oxide nanoparticles (nZnO), known for their inherent toxicity and prevalent global use in consumer products and medical applications, have received much of this attention. Significant research efforts have focused on both toxicity remediation through material property modification and the exploitation of these same factors to create potential cancer therapeutics. There is general agreement that the physicochemical properties of nZnO strongly contribute to NP-induced toxicity; however, inconsistencies in the material property characterization methods employed, and an understanding of how those properties influence cytotoxicity in mammalian cells has led to discrepancies in the literature. Additionally, more research is needed to connect the material properties of nZnO to downstream cellular responses. Here, a panel of variably synthesized nZnO was utilized to thoroughly investigate the material properties of the particles as they relate to cytotoxicity, oxidative stress, and transcriptome changes in different mammalian cell types. The goals of this study are three-fold: i) reduce NP agglomeration and sedimentation tendencies within complex media and achieve dispersion stability, ii) define which material property interactions have the greatest potential to affect cellular toxicity, and to iii) examine the preferential toxicity of nZnO towards Jurkat leukemic cells through genetic expression studies. Chapter 2 highlights the importance of dispersion stability and the effect of fetal bovine serum (FBS) proteins on the dispersion stability, dosimetry and NP-induced cytotoxicity of nZnO in suspension and adherent in vitro cell culture models. The presence of surface adsorbed proteins from the FBS on the nZnO decreased agglomeration and sedimentation potential. Furthermore, FBS-stabilized nZnO dispersions resulted in toxicity increases in suspension cells when compared to unstable dispersions; however, toxicity was decreased in adherent cell models with stable dispersions. These observations indicate that improved dispersion stability leads to increased NP bioavailability for suspension cells and reduced NP sedimentation onto adherent cell layers resulting in more accurate in vitro toxicity assessments. In Chapter 3, we utilized an expanded panel of nZnO synthesized through wet chemical and high temperature methods, followed by thorough characterization to examine the importance of material property changes in NP-induced toxicity. We found our diverse set of nZnO displayed significant differences in surface reactivity, dissolution potential and cytotoxicity towards cancerous and primary T cells. Additionally, principal component analysis (PCA) suggested that the synthesis procedure conferred unique material properties, and can be a determinant of cellular cytotoxicity. Furthermore, we showed that attributing NP-induced toxicity to one specific material property is shortsighted and that complex interactions between these properties needs to be considered. Finally, Chapter 4 introduces future work dedicated to investigating transcriptome changes in cancerous and primary T cells exposed to nZnO. Both cell types demonstrated significant up- and down-regulation of genes in a dose-dependent manner. Many significant differentially expressed genes (SDEGs) corresponded to proteins involved in the sequestration and transport of ionic zinc confirming the importance of nZnO in the cytotoxic response. Additional analysis will focus on the importance of specific SDEGs involved in the regulation of oxidative stress pathways, cellular metabolism, inflammation, T cell activation, and protein misfolding in the NP-induced toxicity mechanism

An uncomplicated method for making periodical identical radiographs of experimental bone lesions in the rat. A technical report.

An uncomplicated method for making periodically similar radiographs of the rat mandible is presented. A stent was produced by making an impression of the rat maxilla using an acrylic resin, incorporating an orthodontic wire: and fixing the impression to a RinnTM holder for the detector of the Sens-A-RayTM direct digital radiographie system This inflexible stent was then inserted and fixed to the maxilla of rats, anaesthetised with HypnormTM(fluanison 10mg/ml and fentanyl 0.2 mg/ml). In this fashion, serial radiographs were taken once a week for 12 weeks, making it possible to follow the healing of experimental bone lesions

Grade expectations: how well can past performance predict future grades?

Students in the UK apply to university with teacher-predicted examination grades, rather than actual results. These predictions have been shown to be inaccurate, and to favour certain groups, leading to concerns about teacher bias. We ask whether it is possible to improve on the accuracy of teachers’ predictions by predicting pupil achievement using prior attainment data and machine learning techniques. While our models do lead to a quantitative improvement on teacher predictions, substantial inaccuracies remain. Our models also underpredict high-achieving state school pupils and low socio-economic status pupils, suggesting they have more volatile education trajectories. This raises questions about the use of predictions in the UK system

Serum Proteins Enhance Dispersion Stability and Influence the Cytotoxicity and Dosimetry of ZnO Nanoparticles in Suspension and Adherent Cancer Cell Models

Agglomeration and sedimentation of nanoparticles (NPs) within biological solutions is a major limitation in their use in many downstream applications. It has been proposed that serum proteins associate with the NP surface to form a protein corona that limits agglomeration and sedimentation. Here, we investigate the effect of fetal bovine serum (FBS) proteins on the dispersion stability, dosimetry, and NP-induced cytotoxicity of cationic zinc oxide nanoparticles (nZnO) synthesized via forced hydrolysis with a core size of 10 nm. Two different in vitro cell culture models, suspension and adherent, were evaluated by comparing a phosphate buffered saline (PBS) nZnO dispersion (nZnO/PBS) and an FBS-stabilized PBS nZnO dispersion (nZnO – FBS/PBS). Surface interactions of FBS on nZnO were analyzed via spectroscopic and optical techniques. Fourier transformed infrared spectroscopy (FTIR) confirmed the adsorption of negatively charged protein components on the cationic nZnO surface through the disappearance of surfaced-adsorbed carboxyl functional groups and the subsequent detection of vibrational modes associated with the protein backbone of FBS-associated proteins. Further confirmation of these interactions was noted in the isoelectric point shift of the nZnO from the characteristic pH of 9.5 to a pH of 6.1.In nZnO – FBS/PBS dispersions, the FBS reduced agglomeration and sedimentation behaviors to impart long-term improvements (\u3e24 h) to the nZnO dispersion stability. Furthermore, mathematical dosimetry models indicate that nZnO – FBS/PBS dispersions had consistent NP deposition patterns over time unlike unstable nZnO/PBS dispersions. In suspension cell models, the stable nZnO – FBS/PBS dispersion resulted in a ~33 % increase in the NP-induced cytotoxicity for both Jurkat leukemic and Hut-78 lymphoma cancer cells. In contrast, the nZnO – FBS/PBS dispersion resulted in 49 and 71 % reductions in the cytotoxicity observed towards the adherent breast (T-47D) and prostate (LNCaP) cancer cell lines, respectively. Presence of FBS in the NP dispersions also increased the reactive oxygen species generation. These observations indicate that the improved dispersion stability leads to increased NP bioavailability for suspension cell models and reduced NP sedimentation onto adherent cell layers resulting in more accurate in vitro toxicity assessments

Stranger Things on TikTok: young people, climate change and upside down political communication

No abstract available

Junior Recital: Catherine Rothery, flute

This recital is presented in partial fulfillment of requirements for the degree Bachelor of Music in Performance. Ms. Rothery studies flute with Christina Smith.https://digitalcommons.kennesaw.edu/musicprograms/1028/thumbnail.jp

Senior Recital: Shelby Jones, bassoon

This recital is presented in partial fulfillment of requirements for the degree Bachelor of Music in Performance. Ms. Jones studies bassoon with Laura Najarian.https://digitalcommons.kennesaw.edu/musicprograms/1130/thumbnail.jp

Influence of Aging on Bioaccumulation and Toxicity of Copper Oxide Nanoparticles and Dissolved Copper in the Sediment-Dwelling Oligochaete <i>Tubifex tubifex</i>:A Long-Term Study Using a Stable Copper Isotope

For engineered metal nanoparticles (NPs), such as copper oxide (CuO) NPs, the sediment is recognized as a major compartment for NP accumulation. Sediment-dwelling organisms, such as the worm Tubifex tubifex, will be at particular risk of metal and metal NP exposure. However, a range of complex transformation processes in the sediment affects NP bioavailability and toxicity as the contamination ages. The objective of this study was to examine bioaccumulation and adverse effects of CuO NPs in T. tubifex compared to dissolved Cu (administered as CuCl2) and the influence of aging of spiked sediment. This was done in a 28-day exposure experiment with T. tubifex incubated in clean sediment or freshly spiked sediment with different concentrations of dissolved Cu (up to 230 μg g−1 dw) or CuO NPs (up to 40 μg g−1 dw). The experiment was repeated with the same sediments after it had been aged for 2 years. To obtain a distinct isotopic signature compared to background Cu, both Cu forms were based on the stable isotope 65Cu (&gt;99%). The 28-day exposure to sediment-associated dissolved 65Cu and 65CuO NPs resulted in a clear concentration-dependent increase in the T. tubifex65Cu body burden. However, despite the elevated 65Cu body burdens in exposed worms, limited adverse effects were observed in either of the two experiments (e.g., above 80% survival in all treatments, low or no effects on the growth rate, feeding rate, and reproduction). Organisms exposed to aged sediments had lower body burdens of 65Cu than those exposed to freshly spiked sediments and we suggest that aging decreases the bioavailability of both 65Cu forms. In this study, the use of a stable isotope made it possible to use environmentally realistic Cu concentrations and, at the same time, differentiate between newly accumulated 65Cu and background Cu in experimental samples despite the high background Cu concentrations in sediment and T. tubifex tissue. Realistic exposure concentrations and aging of NPs should preferably be included in future studies to increase environmental realism to accurately predict the environmental risk of metal NPs

Etude en rayons X cohérents de la dynamique de suspensions concentrées de sphères dures

Les suspensions colloïdales de particules sphériques présentant des interactions de type sphères dures font partie des systèmes les plus simples et les plus largement étudiés en Matière Molle. Elles peuvent être considérées comme systèmes modèles pour tester des théories plus générales, par exemple en ce qui concerne la cristallisation [1] ou la transition vitreuse [2]. Malgré de nombreux résultats théoriques et expérientaux dans ce domaine, le comportement dynamique des suspensions de sphères dures n'a pas été complètement élucidé.La spectroscopie à corrélation de photons X (XPCS) est une technique de diffusion cohérente équivalente à la Diffusion Quasi-Elastique de la Lumière [3], qui est un des principaux outils d'investigation de la dynamique colloïdale [4]. Comparée à la luière visible, l'utilisation de rayons X procure des rensignements sur les transferts de moment de plus haute énergie, et évite les diffusions multiples - phénomène qui complique sensiblement les études en DQEL pour les échantillons concentrés. De plus, l'utilisation du détecteur 2D compteur de photons (MAXIPIX) disponible sur la ligne ID10 (ESRF) donne des renseignements sur l'évolution de la dynamique de l'échantillon au cours de l'exposition, via les fonctions de corrélation à deux temps.Dans ce travail, nous avons étudié une suspension de spheres colloïdales de PMMA (poly(méthylmétacrylate)) stériquement stabilisées. La distribution en taille des particules et leur concentration ont été obtenues par diffusion de rayons X aux petits angles (SAXS). Les expériences de XPCS effectuées aux plus grandes fractions volumiques en particules (>0.5) mettent en évidence à la fois des temps de diffusion courts et des temps longs autour des pics de Bragg. Une comparaison avec une précédente étude [5] montre, pour une petite gamme de fractions volumiques, une modification drastique de la loi d'échelle entre les temps de relaxation courts et les temps longs qui avait été initialement proposée par Segrè et Pusey [6]. L'analyse des fonctions de corrélation à deux temps révèle un comportement dynamique complexe des échantillons légèrement au-dessus de la transition vitreuse, alors qu'on n'observe aucun signe de modifications structurales via diffusion statique. Utiliser la XPCS sur des suspensions en écoulement dans des canaux cylindriques avait fait ses preuves pour renseigner à la fois sur les propriétés dynamiques et d'écoulement de suspensions diluées [7]. Ici, nous discutons les potentialités et les limites de cette méthode, en étudiant l'interaction entre les propriétés rhéologiques et dynamiques dans ces systèmes complexes modèles que sont les verres colloïdaux.[1] P. N. Pusey and W. van Megen. In: Nature 320.6060 (Mar. 1986), pp. 340 342 [2] P. N. Pusey and W. van Megen. In: Phys. Rev. Lett. 59 (18 1987), pp. 2083 2086.[3] V. A. Martinez et al. In: The Journal of Chemical Physics 134.5, 054505 (2011), p. 054505.[4] B. J. Berne and R. Pecora. Dynamic Light Scattering with application to chemistry, biology and physics. Dover Publications, New York, 2000. [5] D. Orsi et al. Dynamics in dense hard-sphere colloidal suspensions . In: Phys. Rev. E 85 (1 2012), p. 011402. doi: 10.1103/PhysRevE.85.011402. url: http://link.aps.org/doi/1 0.1103/PhysRevE.85.011402. [6] P. N. Segrè and P. N. Pusey. In: Phys. Rev. Lett. 77.4 (1996), pp. 771 774.[7] A. Fluerasu et al. In: New Journal of Physics 12.3 (2010)Colloidal suspensions of spherical particles presenting hard-sphere like interactions is one of the simplest and most widely studied systems of soft condensed matter. They can be treated as a model for testing fundamental theories, regarding e.g. crystallization [1] or glass transition [2]. Despite the long history of both theoretical and experimental research, the dynamic behavior of hard sphere suspensions still lacks a complete understanding.X-ray Photon Correlation Spectroscopy (XPCS) is a coherent scattering technique equivalent to Dynamic Light Scattering (DLS) [3], which is one of the main tools used in the study of colloidal dynamics [4]. Comparing to visible light, the use of X-rays provides access to higher momentum transfer vector values and allows to avoid multiple scattering a phenomena significantly complicating DLS measurements on concentrated samples. Moreover, the use of a fast, single photon counting area detector (MAXIPIX) available at the ID10 beamline at ESRF gives insight into the evolution of sample dynamics during the measurement time by the means of two-time correlation functions.In this work suspensions of sterically stabilized poly(methyl methacrylate) (PMMA) colloidal spheres were used. Particle size, polydispersity and volume fractions of the samples were obtained using the Small-Angle X-ray Scattering (SAXS) technique. XPCS measurements at high volume fractions (>0.5) show both short- and long-time diffusive behaviour for scattering vector values around, but not restricted to the structure factor peak position. A comparison with an earlier study [5] shows a dramatic change in the approximate scaling between the short- and long-time relaxation rates, initially proposed by Segrè and Pusey in [6], over a small range of volume fractions. The analysis of two-time correlation functions reveals complex dynamic behaviour of a sample slightly above the glass transition, while no signs of structural changes are observed in the static scattering patterns. The studies indicate the dynamics being governed by a jamming transition driven by restrictions in free volume rather than a glass transition as know from the mode-coupling theory. A combination of XPCS with flow in a cylindrical channel has demonstrated previously to give both dynamic and flow properties of dilute suspensions [7]. Here we discuss the potential and limitations of this method in the study of the interplay between rheological properties and dynamics in complex systems such as colloidal glasses. [1] P. N. Pusey and W. van Megen. In: Nature 320.6060 (Mar. 1986), pp. 340 342[2] P. N. Pusey and W. van Megen. In: Phys. Rev. Lett. 59 (18 1987), pp. 2083 2086.[3] V. A. Martinez et al. In: The Journal of Chemical Physics 134.5, 054505 (2011), p. 054505.[4] B. J. Berne and R. Pecora. Dynamic Light Scattering with application to chemistry, biology and physics. Dover Publications, New York, 2000.[5] D. Orsi et al. Dynamics in dense hard-sphere colloidal suspensions . In: Phys. Rev. E 85 (2012), p. 011402.[6] P. N. Segrè and P. N. Pusey. In: Phys. Rev. Lett. 77.4 (1996), pp. 771 774.[7] A. Fluerasu et al. In: New Journal of Physics 12.3 (2010)SAVOIE-SCD - Bib.électronique (730659901) / SudocGRENOBLE1/INP-Bib.électronique (384210012) / SudocGRENOBLE2/3-Bib.électronique (384219901) / SudocSudocFranceF