Cyclic block copolypeptoids : synthesis, self-assembly and macroscopic properties

This dissertation presents the first experimental efforts for synthesizing a new class of peptidomimetic polymers, cyclic block copolypeptoids, studying their self-assembly in dilute solution, and examining their macroscopic properties. Cyclic poly(N-methyl-glycine)-b-poly(N-decyl-glycine) (PNMG-b-PNDG) diblock copolymers were synthesized via sequential, N-heterocyclic carbene (NHC)-mediated ring-opening polymerization of NCA monomers with controlled chain length and compositions. Cryo-TEM shows that PNMG105-b-PNDG10 copolymers in methanol (1 mg/mL) form spherical micelles that organize to form cylindrical micelles over time. The formation of cylindrical micelles is attributed to the crystallization of PNDG chains, as revealed by SAED and microDSC analyses. Cyclic PNMG100-b-PNDG10 copolymers form thermo-reversible, free-standing gels at a concentration of 5 wt %. Rheological measurements of the gels reveal that cyclic copolymers produce harder gels than their linear counterparts. Variable-temperature 1H NMR suggests that thermo-reversible gelation is related to any transitions of morphologies formed from the copolymers upon heating and cooling. Analyses by WAXS and SAXS suggest that the cyclic copolymers favor to form cylindrical micelles more than the linear copolymers, leading to formation of harder gels due to more transient networking among the cylindrical micelles. The second part focuses on the synthesis of cyclic triblock terpolypeptoids and their self-assembly in solution. Cyclic poly(N-methyl-glycine)-b-poly(N-allyl-glycine)-b-poly(N-benzyl-glycine) triblock terpolypeptoids were synthesized via sequential addition of monomers. Studies by SEC and NMR suggest block copolymer compositions can be controlled by varying molar ratios of each monomer to NHC. Similarly, cyclic [poly(N-ethyl-glycine)-ran-poly(N-butyl-glycine)]-b-poly(N-methyl-glycine)-b-poly(N-decyl-glycine) triblock terpolypeptoids were synthesized. Analysis by DLS suggests that this terpolymer forms micelles with broad size distributions below the cloud point temperature (Tcp) of PNEG-ran-PNBG blocks, and it may form well-defined, larger micellar aggregates above the Tcp. The third part presents systematic studies of the melting and crystallization of cyclic or linear polypeptoids with various n-alkyl side groups. Studies by DSC show that polypeptoids with butyl or longer side groups have two endothermic melting transitions (Tm,1 \u3c Tm,2). Tm,1 increases and Tm,2 decreases, as the length of n-alkyl side groups increases. Studies by WAXS show that polypeptoids with butyl or longer side groups are well ordered. Tm,1 is attributed to side chain packing and Tm,2 to main polypeptoid packing

Controlling the Dispersion of Nanoparticles in Polymer Matrices

The dispersion of nanoparticles in a polymer matrix is a critical parameter to design and realize targeted morphologies and properties of a final polymer-based nanocomposite. This thesis presents experimental studies to investigate the dispersion of nanoparticles is polymer matrices using specific intermolecular hydrogen bonding between the nanoparticles and polymer matrices under two main topics. The first topic is the impact of sample preparation processes on the properties of polymer carbon nanotube nanocomposites. Polymer nanocomposites composed of poly(styrene-co-vinyl phenol) (PSVPh) copolymers and 5 wt % multi-walled carbon nanotubes (MWNTs) were prepared from three different methods, including melt-mixing and solution casting. The MWNTs were either oxidized to incorporate oxygenated defects or utilized as received. The mechanical properties of the nanocomposites were measured by DMA, and the extent of intermolecular hydrogen bonding between MWNTs and PSVPh was quantified by IR. Our DMA results suggest that melt-mixing leads to more stable morphologies of the final nanocomposites than solution casting does. Additionally, the IR analysis of the nanocomposites indicates melt-mixing can result in the formation of more intermolecular hydrogen bonding between the MWNTs and PSVPh than solution casting, and thus suggests that melt-mixing leads to more reproducible mechanical properties than solution casting. Our DMA and IR results may provide guidelines to realize the desired morphologies and to improve the properties of polymer carbon nanotube nanocomposites by optimizing intermolecular interactions between MWNTs and polymers. The other topic examined seeks to synthesize the starting materials to sequester surface-modified gold nanoparticles in a diblock copolymer matrix. The long term goal of this project is to investigate the impact of enthalpic attractions between the gold nanoparticles and one phase of the diblock copolymer on the nanocomposite morphologies. That is, this system is designed such that the hydroxyl groups on the gold nanoparticles can hydrogen bond with poly(2-vinyl pyridine) blocks of poly(styrene-b-2vinyl pyridine) diblock copolymers. Polystyrene-coated gold nanoparticles were synthesized using thiol-terminated polystyrene (PS-SH) as a stabilizing ligand. The low molecular weight PS-Sh was obtained by the thiolation of bromine-terminated polystyrene (PS-Br), which was synthesized by ATRP. TEM images of the gold nanoparticles shows that the size of the gold nanoparticles can be controlled using this PS-SH as a stabilizing ligand. Additionally, the synthesis of thiol-terminated poly(styrene-co-vinyl phenol) (PSVPh-SH) copolymers was attempted starting with bromine-terminated poly(styrene-co-4-tert-butoxystyrene) copolymers, followed by thiolation and hydrolysis. Our NMR results indicate that the conversion of the bromine-end groups of the copolymers to thiol-end groups by thiolation was complete. However, the conversion of the tert-butoxy groups of the thiolated copolymers to hydroxyl groups by hydrolysis using HCI was not successful. Furthermore, NMR data suggests that this hydrolysis may impact the thiol-end groups of the thiol-terminated copolymers. Our NMR results may provide guidelines such that carefully controlled reaction time and/or HCl amount would improve the success of the PSVPh-Sh synthesis

Networks of intergenic long-range enhancers and snpRNAs drive castration-resistant phenotype of prostate cancer and contribute to pathogenesis of multiple common human disorders

Biological and mechanistic relevance of intergenic disease-associated genetic loci (IDAGL) containing highly statistically significant disease-linked SNPs remains unknown. Here we present the experimental and clinical evidence revealing important role of IDAGL in human diseases. Targeted RT-PCR screen coupled with sequencing of purified PCR products detects widespread transcription at multiple intergenic disease-associated genomic loci (IDAGL) and identifies 96 small non-coding trans-regulatory RNAs of ~ 100-300 nt in length containing SNPs associated with 21 common human disorders (snpRNAs). Functionality of snpRNAs is supported by multiple independent lines of experimental evidence demonstrating their cell-type-specific expression and evolutionary conservation of sequences, genomic coordinates, and biological effects. Analysis of chromatin state signatures, expression profiling experiments using microarray and Q-PCR technologies, and luciferase reporter assays indicate that many IDAGL are Polycomb-regulated long-range enhancers. Expression of snpRNAs in human and mouse cells markedly affects cellular behavior and induces allele-specific clinically-relevant phenotypic changes: NLRP1-locus snpRNAs exert regulatory effects on monocyte/macrophage trans-differentiation, induce prostate cancer (PC) susceptibility snpRNAs, and transform low-malignancy hormone-dependent human PC cells into highly malignant androgen-independent PC. Q-PCR analysis and luciferase reporter assays demonstrate that snpRNA sequences represent allele-specific “decoy” targets of microRNAs which function as SNP-allele-specific modifiers of microRNA expression and activity. We demonstrate that trans-acting RNA molecules facilitating androgen depletion-independent growth (ADIG) in vitro and castration-resistant (CR) phenotype in vivo of PC contain intergenic 8q24-locus SNP variants which were recently linked with increased risk of developing PC. Expression level of 8q24-locus PC susceptibility snpRNAs is regulated by NLRP1-locus snpRNAs, which are transcribed from the intergenic long-range enhancer sequence located in 17p13 region at ~ 30 kb distance from the NLRP1 gene. Q-PCR analysis of clinical PC samples reveals markedly increased snpRNA expression levels in tumor tissues compared to the adjacent normal prostate [122-fold and 45-fold in Gleason 7 tumors (p = 0.03); 370-fold and 127-fold in Gleason 8 tumors (p = 0.0001); for NLRP1-locus and 8q24-locus SnpRNAs, respectively]. Highly concordant expression profiles of the NLRP1-locus snpRNAs and 8q24 CR-locus snpRNAs (r = 0.896; p < 0.0001) in clinical PC samples and experimental evidence of trans-regulatory effects of NLRP1-locus snpRNAs on expression of 8q24-locus SnpRNAs indicate that ADIG and CR phenotype of human PC cells can be triggered by RNA molecules transcribed from the NLRP1-locus intergenic enhancer and down-stream activation of the 8q24-locus snpRNAs. Our results define the intergenic NLRP1 and 8q24 regions as regulatory loci of ADIG and CR phenotype of human PC, reveal previously unknown molecular links between the innate immunity/inflammasome system and development of hormone-independent PC, and identify novel diagnostic and therapeutic targets exploration of which should be highly beneficial for clinical management of PC

Limits of Binaries That Can Be Characterized by Gravitational Microlensing

Due to the high efficiency of planet detections, current microlensing planet searches focus on high-magnification events. High-magnification events are sensitive to remote binary companions as well and thus a sample of wide-separation binaries are expected to be collected as a byproduct. In this paper, we show that characterizing binaries for a portion of this sample will be difficult due to the degeneracy of the binary-lensing parameters. This degeneracy arises because the perturbation induced by the binary companion is well approximated by the Chang-Refsdal lensing for binaries with separations greater than a certain limit. For binaries composed of equal mass lenses, we find that the lens binarity can be noticed up to the separations of $\sim 60$ times of the Einstein radius corresponding to the mass of each lens. Among these binaries, however, we find that the lensing parameters can be determined only for a portion of binaries with separations less than $\sim 20$ times of the Einstein radius.Comment: 5 pages, 3 figures, 1 tabl

Implicit Inverse Force Identification Method of Acoustic Liquid-structure Interaction Finite Element Model

The two-field vibroacoustic finite-element (FE) model requires a relatively large number of degrees of freedom compared to the monophysics model, and the conventional force identification method for structural vibration can be adjusted for multiphysics problems. In this study, an effective inverse force identification method for an FE vibroacoustic interaction model of an interior fluid-structure system was proposed. The method consists of: (1) implicit inverse force identification based on the Newmark-$\beta$ time integration algorithm for stability and efficiency, (2) second-order ordinary differential formulation by avoiding the state-space form causing large degrees of freedom, (3) projection-based multiphysics reduced-order modeling for further reduction of degrees of freedom, and (4) Tikhonov regularization to alleviate the measurement noise. The proposed method can accurately identify the unmeasured applied forces on the in situ application and concurrently reconstruct the response fields. The accuracy, stability, and computational efficiency of the proposed method were evaluated using numerical models and an experimental testbed. A comparative study with the augmented Kalman filter method was performed to evaluate its relative performance.Comment: 31 Pages, 20 Figures, 5 Table

Tau functions as Widom constants

We define a tau function for a generic Riemann-Hilbert problem posed on a union of non-intersecting smooth closed curves with jump matrices analytic in their neighborhood. The tau function depends on parameters of the jumps and is expressed as the Fredholm determinant of an integral operator with block integrable kernel constructed in terms of elementary parametrices. Its logarithmic derivatives with respect to parameters are given by contour integrals involving these parametrices and the solution of the Riemann-Hilbert problem. In the case of one circle, the tau function coincides with Widom's determinant arising in the asymptotics of block Toeplitz matrices. Our construction gives the Jimbo-Miwa-Ueno tau function for Riemann-Hilbert problems of isomonodromic origin (Painlev\'e VI, V, III, Garnier system, etc) and the Sato-Segal-Wilson tau function for integrable hierarchies such as Gelfand-Dickey and Drinfeld-Sokolov.Comment: 26 pages, 6 figure

Fabrication and Evaluation of Mechanical Properties of CF/GNP Composites

AbstractCNT/CFRP (Carbon Nanotube/ Carbon Fiber Reinforced Plastic) composites and GNP/CFRP (Graphene Nano platelet/ Carbon Fiber Reinforced Plastic) have several excellent mechanical properties including, high strength, young's modulus, thermal conductivity, corrosion resistance, electronic shielding and so on. In this study, CNT/CFRP composites were manufactured by varying the CNT weight ratio as 2wt% and 3wt%, While GNP/CFRP composites were manufactured by varying the GNP weight ratio as 0.5wt% and 1wt%. The composites ware manufactured by mechanical method (3-roll-mill). Tensile, impact and wear tests were performed according to ASTM standards D638, D256 and D3181 respectively. It was observed that, increasing the CNT weight ratio improves the mechanical properties, e.g., tensile strength, impact and wear resistance

Effects of Distilled Cervi Pantotrichum Cornu and Rehmannia glutinosa Pharmacopuncture at GB21 (Jianjing) on Heart Rate Variability: A Randomized and Double-blind Clinical Trial

AbstractBackground/PurposeThe purpose of this study was to use heart rate variability (HRV) to investigate the effects of distilled Cervi Pantotrichum Cornu pharmacopuncture and Rehmannia glutinosa pharmacopuncture on the autonomic nervous system.Materials and methodsForty healthy male participants were divided into two groups: the participants of the C-group received distilled Cervi Pantotrichum Cornu pharmacopuncture and those of the R-group received Rehmannia glutinosa pharmacopuncture. The study design was a randomized, double-blind clinical trial. Each participant received one of the two solutions injected at GB21 (Jianjing). The changes in HRV were measured seven times using the QECG-3: LXC3203 system (LAXTHA Inc. Korea). Time-dependent changes in HRV for each group were analyzed using the paired t test (significance level: p < 0.05), and the difference in the HRV fluctuations between the two experimental groups was evaluated using the independent sample test (significance level: p < 0.05).Results and conclusionThe results showed that Cervi Pantotrichum Cornu pharmacopuncture and Rehmannia glutinosa pharmacopuncture tended to activate the autonomic nervous system within the normal range. Cervi Pantotrichum Cornu pharmacopuncture tended to activate the sympathetic nervous system, whereas Rehmannia glutinosa pharmacopuncture tended to activate both the sympathetic and parasympathetic nervous systems