994 research outputs found
Amphiphilic block copolymers : synthesis, self-assembly and applications
No full textSelf-assembly of amphiphilic block copolymers in aqueous solution is one of the most important nanotechnological methods to prepare nanocarriers for
different applications, such as drug delivery, biosensor, nanoreactor and so on. Synthesis of new types of amphiphilic block copolymers with novel
functionality and detailed characterization of self-assembly, influenced by self-assembly methods and different other parameters (molecular weight,
hydrophilic to hydrophobic ratio), are important. Especially, building up the relationship between the self-assembled nanomorphologies and molecule
constitution are helpful to understand amphiphilic block copolymer self-assemble theroy.
In this thesis, I present to you the influence of different parameters on the self-assembly nanostructures for the poly(dimethylsiloxane)-
block-poly(2-methyl-2-oxazoline) (PDMS-b-PMOXA) amphiphilic block copolymers.3D phase diagram clearly shows in which domain the PDMS-b-PMOXA
self-assemble into polymersome. The polymersome are possible for us to constribute the nano-sized based nanoreactor.
In addition, in order to develop more functional amphiphilic block copolymers and enlarge the potential application areas, another two types of
copolymers, grafted poly(2-methyl-2-oxazoline)-graft(ss)-poly(e-caprolactone) (PMOXA-graft(ss)-PCL) and linear poly(2-ethyl-2-oxazoline)-block-
poly(e-caprolactone)-ss-poly(L-lysine) (PEtOXA-b-PCL-ss-PLL), were designed and synthesized with reduction responsiveness, utilizing different
polymerization techniques, including ring openning polymerization and "graft-to" technology. Due to the amphiphilicity of these two types of
copolymers, nanoparticles are formed by them in aqueous solution. The primary evaluation of these two new type amphiphilic block copolymers
demonstrated that they can be promising candidates as smart nanocarries for the application of drug delivery.
In this dissertation, the result of our research have been comprehensivly compared with other publications and results from different groups.
We have new findingS. We find one new nano-object with 80-100 nm diameter, but without hollow aqueous cavity.
We also realize that basing on poly(2-ethyl-2-oxazoline)-block-poly(e-caprolactone)-ss-poly(L-lysine) (PEtOXA-b-PCL-ss-PLL) copolymer, it is possible
to synthesize more functional copolymer, for example introducing the pH-cleavable linker between PEtOXA and PCL, to mimic more closely the virus delivery
gene into cells
Functional surfaces through biomimetic block copolymer membranes
No full textFundamental scientific research was always interested by the concept of mimicking Nature because of the presence of remarkable designs. In particular, due to their importance in numerous cellular processes, biological membranes got great interest in biochemical and biophysical research. It is crucial to understand the membrane morphology, the role of individual membrane components, and also to correlate the membrane structure to its various functions. In addition to contributing to fundamental understanding, membranes are also highly attractive for industrial research and technological development. However, the complexity and fragility of natural membranes often limit their direct use. For that reason, the development of membrane models is indispensable. Suitable building blocks for model systems could be lipids or amphiphilic polymers.
The versatility of polymer chemistry allows the fine-tuning of biomimetic membranes in solution and on solid supports. Methacrylate-based amphiphilic triblock copolymers poly (2-hydroxyethyl methacrylate)-b-poly (butyl methacrylate)-b-poly (2-hydroxyethyl methacrylate) PHEMA-b-PBMA-b-PHEMA were designed in solution and on gold surfaces. By varying the hydrophilic to hydrophobic ratio as well as the chain length, the polymers self-assembled into nanoparticles and micelles in solution. The micelles were used to encapsulate and release hydrophobic model payloads, showing their potential use as intracellular drug delivery systems. Also, artificial planar membranes as mimics of natural membranes were synthesized directly from gold surfaces. Upon the variations in thickness and packing density, potential incorporation of membrane proteins was shown at a determined grafting density. Upon insertion of those proteins, this system may find its application as biosensing devices.
In solution, the nanostructures were characterized by using a wide range of methodologies including static and dynamic light scattering, transmission electron microscopy, ThioGlo detection, UV-vis spectroscopy, fluorescence spectroscopy and fluorescence correlation microscopy. On solid supports, atomic force microscopy and surface plasmon resonance along with neutron reflectivity were used to gain insights into morphology, homogeneity, grafting density and thickness of the layers. To demonstrate the planar membranes’ biomimetic potential, they were incubated with different channel proteins: Outer Membrane Protein F, Aquaporin Z and alpha-hemolysin. Occurring interactions were detected by in-situ ATR-FTIR and electrochemical impedance spectroscopy. In summary, this thesis might impact fundamental membrane science as well as prospective biotechnological applications
Protein nanoreactors and native enzymes for controlled/living radical polymerization
No full textThe present PhD thesis entitled ‚Protein Nanoreactors and Native Enzymes for Controlled/Living Radical Polymerization‘ began with the hypothesis that protein-catalyst conjugates are able to beneficially influence controlled/living radical polymerization, i.e. atom transfer radical polymerization (ATRP). The general motivation for this work is driven by problems that occur when transition metal catalyst are used for ATRP. These most commonly used catalyst are only biocompatible to a limited extend and the resulting polymers show unwanted coloration due to the remaining catalyst. Moreover, by conjugating the catalyst into the cavities of a protein cage, we could gain insights into the catalytic mechanism of ATRP as well as into effects of the confined space. Polymer chemistry in particular enables us to perform successful research with proteins since synthetic strategies in a biocompatible environment, i.e. aqueous solution are well established.
Inspired by problems addressed earlier in our research group, we developed a robust conjugation and purification method to attach transition metal catalysts to proteins or enclose them into protein cages using bis-aryl hydrazone linker chemistry. Successively, we determined good performing ATRP conditions that allowed for significant lower catalyst concentrations. Thus, activators regenerated by electron transfer (ARGET) ATRP was used to constantly regenerate the catalyst into its active form by the means of a reducing agent.
We described one of these protein-catalyst conjugates in full detail. The ATRP catalyst was conjugated to the globular protein bovine serum albumin (BSA) and the complex was extensively characterized using biological and physical methods. The resulting conjugate was used to polymerize N-isopropyl acrylamide (NiPAAm) and poly(ethylene glycol) methyl ether acrylate (PEGA) in aqueous solution and was subsequently analyzed upon its structural integrity after polymerization. The ARGET ATRP of NiPAAm and PEGA yielded polymers with a moderate control over the molecular weight and the polydispersity of the polymers. However, our focus was to reduce the residual copper in polymers. Thus, BSA that served as a functional handle was used to remove the copper containing catalyst effectively from solution. We showed a reduction of residual copper to ppb levels, either by precipitation or by Dynabead removal.
Further, our findings showed that some metalloproteins can mediate ATRP. Enzymes have been introduced into synthetic chemistry as green and very selective alternatives to conventional catalysts. In polymer chemistry enzymes have been used as catalysts for polycondensation, ring-opening polymerizations, free radical polymerizations of vinyl-type monomers and the polymerization of aromatic compounds by radical-induced oxidative coupling. However, controlled/living radical polymerizations catalyzed by enzymes have not been exploited. Our results and the ones from di Lena represent the first reports of biocatalytic, controlled/living radical polymerization. Bringing those enzymes into organic solution, e.g. by conjugation of end-group-reactive polymers such as PEG, poly(oxazolines) and amphiphilic blockcopolymers to the surface-exposed lysines or cysteins of the enzymes, could lead to interesting new routes towards environmentally friendly catalysis, functional materials or functional nanosystems.
The group II chaperonin thermosome (THS) from the archaea Thermoplasma acidophilum is reported as protein nanoreactor for ATRP. For that purpose, a copper catalyst was entrapped into the THS. The confined space within the protein nanoreactor favorably influenced the polymerization of NiPAAm and PEGA under ARGET ATRP conditions in comparison to polymerizations carried out with the globular protein BSA. This concept was adapted and instead of the copper-complex, we covalently entrapped an enzyme as ATRP catalyst. We demonstrated that the space constriction in the THS has similar effects on the final polymer product, as shown for THS-LxCu. Protein nanoreactors with encapsulated enzymes, i.e. ATRPases, could help to understand the reaction mechanisms behind ATRPases.
Further, we described a way to render protein cages, i.e. THS, gated nanoreactors. The gated behavior of THS driven by the hydrolysis of ATP and ATP analogues was shown by enzymatic assays. The incorporation of HRP into THS allowed to study the opening and closing of the cage by converting the non-fluorescent dihydro rhodamine 6G into its fluorescent form rhodamine 6G. In addition, nanomechanical sensing with cantilever arrays measured the surface stress induced by the opening and closing of the protein cage in response to ATP analogues. The field of gated nanoreactors is still in its infancy. Thus, gated nanoreactors could be used in the areas of medicine, sensing, synthesis of drugs and other chemical products, and as analytical tools to study reaction mechanisms in confined volumes
Lateral diffusion processes in biomimetic polymer membranes
No full textMolecular self-assembly offers an important bottom-up approach to generate new materials with great potential for applications in nano-, life- and medical- sciences and engineering. The interest in “soft” materials suitable for the generation of artificial, biomimetic membranes has increased rapidly over the last years. These membranes combine the advantages of specificity and efficiency found in nature and the robustness and stability of synthetic materials from polymer science. There are currently two approaches to design biomimetic membranes. One uses natural phospholipids, while the other ones uses synthetic lipid mimics as the advanced alternative, which have shown great mechanical and chemical stability compared to their natural counterparts. This is important for technological application where durable devices are required. Biological membrane proteins, which provide selective and very efficient membrane transport, can be inserted into these synthetic block copolymer membranes. This combination of a synthetic membrane with biological membrane proteins is an intriguing phenomenon because the fundamental requirements for successful insertion are still matter of debate. One important issue is that polymeric membranes have thicknesses that exceed the height of the membrane proteins by several factors and the two lengths actually do not match. However, this significant height mismatch can be overcome by choosing a polymer with high flexibility, which has been shown to allow membrane proteins insertion in their active conformation. Flexibility and fluidity are essential membrane properties allowing successful generation of biomimetic membranes.
In this thesis, the fluid properties of synthetic membranes composed of synthetic amphiphiles are studied based on a large library of block copolymers. These consist of poly(2-methyloxazoline) (PMOXA) and poly(dimethylsiloxane) (PDMS) and are used as diblock (PMOXA-b-PDMS, AB) and triblock (PMOXA-b-PDMS-b-PMOXA, ABA) copolymers. Variation of the molecular weight induces changes in the membrane thickness and thus the fluidity of the membrane. The diffusion of membrane proteins within synthetic triblock copolymer membranes was investigated. The study revealed that the membrane proteins are mobile even at hydrophobic mismatches of up to 7 nm, which is a factor of seven compared to mismatches existing in biological membranes. The advantage of PDMS-containing block copolymers is their enormous flexibility even at high molecular weights, which provides a similar membrane environment compared to biological phospholipid membranes. This explains and displays the ability of PDMS to compress in contact to membrane proteins. Their diffusion decreases steadily with increasing thickness mismatch.
The importance of a very flexible polymer for the generation of biomimetic membranes was elucidated for membrane protein insertion, such as PDMS, which offers high fluidity and high membrane stability within membranes with even large thicknesses. The properties of these synthetic membranes investigated here, i.e. fluidity, lateral diffusion and membrane thickness, are important for the generation of biomimetic membranes for technological applications
Treatment of unruptured intracranial aneurysms : a surgical long-term evaluation for preoperative predictive analytics
No full textAuthor Dr.med.univ. Nico Henrique Stroh-HollyDissertation Johannes Kepler Universität Linz 202
Advanced computational biology methods identify molecular switches for malignancy in an EGF mouse model of liver cancer.
No full textThe molecular causes by which the epidermal growth factor receptor tyrosine kinase induces malignant transformation are largely unknown. To better understand EGFs' transforming capacity whole genome scans were applied to a transgenic mouse model of liver cancer and subjected to advanced methods of computational analysis to construct de novo gene regulatory networks based on a combination of sequence analysis and entrained graph-topological algorithms. Here we identified transcription factors, processes, key nodes and molecules to connect as yet unknown interacting partners at the level of protein-DNA interaction. Many of those could be confirmed by electromobility band shift assay at recognition sites of gene specific promoters and by western blotting of nuclear proteins. A novel cellular regulatory circuitry could therefore be proposed that connects cell cycle regulated genes with components of the EGF signaling pathway. Promoter analysis of differentially expressed genes suggested the majority of regulated transcription factors to display specificity to either the pre-tumor or the tumor state. Subsequent search for signal transduction key nodes upstream of the identified transcription factors and their targets suggested the insulin-like growth factor pathway to render the tumor cells independent of EGF receptor activity. Notably, expression of IGF2 in addition to many components of this pathway was highly upregulated in tumors. Together, we propose a switch in autocrine signaling to foster tumor growth that was initially triggered by EGF and demonstrate the knowledge gain form promoter analysis combined with upstream key node identification
Synthesis and characterization of ultra-small magnetic FeNi/G and NiCo/G nanoparticles
No full text10 páginas, 13 figuras, 1 tabla.-- Trabajo presentado como póster a la 19th International Conference on Magnetism celebrada en Korea del 8 al 13 de julio de 2012.Ultra-small magnetic nanoparticles consisting of NiCo and FeNi alloys enclosed within graphitic shells (NiCo/G and FeNi/G) have been synthesized. The particles, which retained the face centered cubic (fcc) symmetry of the original bulk metals, together with the graphitic coating were characterized by means of aberration corrected scanning transmission electron microscopy (STEM), obtaining mean particle sizes of 2.6 nm and 6.2 nm for NiCo/G and FeNi/G, respectively. Due to the enhancement of the thermal stability by the graphite shell, the graphite coated FeNi and NiCo were stable under oxygen atmosphere up to 170 °C. The effectiveness of the graphite shell was confirmed when unprotected bimetallic FeNi and NiCo were prepared and chemical characterization revealed that more than 60 at.% of the samples was oxygen due to the massive oxidation of the bimetallic nanoparticles.Peer reviewe
Enough of 'tough': Youth Justice in Scotland
No full textHow can we build an effective youth justice system that enjoys public confidence while recognising that children must be redeemable?Nico Juetten presents a view from Scotland, considering the challenges to the children's hearings system Copyright (c) 2009 The Author. Journal compilation (c) 2009 ippr.
Ciò che resta della terza dimensione
No full textThe s.c. «third dimension» is one of the first definitions given in the sociological arena to define the development of a ate element that was not identifiable with generalist instances of the state or with those particularistic of the market. Deriving its conceptualization from the Husserlian theory, Ardigò through the use this approach emphasizing the need to reconstruct the crisis through new forms of transaction between the social system and life-worlds. The use of this conceptualization led to the identification of these intermediary organizations between different systems. The text takes a brief overview of the third dimension organizations and the way how they operate the reconciliation between inter-subjectivity and super-ordination present in the systemic sense. It is proposed a scheme of interpretation, drawn from the author in question, through which classifying not merely the organization but the possible interconnections between micro and macro and their consequences. It is concluded that the abandon of the analytical perspective proposed by Ardigò, primarily for the affirmation of a vision of an economic nature, was determined both by the theoretical vulgate established around of the 90, and the difficulty in operationalizing a definition that owed much to the knowledge from the phenomenology of the Bolognese scientist
Alla ricerca della sovranità nello studio di Carlo Lavagna sulle figure giuridiche soggettive
No full textIl presente contributo ripercorre il saggio di Carlo Lavagna, Basi per uno studio delle figure giuridiche soggettive contenute nella Costituzione italiana, allo scopo di ricercare il filo conduttore della sovranità in tutte le figure giuridiche soggettive sia che esse siano solo raccomandate, sia che siano garantite o anche tutelate dalla Costituzione, secondo la classificazione dell’Autore. Tale analisi è stata preceduta da un breve richiamo al metodo di indagine dell’Autore e alla sua concezione quadrangolare della democrazia.This contribution reinterprets the essay by Carlo Lavagna, Basis for a study of the subjective juridical figures contained in the Italian Constitution, in order to search for the sphere of sovereignty in all subjective legal figures whether they are only recommended, whether they are guaranteed or also protected by the Constitution, according to the classification of the Author. This analysis was preceded by a brief recall of the Author's method of investigation and its quadrangular concept of democracy
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