The ability of artificial microswimmers to respond to external stimuli and the mechanistical details of their origins belong to the most disputed challenges in interdisciplinary science. Therein, the creation of chemical gradients is technically challenging, because they quickly level out due to diffusion. Inspired by pivotal stopped flow experiments in chemical kinetics, we show that microfluidics gradient generation combined with a pressure feedback loop for precisely controlling the stop of the flows, can enable us to study mechanistical details of chemotaxis of artificial Janus micromotors, based on a catalytic reaction. We find that these copper Janus particles display a chemotactic motion along the concentration gradient in both, positive and negative direction and we demonstrate the mechanical reaction of the particles to unbalanced drag forces, explaining this behaviour.

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Thesis advisor: Larry W. McLaughlin / The ability to control gene expression has traditionally been pursued at the protein level, using drugs designed to mimic a natural substrate or to disrupt a protein's active site. Traditional drug targeting by competitive and non-competitive inhibitors, however, requires a fairly detailed knowledge of the target protein's three-dimensional structure. More recently, focus has broadened to include alternative methods of genetic control, including the use of single-stranded DNA or RNA probe sequences which control gene expression by targeting the genes themselves. Within the last two decades, peptide nucleic acids (PNAs) – DNA mimics possessing natural bases linked to an N-(2-aminoethyl)-glycine (AEG) backbone – have proven as effective in gene-targeting as traditional synthetic DNA or RNA with the added advantages of tighter binding and greater specificity. Additionally, PNAs are not easily recognized by nucleases, proteases, and peptidases giving them greater resistance to enzyme degradation and making them even more favorable for gene targeting in vivo. Traditional PNA triplexes are composed of two polypyrmidine PNA strands bound to the Watson-Crick and Hoogsteen faces, respectively, of the polypurine strand of target DNA after displacing the polypyrimidine strand of the original DNA duplex. Janus Wedge (JW) residues, on the other hand, utilize unnatural bases linked to the AEG backbone, which are capable of hydrogen bonding to the Watson-Crick faces of both strands of a target DNA duplex. JW triplex formation, then, has a DNA2-PNA stoichiometry, and no Hoogsteen face interactions. The generalization of the DNA duplex targeting strategy by peptide oligomers requires substantial discoveries in the field of PNA research, including an understanding of the three-dimensional structure and folding pattern of these triple-stranded molecules. This report details the crystallization efforts on JW DNA-peptide-DNA triplexes using 11dC811-11T811 target sequences – with and without single base overhangs – and synthetic W8K peptide. Hanging drop vapor diffusion methods showed that while crystal formation was extremely elusive, in narrowing the optimal buffer conditions, 25% PEG concentration was consistently correlated with the most promising crystallization efforts for both the overhanged and non-overhanged sequences. / Thesis (BS) — Boston College, 2005. / Submitted to: Boston College. College of Arts and Sciences. / Discipline: Chemistry. / Discipline: College Honors Program.

Prolactin (PRL) and its receptor (PRLr) have been implicated in the development and progression of human breast cancer. PRL activates its receptor and induces activation of proximal Janus kinase 2 (Jak2) for signal transduction. Here, we sought to determine the role of PRLr-associated peptidyl-prolyl isomerase, cyclophilin A (CypA), in modulating structure/function relationships of the PRLr. It was demonstrated that CypA mediated PRL-induced conformational change of the CFP- and -YFP tagged forms of the PRLr cytoplasmic-tail, whereas CypA inhibition by NIM811 (N-methyl-4-isoleucine cyclosporin) or knockdown blocked the conformational change of the PRLr assessed by Fluorescence Resonance Energy Transfer (FRET) signal or efficiency. To further investigate the consequences of CypA inhibition or knockdown on the PRLr/Jak2 complex mediated signaling/functions, analyses of phospho-tyrosine residues that are believed to be important for interactions/signaling were investigated. It was found that NIM811 inhibition or CypA shRNA knockdown significantly reduced prolactin-stimulated phosphorylation of PRLr/Jak2 intermediates and their association with the PRLr in breast cancer cells. A microarray analysis revealed that NIM811 inhibited approximately 66% of the top 50 PRL-induced genes. NIM811 inhibited breast cancer cell proliferation, survival, migration and anchorage-independent growth. Subsequent NIM811 treatment of a triple negative breast cancer xenograft inhibited primary tumor growth, outgrowth of macro-metastasis and induced central tumor necrosis. Furthermore, loss of CypA in the MMTV-PyMT mouse model demonstrated inhibition of tumorigenesis with significant reduction in lung and lymph node metastasis. Overall, CypA modulates PRL-induced conformational change of the C-terminus of the PRLr through its isomerase activity, altering PRLr/Jak2 complex signaling/functions in breast/mammary tumorigenesis and metastasis.

This Ph.D. thesis reports the discovery and study of several morphologies of ABC triblock copolymer assemblies in block selective solvents. One block copolymer self-assembled into helices (mostly double and some triple helices), and the other block copolymer formed a mixture of structures resembling hamburgers and striped cylinders. The helices, biomimmetic structures which are unusual from block copolymer self assembly, were prepared from the triblock copolymer poly(n-butyl methacrylate)-block-poly(2-cinnamoyloxyethyl methacrylate)-block-poly(tert-butyl acrylate) (PBMA-b-PCEMA-b-PtBA). They were formed spontaneously in several binary solvent mixtures including dichloromethane/methanol, tetrahydrofuran (THF)/methanol, and chloroform/methanol. They were formed in the composition ranges where the mixtures were good for the PtBA block, poor for the PCEMA block, and marginal for the PBMA block. The structure was studied and established by TEM, AFM, DLS and 1H NMR and by TEM tomography. The mechanism and kinetics of helix formation was examined. The Hamburger and striped cylinder structures were produced from poly(tert-butyl acrylate)-block-poly(2-cinnamoyloxyethyl methacrylate)-block-poly(succinated glyceryl monomethacrylate) or (PtBA-b-PCEMA-b-PSGMA) in mixtures of THF, (-)-sparteine and 1- or 2-propanol. Here THF solubilized all the blocks of the copolymer, while propanol was a precipitant for the middle block (PCEMA), and the chiral amine, (-)-sparteine, complexed with PSGMA and made it insoluble. Within the Hamburger-like structure, the “filling” was made of the complexed PSGMA chains and the "buns" were made of PCEMA. The striped cylinders were made of stacking alternating PCEMA and PtBA stubs. The PtBA chains were located on the outer surfaces of both of these structures. With the hamburger structures, after PCEMA crosslinking, we were able to remove the chiral amine by dialysis and make the PSGMA chains soluble again in solvents such as N, N dimethylformamide. The hamburgers were thus separated into two halves, with each half existing as a Janus particle, which had PtBA chains on one side and PSGMA chains on the other side. The Janus particles might have interesting applications, such as in Pickering emulsion stabilization. / Thesis (Ph.D, Chemistry) -- Queen's University, 2010-04-30 18:01:06.281

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Beams are ubiquitous in our everyday life and can be found in a variety of length scales, from large supports of buildings to carbon nanotubes. Similarly, bubbles can also span a variety of scales, ranging from tiny bubbles in a glass filled with champagne to the giant soap bubbles formed by artists to attract crowds. Yet, the behavior of beams and bubbles can often occur so fast that the dynamics go unnoticed. This dissertation aims to understand the mechanics of beams and bubbles in four different examples. We combine table-top experiments with mathematical models to predict how each system will behave when exposed to different extreme conditions. We start by examining the retraction of a rubber band once it has been stretched and released. This process is similar to plucking a string, where the dynamics are governed by tensile and inertial forces, resulting in a trapezoidal shape during retraction. However when a rubber band is stretched and released, a region of high-curvature develops. Our experiments and mathematical model highlight that bending forces can be significant and give rise to a curved self-similar shape to the retracting rubber band. The next example involves the competition of surface tension and twisting on a flexible rod. Most studies in the field of elasto-capillarity have focused on how surface tension can bend an elastic structure, leaving the possibility of twisting unexplored. Here we utilize particles with discrete wettabilities -- or Janus particles -- at liquid interfaces that can be used to twist a flexible cylinder. The third system is focused around the spreading behavior of bubbles on submerged surfaces coated with a layer of oil. These liquid-infused surfaces have remarkable applications due to their ability to minimize contact line pinning. However, this property has mostly been exploited using liquid drops. We here study the early spreading behavior of a bubble once it has made contact with the liquid-infused surface. The final chapter is centered around the collapse of bubbles resting on the surface of an ultra viscous liquid. When a bubble on such a surface is ruptured, the bubble film collapses vertically downwards, leading scientists to believe that gravity is driving the collapse. Yet, interfacial forces are dominant in highly curved liquid surfaces and exceed gravitational forces. By turning the setup upside-down, we show that surface tension is indeed responsible for the collapse and the subsequent wrinkling instability that develops.

The surface and interface of the metal nanoclusters and semiconducting nanomaterials play a key role in determining the electronic structure and overall photophysical properties. A single strand DNA stabilizes the metal nanoclusters, but it also influences the structural change, solvation free energy, and photophysical properties. On the other hand, surface and interface states in Pb and Cd chalcogenide nanomaterials affect the phonon mediated hot carrier relaxation. We applied DFT and DFT based non-adiabatic dynamics methods to study the surface and interface?s effects on the photoexcited processes. In the first part, we have studied the Ag nanoclusters' photophysical properties that are affected by the structural isomers, redox potential, nucleobase passivation, and cluster size. Ag nanoclusters are shown alternative reduction potential, which makes nanoclusters of singlet spin multiplicity thermodynamically favorable. Besides, the optically bright transition in the range of 2.5-3.5 eV is shown metal to ligand charge transfer. It is modulated by the s+p+d orbital mixing in the hole and electron states. We also simulate the charge transfer from the photoexcited PbS QD to organic dye (PDI) attached to the QD surface. Depending on the linker group and the dipole moment of neighboring passivating ligands, the PDI-QD conformations are varies. In response to structural change, the total dipole moment is modulated, changing its electronic structure and hence the photoexcited electron transfer rate from the PbS QD to PDI. We also investigate the inorganic-inorganic interactions in the PbCl2 bridged PbSe NPL and PbSe|CdSe Janus heterostructure. The energy dissipation rate of hot electrons is slower in NPL than the hot hole, while hot e-h relaxed to the band-edge by ?1.0ps in the QD. The slower relaxation rate is rationalized by a large average intraband energy difference and smaller coupling term. Besides, the hot carriers in the NPL are spatially separated by ?1.00 ps, which is a favorable condition for the carrier multiplication process. In Janus QD, (100) interfacial layer creates a structural mismatch in the CdSe part. Besides, the energy offset between the valance localized on PbSe and CdSe part is minimum in the PbSe Janus QD of an interface of (111) facet.