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1

Hui, Daniel Jason. "The Mechanism of Protein Synthesis Inhibition by the P56 Family of Viral Stress Inducible Proteins". Connect to text online, 2005. http://rave.ohiolink.edu/etdc/view?acc%5Fnum=case1104848977.

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2

Braute, Petter, i Jorg Eliassen Rødsjø. "Protein function prediction using annotated protein-protein interaction networks". Thesis, Norwegian University of Science and Technology, Department of Computer and Information Science, 2005. http://urn.kb.se/resolve?urn=urn:nbn:no:ntnu:diva-9177.

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3

Pereira, Joice Naiara Bertaglia. "Avaliação morfoquantitativa e ultraestrutural da cartilagem do processo condilar da mandíbula e da sincondrose basioccipital de ratos Wistar subnutridos e suplementados com resveratrol". Universidade de São Paulo, 2015. http://www.teses.usp.br/teses/disponiveis/10/10132/tde-16122015-121456/.

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A subnutrição é uma doença causada pela ingestão inadequada e/ou insuficiente de energia ou de outras biomoléculas, que pode comprometer o crescimento e o desenvolvimento dos tecidos. Em conjunto, a cartilagem do processo condilar da mandíbula e a sincondrose basioccipital representam os dois centros efetivos do crescimento craniofacial, que depende, dentre outros, de fatores locais como a produção do fator de crescimento semelhante à insulina I (IGF-I) e seu receptor (IGF-IR). Alterações tanto no peptídeo quanto no receptor estão associadas a graves atrasos no crescimento e desenvolvimento ósseo. Dentre os nutrientes alternativos com a capacidade de promoção da recuperação nutricional, destaca-se o resveratrol, um polifenol contido na uva e derivados que pode promover a melhora do crescimento através de propriedades osteogênicas, além de atuar como condroprotetor. Assim, a presente pesquisa teve por objetivo avaliar os efeitos da subnutrição proteica na cartilagem do processo condilar da mandíbula (PC) e na sincondrose basioccipital (SBo) de ratos, bem como os processos de renutrição e suplementação com resveratrol nos períodos pré-púbere (21 dias) e púbere (60 dias). Os grupos nutrido (N) e subnutrido (S) foram formados por filhotes cujas mães receberam dieta normoproteica e hipoproteica, respectivamente, desde o período de acasalamento; ao completarem 21 dias de vida extrauterina, época determinada para o desmame, os filhotes foram eutanasiados. A partir do 22° dia de vida, filhotes dos grupos N e S foram mantidos com as respectivas dietas até o 60° dia de vida quando constituíram, respectivamente, os grupos NN e SS. Dois grupos considerados renutridos foram formados por animais do grupo S, que a partir do 22° dia passaram a receber, o primeiro, a dieta normoproteica com 20% de caseína (grupo RN), e o segundo, a dieta normoproteica acrescida de resveratrol (RRv). A cartilagem do PC e a SBo foram processadas através das técnicas histológicas rotineiras e posteriormente submetidas às colorações da HE, Picrossíruis e Safranina-O, para a evidenciação dos componentes celular e colágeno e imunohistoquímica para a marcação de células reativas ao IGF-I e IGF-IR. Os aspectos ultraestruturais também foram analisados através da microscopia eletrônica de transmissão. Os resultados mostraram que a subnutrição foi capaz de alterar os componentes da matriz extracelular (MEC), acarretando em modificações na secreção das fibrilas colágenas e acúmulo de proteoglicanas nos tecidos; diminuição do número de células imunorreativas ao IGF-I e IGF-IR na cartilagem do PC e atraso no crescimento ósseo endocondral, comprovado através das avaliações quantitativas e morfométricas, em ambos os tecidos. A renutrição com dieta normal foi parcialmente eficaz na recuperação dos parâmetros avaliados, e pode ter provocado uma diminuição da capacidade de resposta celular ao IGF-I. Os efeitos condroprotetores do resveratrol foram fundamentados através da recuperação dos componentes da MEC e organelas dos condrócitos e uma possível diminuição da insensibilidade ao IGF-I; o atraso no crescimento ósseo endocondral foi minimizado através do seu potencial osteogênico (mais acentuado na SBo). Muito embora a recuperação dos tecidos não tenha ocorrido totalmente, diante dos dados apresentados, pode-se afirmar que a suplementação de resveratrol na dieta auxiliou de forma mais efetiva no restabelecimento dos parâmetros afetados pela subnutrição do que somente a recuperação proteica com dieta normal
Undernutrition is a disease caused by inadequate and / or insufficient intake of energy or other biomolecules, which can compromise growth and development of tissues. Together, the mandibular condylar cartilage and basioccipital synchondrosis represent the two effective centers of craniofacial growth, which depends of the factors such as the local production of insulin like growth factor I (IGF-I) and receptor (IGF-IR). Changes in both the peptide and receptor are associated with serious delays in growth and bone development. Among the alternative nutrients to the promotion capacity of nutritional recovery, there is resveratrol, a polyphenol contained in grapes and derivatives that can promote improved growth through osteogenic properties, besides acting as chondroprotective. Thus, the present study aimed to evaluate in rats the effects of protein undernutrition in the mandibular condylar cartilage and basioccipital synchondrosis, as well renutrition and supplementation with resveratrol in pre pubertal periods (21 days) and pubertal (60 days). The nourished groups (N) and undernourished (S) were formed by young whose mothers received normal protein and hypoproteic diet respectively since the breeding season; to complete 21 days of extra-uterine life, given time to weaning, puppies were euthanized. From the 22nd day of life, puppies from N and S groups were kept with their diets until the 60th day of life when constituted, respectively, NN and SS groups. Two groups considered re-nourished were formed by the S group, which from day 22 began receiving, the first, the normal protein diet with 20% casein (RN group), and the second, the normal protein diet plus of resveratrol (RRv). The cartilage of PC and SBo were processed through routine histological techniques, and then subjected to HE, Sirius red and Safranin-O staining for the disclosure of cellular components and collagen and immunohistochemistry for marking cells responsive to IGF-I and IGF-IR. The ultrastructural aspects were also analyzed by transmission electron microscopy. The results showed that undernutrition was able to change the components of the extracellular matrix (ECM) leading to changes in the secretion of collagen fibrils and proteoglycans accumulation in the tissues; decrease in the number of immunoreactive cells to IGF-I and IGF-IR in PC cartilage and delayed endochondral bone growth, confirmed by quantitative and morphometric analysis in both tissues. Renutrition with normal diet was partially effective in recovering the parameters evaluated, and may have caused a decrease in cell responsiveness to IGF-I. The chondroprotective effects of resveratrol were founded by recovering the ECM components and organelles of chondrocytes and a possible decrease in the insensitivity to IGF-I; the delay in endochondral bone growth was minimized by osteogenic potential (more pronounced in SBo). Although the tissue recovery has not fully occurred, the resveratrol supplementation in the diet helped more effectively in restoring the parameters affected by undernutrition than just protein recovery with normal diet
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4

Treptow, Till. "Identifizierung und Charakterisierung zweier neuer Proteine, die mit dem HIV-Rev-Protein interagieren". Diss., lmu, 2009. http://nbn-resolving.de/urn:nbn:de:bvb:19-109373.

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5

Bardeleben, Anna Christina von. "Identifikation von neuen Schlitzmembranproteinen: NEPH-Proteine interagieren mit dem PDZ-Domänen-Protein PICK1". [S.l. : s.n.], 2008. http://nbn-resolving.de/urn:nbn:de:bsz:25-opus-55735.

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6

Maschkowitz, Gregor [Verfasser]. "Untersuchung der Protein-Protein-Interaktion der Proteine ppUL35 und ppUL35A des humanen Cytomegalievirus mit dem zellulären Protein Sorting Nexin 5 / Gregor Maschkowitz". Kiel : Universitätsbibliothek Kiel, 2017. http://d-nb.info/1138979988/34.

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7

Laborenz, Janina [Verfasser], i Johannes [Akademischer Betreuer] Herrmann. "Ema19 - ein ER-Protein mit Relevanz für mitochondriale Proteine / Janina Laborenz ; Betreuer: Johannes Herrmann". Kaiserslautern : Technische Universität Kaiserslautern, 2020. http://d-nb.info/1224474880/34.

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8

Franz, Martin [Verfasser]. "Vermehrung und Analyse des abnormalen Prion-Proteins mit Hilfe der protein misfolding cyclic amplification / Martin Franz". Greifswald : Universitätsbibliothek Greifswald, 2012. http://d-nb.info/1028232330/34.

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9

Schmidt, Michel. "Recombinant structural proteins of rubella virus". Helsinki : University of Helsinki, 2000. http://ethesis.helsinki.fi/julkaisut/mat/bioti/vk/schmidt/.

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10

Fu, Karen 1967. "Stability of proteins within biodegradable microspheres". Thesis, Massachusetts Institute of Technology, 2000. http://hdl.handle.net/1721.1/8422.

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Thesis (Sc.D.)--Harvard--Massachusetts Institute of Technology Division of Health Sciences and Technology, 2000.
Includes bibliographical references.
In the past decade, biodegradable polymers have become the materials of choice for a variety of biomaterials applications. In particular, poly(lactic-co-glycolic acid) (PLGA) microspheres have been extensively studied for controlled-release protein delivery. However, significant issues arise in formulating such delivery systems since few proteins have been successfully encapsulated and released from these microspheres. Here, methods are developed to determine the causes of protein instability and solutions are provided for overcoming these problems. A commonly used technique for protein encapsulation in PLGA microspheres is the double-emulsion method. The harsh processing associated with this method can cause denaturation of the encapsulated protein. Herein, we have used Fourier transform infrared (FTIR) spectroscopy to determine the secondary structures of two model proteins, bovine serum albumin (BSA) and chicken egg-white lysozyme, within PLGA microspheres. This is a novel technique for in situ evaluation of proteins within microspheres and potentially a powerful and quick method for assessment of formulations. Results for both proteins indicate changes in structure upon entrapment within the microspheres. However, addition of the stabilizing excipient trehalose prevents the denaturing effects incurred during processing. In addition, BSA released from microspheres is improved by incorporation of trehalose. With microspheres made by double emulsion, there is often a large, initial burst of drug release upon injection. This results in inefficient use of therapy. To prevent this loss, a modified spontaneous emulsification method was explored.
(cont.) With this procedure both protein and polymer are soluble in a single solvent system thus avoiding creation of a water/solvent interface. The process was optimized for microsphere size and protein loading. Addition of a charged surfactant served to improve protein solubility and thus increase protein loading. In vitro and in vivo release kinetics showed a minimal burst, lower than that found with double emulsion microspheres, followed by sustained release. Upon injection of the microspheres in vivo, the PLGA microspheres begin to degrade. Degradation of the polymer generates acidic monomers, and acidification of the inner polymer environment is a central issue in the development of these devices for drug delivery. To quantitatively determine the intraparticle acidity, pH-sensitive fluorescent dyes were entrapped within the microspheres and imaged with confocal fluorescence microscopy. The technique allows visualization of the spatial and temporal distribution of pH within the degrading microspheres. The data indicate the formation of a very acidic environment within the particles with the minimum pH as low as 1.5. The images show a pH gradient, with the most acidic environment at the center of the spheres and higher pH near the edges, which is characteristic of diffusion-controlled release of the acidic degradation products. Strategies to avoid the accumulation of acidic monomers involve decreasing the diffusion distance of the degradation products by either decreasing the overall diameter of the microspheres or creating porous particles.
by Karen Fu.
Sc.D.
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11

Durrant, Michael 1982. "Differential regulation of c-Cbl and Cbl-b ubiquitin ligases downstream of the Met receptor tyrosine kinase". Thesis, McGill University, 2007. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=112619.

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The Cbl family of E3 ubiquitin ligases are important negative regulators of multiple receptor and cytoplasmic tyrosine kinases, and participate in a wide variety of cellular processes. Uncoupling of Cbl-mediated negative regulation allows activated receptor tyrosine kinases such as the Met receptor to escape degradation, enhancing their oncogenic potential in vitro and in vivo. Despite the consequences of loss of Cbl-mediated negative regulation for human disease, little is known about the mechanisms regulating Cbl protein levels themselves.
In this thesis work, I demonstrate a differential regulation of c-Cbl and Cbl-b downstream of the Met receptor tyrosine kinase. Cbl-b protein levels decrease in response to Met kinase activity, whereas c-Cbl levels remain stable. Cbl-b is partially degraded in a proteasome-dependant manner. This requires Cbl-b ubiquitin ligase activity and a carboxy terminal domain region located between the RING and UBA domains. I conclude that the regulation of c-Cbl and Cbl-b differs downstream of Met, and propose that negative regulation of Cbl-b by a dysregulated Met receptor may contribute to tumourigenesis.
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12

Tarkka, Mika. "Developmentally regulated proteins in Pinus sylvestris roots and ectomycorrhiza". Helsinki : University of Helsinki, 2001. http://ethesis.helsinki.fi/julkaisut/mat/bioti/vk/tarkka/.

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13

Kallio-Kokko, Hannimari. "Recombinant hantavirus proteins : antigenic properties and diagnostic applications". Helsinki : University of Helsinki, 2000. http://ethesis.helsinki.fi/julkaisut/mat/bioti/vk/kallio-kokko/.

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14

Thomas, Christian [Verfasser], i Hermann [Akademischer Betreuer] Pavenstädt. "Charakterisierung der Interaktion des KIBRA-Proteins mit der Protein-Kinase M Zeta (PKM Zeta) / Christian Thomas ; Betreuer: Hermann Pavenstädt". Münster : Universitäts- und Landesbibliothek Münster, 2015. http://d-nb.info/1138279900/34.

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15

Pääkkönen, Kimmo. "Applications of residual dipolar couplings in structural studies of proteins". Helsinki : University of Helsinki, 2003. http://ethesis.helsinki.fi/julkaisut/mat/bioti/vk/paakkonen/.

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16

Klæboe, Espen. "Searching for, and identifying Protein Information in the Literature". Thesis, Norges teknisk-naturvitenskapelige universitet, Institutt for datateknikk og informasjonsvitenskap, 2010. http://urn.kb.se/resolve?urn=urn:nbn:no:ntnu:diva-11977.

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As research papers grow in volume and in quantity, there is still to this day, a hassle to locate desired articles based on specific protein names and/or Protein-Protein-Interactions. This is due to the everlasting problem of extracting protein names and Protein-Protein-Interactions from bio-medical papers and articles. The goal of this thesis was to investigate an approach that suggests the use of the Lucene framework for storing and indexing different articles found in bio-medical databases and being able to effciently identify protein names and possible interactions that exist in them. The system, dubbed MasterPPI, locates protein names and Protein-Protein-Interaction keywords with the help of two dictionaries, and when these are found and labeled, determins a Protein-Protein-Interaction if a specific interaction-keyword is present in a sentence, between to protein names. When tested against the test collection from the IAS subtask in the BioCreAtIvE2 challenge; the prototype system achieved a f-score of 0.34, showing that the system has potential, but needs a great deal of work.
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17

Korsisaari, Nina. "Functional analysis of Cdk7-interacting proteins Mat1 and Hint in model organisms". Helsinki : University of Helsinki, 2002. http://ethesis.helsinki.fi/julkaisut/mat/bioti/vk/korsisaari/.

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18

Scott, Mark Andrew Ph D. Massachusetts Institute of Technology. "Ultra-rapid 2-D and 3-D laser microprinting of proteins". Thesis, Massachusetts Institute of Technology, 2013. http://hdl.handle.net/1721.1/79248.

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Thesis (Ph. D. in Electrical and Medical Engineering)--Harvard-MIT Program in Health Sciences and Technology, 2013.
Cataloged from PDF version of thesis.
Includes bibliographical references (p. 124-135).
When viewed under the microscope, biological tissues reveal an exquisite microarchitecture. These complex patterns arise during development, as cells interact with a multitude of chemical and mechanical cues in the surrounding extracellular matrix. Tissue engineers have sought for decades to repair or replace damaged tissue, often relying on porous scaffolds as an artificial extracellular matrix to support cell development. However, these grafts are unable to recapitulate the complexity of the in vivo environment, limiting our ability to regenerate functional tissue. Biomedical engineers have developed several methods for printing two- and three-dimensional patterns of proteins for studying and directing cell development. Of these methods, laser microprinting of proteins has shown the most promise for printing sub-cellular resolution gradients of cues, but the photochemistry remains too slow to enable large-scale applications for screening and therapeutics In this work, we demonstrate a novel high-speed photochemistry based on multi-photon photobleaching of fluorescein, and we build the fastest 2-D and 3-D laser microprinter for proteins to date. First, we show that multiphoton photobleaching of a deoxygenated solution of biotin-4-fluorescein onto a PEG monolayer with acrylate end-group can enable print speeds of almost 20 million pixels per second at 600 nanometer resolution. We discovered that the mechanism of fluorescein photobleaching evolves from a 2-photon to 3- and 4-photon regime at higher laser intensities, unlocking faster printing kinetics. Using this 2-D printing system, we develop a novel triangle-ratchet method for directing the polarization of single hippocampal neurons. This ability to determine which neurite becomes an axon, and which neuritis become dendrites is an essential step for developing defined in vitro neural networks. Next, we modify our multiphoton photobleaching system to print in three dimensions. For the first time, we demonstrate 3-D printing of full length proteins in collagen, fibrin and gelatin methacrylate scaffolds, as well as printing in agarose and agarose methacrylate scaffolds. We also present a novel method for 3-D printing collagen scaffolds at unprecedented speeds, up to 14 layers per second, generating complex shapes in seconds with sub-micron resolution. Finally, we demonstrate that 3-D printing of scaffold architecture and protein cues inside the scaffold can be combined, for the first time enabling structures with complex sub-micron architectures and chemical cues for directing development. We believe that the ultra-rapid printing technology presented in this thesis will be a key enabler in the development of complex, artificially engineered tissues and organs.
by Mark Andrew Scott.
Ph.D.in Electrical and Medical Engineering
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19

Feldmann, Anke. "Entwicklung kapillarelektrophoretischer Trennungen für die Proteinanalytik in Kombination mit dem Elektrosprayionisations-Flugzeit-Massenspektrometer". Doctoral thesis, Technische Universitaet Bergakademie Freiberg Universitaetsbibliothek "Georgius Agricola&quot, 2009. http://nbn-resolving.de/urn:nbn:de:swb:105-013872.

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Um Proteine und Peptide ohne Verluste in der Trennleistung mit Hilfe der Kapillarelektrophorese zu analysieren, wurde der Innenkanal von fused silica Kapillaren mit 2-Hydroxyethylmethacrylat (HEMA) nach dem Prinzip der radikalischen Atomtransferpolymerisation beschichtet. Durch die Variation einiger Reaktionsparameter konnten dabei vier HEMA-Beschichtungen erhalten werden. Mit diesen wurden dann nach den Methoden der Kapillarzonenelektrophorese bei pH 3 und pH 9 und der isoelektrischen Fokussierung Vergleichsmessungen durchgeführt. Die Detektion erfolgte dabei teilweise mit einem Elektrosprayionisations-Flugzeit-Massenspektrometer. Es stellte sich heraus, dass sich die entwickelten Kapillarbeschichtungen im Bezug auf Trenneffizienz wie auch Stabilität im basischen Bereich teilweise stark voneinander unterschieden. Die Betrachtung der Polymerschichten mit Hilfe der Atomkraftmikroskopie zeigte, dass die Morphologie der HEMA-Beschichtung stark vom gewählten Reaktionsmedium abhängig ist.
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20

Muso, Taro M. (Taro Michael). "Green fluorescent protein as a mechanical sensor". Thesis, Massachusetts Institute of Technology, 2007. http://hdl.handle.net/1721.1/39735.

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Thesis (S.M.)--Harvard-MIT Division of Health Sciences and Technology, 2007.
Includes bibliographical references (p. 133-141).
Inquiry into intracellular and cytoskeletal mechanics requires an intracellular mechanical sensor to verify models of sub-cellular structure dynamics. To this end, the green fluorescent protein (GFP) is considered as a mechanical sensor candidate with many desirable characteristics. Implicit solvent molecular dynamics CHARMM simulations demonstrated details inaccessible by AFM and OT methods, such as the linkage dependency of fluorophore environment changes and the energy exchanges between protein components during protein unfolding. Theoretical considerations and in vitro experiments explored the parameters important to GFP conjugation by N-hydroxysuccinimide (NHS) ester chemistry, and the complexities associated with a polymer approach to a controlled distribution of force across fluorescent proteins in a polyacrylamide (PAM) gel.
by Taro M. Muso.
S.M.
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21

Suopanki, Jaana. "Studies on palmitoyl-protein thioesterase 1 : implications for synaptic functions". Helsinki : University of Helsinki, 2002. http://ethesis.helsinki.fi/julkaisut/mat/bioti/vk/suopanki/.

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22

Müller, Ralf. "Untersuchungen zum Entwicklungspotential der Strukturbestimmung mit experimentellen Triplettphasen /". [S.l. : s.n.], 2001. http://swbplus.bsz-bw.de/bsz094447772abs.htm.

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Mangels, Christian. "Komplexe des Prion-Proteins mit antiprional wirksamen Substanzen". kostenfrei, 2008. http://opus.ub.uni-bayreuth.de/volltexte/2009/441/.

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24

Fahnenschmidt, Monika. "De-novo-synthetisierte Proteine mit Metalloporphyrinkofaktoren". [S.l.] : [s.n.], 2000. http://deposit.ddb.de/cgi-bin/dokserv?idn=959723854.

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25

Hæreid, Mari Lie. "Felles ordbok for identifisering av protein-/genforekomster og interaksjoner i biomedisinske artikkelsammendrag. : muligheter og utfordringer". Thesis, Norwegian University of Science and Technology, Department of Computer and Information Science, 2007. http://urn.kb.se/resolve?urn=urn:nbn:no:ntnu:diva-10361.

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Formålet med denne oppgaven var å se på muligheten for samling av flere annoterings- og interaksjonsdatabaser, for dermed å kunne forbedre identifiseringen av protein-/genforekomster og -interaksjoner i biomedisinske artikkel-sammendrag. For å underbygge vurderingene foretatt i oppgaven er en prototype implementert. Den viser hvordan man kan hente ut aktuell informasjon fra forskjellige annoterings- og interaksjonsdatabaser, og lagre dem i en felles relasjonsdatabase. I prototypen blir relasjonsdatabasen indeksert og det er implementert muligheter for tekstsøk mot indeksen. Resultatet av søk viser protein-/gennavn og/eller -synonymer fra relasjons-databasen, samt tilleggsinformasjon som symbol/id, interaksjoner med andre protein/gen og kryssreferanser mellom annoteringsdatabasene. For å teste om prototypen fungere som ønsket og at relasjonsdatabasen lagrer informasjon på en tilfredsstillende måte, er det hentet ut testsett fra annoterings- og interaksjonsdatabasene.Testresultatene viser at informasjon blir lagret, indeksert og kan gjenfinnes på en måte som oppfyller de stilte kravene. Vurderingene som er foretatt, sammen med prototypen, viser at en felles relasjonsdatabase vil være mulig og kan fungere bra for identifisering av protein-/genforekomster i artikkelsammendrag. Til tross for dette er det mange utfordringer som gjenstår før en slik samling vil fungere optimalt. Blant annet er mange av annoterings- og interaksjonsdatabasene forskjellige både i struktur og innhold, samt at det av forskjellige grunner kan være vanskelig å hente ut data fra dem. Dette er også mye av grunnen til at lite forskning er utført innenfor dette området og at det må vurderes hvorvidt det er hensiktsmessig og forsette arbeidet med å utvikle en slik samling, med tanke på ressursbruk og hva man kan få igjen for det.

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26

McGrath, James L. (James Lionel). "Actin dynamics in the cell cytoplasm and the role of actin associated proteins". Thesis, Massachusetts Institute of Technology, 1998. http://hdl.handle.net/1721.1/50446.

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27

Salminen, Outi. "Effect of nicotine on dopaminergic neurotransmission and expression of fos protein". Helsinki : University of Helsinki, 2000. http://ethesis.helsinki.fi/julkaisut/mat/farma/vk/salminen/.

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28

Schlosser, Andreas. "Analyse der Proteinphosphorylierung und anderer kovalenter Proteinmodifikationen mit Elektrospray-Massenspektrometrie". [S.l. : s.n.], 2002. http://deposit.ddb.de/cgi-bin/dokserv?idn=966105931.

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29

Elsässer, Celine. "EPR-Methoden zur Strukturbestimmung von Proteinen mit dipolar gekoppelten Spinzentren". [S.l. : s.n.], 2004. http://www.diss.fu-berlin.de/2004/238/index.html.

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30

Fages, Carol. "mRNA localization and cell motility : roles of heparin-binding proteins amphoterin and HG-GAM in cell migration". Helsinki : University of Helsinki, 2000. http://ethesis.helsinki.fi/julkaisut/mat/bioti/vk/fages/.

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31

Milwid, Jack Miles. "Discovery of novel anti-inflammatory proteins inspired by bone marrow mesenchymal stem cell secretions". Thesis, Massachusetts Institute of Technology, 2011. http://hdl.handle.net/1721.1/68517.

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Streszczenie:
Thesis (Ph. D.)--Harvard-MIT Division of Health Sciences and Technology, 2011.
Cataloged from PDF version of thesis.
Includes bibliographical references (p. 114-133).
Bone marrow mesenchymal stem cells (MSCs) may soon become the first FDA-approved stem cell therapy for autoimmune and inflammatory disease. Our lab originally hypothesized that much of the therapeutic activity of MSCs may be attributed to molecules secreted by these cells. This thesis will test this hypothesis, with an emphasis on translational steps towards clinical product development, including the identification of novel proteins secreted by MSCs. The first part of the thesis consists of studies we performed to test whether MSC conditioned medium (MSC-CM) can treat rats undergoing cisplatin-induced acute kidney injury (AKI). When AKI rats were treated with MSC-CM, we observed a survival benefit and significant protection of renal function compared to controls. The second part of the thesis will describe the development of a device designed for sustained delivery of MSC secreted factors to dialysis-dependent AKI subjects. We tested these devices for cell function, stability and viability when subjected to conditions that model future clinical operation. Finally, inspired by the therapeutic capacity of MSC secreted factors, this thesis will conclude with the introduction of a new method that we developed to uncover novel anti-inflammatory proteins from MSCs. This method revealed four previously unidentified cytokine modulators, two of which we found significantly promote IL-1 0 and suppress TNF-a in mice challenged with endotoxin. When leveraged as novel therapeutics for lethal endotoxemic shock, these two most potent modulators protected mice and provided for a significant survival benefit compared to vehicle controls. Together, these results demonstrate the power of MSC secreted factors in the context of inflammatory disease, and propose new tactics for elucidating potent secreted products from cells.
by Jack Miles Milwid.
Ph.D.
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Peng, Anthony Wei. "A hair bundle proteomics approach to discovering actin regulatory proteins in inner ear stereocilia". Thesis, Massachusetts Institute of Technology, 2009. http://hdl.handle.net/1721.1/54588.

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Thesis (Ph. D.)--Harvard-MIT Division of Health Sciences and Technology, 2009.
Cataloged from PDF version of thesis.
Includes bibliographical references (p. 137-154).
Because there is little knowledge in the areas of stereocilia development, maintenance, and function in the hearing system, I decided to pursue a proteomics-based approach to discover proteins that play a role in stereocilia function. I employed a modified "twist-off" technique to isolate hair bundle proteins, and I developed a method to purify proteins and to process them for analysis using multi-dimensional protein identification technology (MudPIT). The MudPIT analysis yielded a substantial list of proteins. I verified the presence of 21 out of 34 (62%) existing proteins known to be present in stereocilia. This provided strong evidence that my proteomics approach was efficient in identifying hair bundle proteins. Next, I selected three proteins and localized them to murine cochlear stereocilia. StarD10, a putative phospholipid binding protein, was detectable along the shaft of stereocilia. Nebulin, a putative F-actin regulator, was located toward the base of stereocilia. Finally, twinfilin 2, a putative modulator of actin polymerization, was found at the tips of stereocilia. In order to determine the function of twinfilin 2, I localized the protein predominately to the tips of shorter stereocilia where it is up-regulated during the final phase of elongation. When overexpressed, I found that twinfilin 2 causes a shortening of microvilli in LLC-PK1/CL4 cells and in native cochlear stereocilia. The main result of this thesis was determining the sub-cellular localization of three interesting proteins and functionally characterizing one protein. My thesis also confirmed the proteomics screen I developed as an efficient method for identifying proteins in stereocilia.
by Anthony Wei Peng.
Ph.D.
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Hofmann, Michael. "RESOLFT-Mikroskopie mit photoschaltbaren Proteinen". [S.l. : s.n.], 2007. http://nbn-resolving.de/urn:nbn:de:bsz:16-opus-79385.

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Herrig, Wolfgang Alexander. "Wechselwirkung von Ezrin mit PIP2-haltigen artifiziellen Membransystemen und mit F-Aktin". kostenfrei, 2007. http://www.opus-bayern.de/uni-regensburg/volltexte/2008/817/.

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Tossavainen, Helena. "NMR spectroscopic structure determination of calerythrin, and EF-hand protein from S. erythraea". Helsinki : University of Helsinki, 2003. http://ethesis.helsinki.fi/julkaisut/mat/kemia/vk/tossavainen/.

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Kemper, Christian. "Biogenese mitochondrialer Proteine mit C-terminalem Anker". Diss., kostenfrei, 2008. http://edoc.ub.uni-muenchen.de/8949/.

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Kiel, Christina. "Untersuchung von Ras, Effektor-Komplexen mit gezielt veränderten elektrostatischen Eigenschaften". [S.l.] : [s.n.], 2003. http://deposit.ddb.de/cgi-bin/dokserv?idn=968685927.

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Zerr, Helena [Verfasser]. "Einfluß des surfactantassoziierten Proteins B auf die Aufnahme von Lipiden in Typ II-Zellen im Vergleich mit und ohne das surfactantassoziierte Protein A / Helena Zerr". Berlin : Medizinische Fakultät Charité - Universitätsmedizin Berlin, 2007. http://d-nb.info/1022592556/34.

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Seppä, Tiina. "Role of nicotinic acetylcholine receptors in cerebral dopaminergic transmission and expression of Fos protein". Helsinki : University of Helsinki, 2001. http://ethesis.helsinki.fi/julkaisut/mat/farma/vk/seppa/.

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Tähtiharju, Sari. "The role of calcium and protein phosphatases in cold signal transduction in Arabidopsis thaliana". Helsinki : University of Helsinki, 2002. http://ethesis.helsinki.fi/julkaisut/mat/bioti/vk/tahtiharju/.

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Kiessig, Steffen. "Untersuchung von Protein-Ligand-Interaktionen mit Affinitätskapillarelektrophorese". [S.l. : s.n.], 2001. http://deposit.ddb.de/cgi-bin/dokserv?idn=964716801.

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Steller, Sigrid. "Analyse von Neisseria meningitidis mit Protein-Microarrays". [S.l.] : [s.n.], 2005. http://www.diss.fu-berlin.de/2005/88/index.html.

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Claußen, Holger. "Effizientes Protein-Ligand-Docking mit flexiblen Proteinstrukturen /". Sankt Augustin : GMD-Forschungszentrum Informationstechnik, 2001. http://www.gbv.de/dms/bs/toc/33264023X.pdf.

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44

Wieske, Martin. "Beiträge zur Struktur und Funktion des kleinen Säuger-Streßproteins HSP25 unter besonderer Berücksichtigung der Wechselwirkung mit Actin". Doctoral thesis, Humboldt-Universität zu Berlin, Mathematisch-Naturwissenschaftliche Fakultät I, 1998. http://dx.doi.org/10.18452/14452.

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HSP25 ist ein Vertreter der ubiquitär verbreiteten kleinen Hitzeschockproteine, einer Familie innerhalb der großen Klasse der Streßproteine. Es ist an der Vermittlung von zellulärer Streßtoleranz beteiligt, besitzt Chaperoneigenschaften, hemmt die Actinpolymerisation in vitro und ist in der Lage, supramolekulare Komplexe auszubilden. Die hier vorgelegte Arbeit befaßte sich mit der Isolierung, der strukturellen und funktionellen Charakterisierung des Proteins und seinem Vorkommen in verschiedenen Geweben von Ratten mit pathologisch erhöhtem Blutdruck: · Es wurde eine Methode zur schonenden Isolierung von HSP25 aus Ehrlich-Ascites-Tumor (EAT) etabliert. Daraus konnte niedrig- und hochmolekulares Material gewonnen werden. · Unter Anwendung elektronenmikroskopischer und hydrodynamischer Methoden konnte für die hochmolekularen Komplexe des nativen HSP25 ein Strukturmodell abgeleitet wer-den. Es ist durch eine zylinderförmige Struktur aus vier gestapelten Ringen mit je acht HSP25-Monomeren charakterisiert. · Hochmolekulare Komplexe des rekombinanten HSP25 liegen demgegenüber als kom-pakte globuläre Strukturen vor. Elektronenmikroskopische Analysen verschiedener Mutanten und von phosphoryliertem HSP25 zeigen, daß die HSP25-Komplexe mit zu-nehmender Phosphorylierung kleiner werden. Dies belegt einen Zusammenhang zwischen dem Phosphorylierungszustand des Proteins und seiner supramolekularen Organisation. · Mittels Elektronenmikroskopie und Fluoreszenzspektroskopie konnte gezeigt werden, daß nur natives HSP25 aus EAT, aber nicht rekombinantes HSP25 oder HSP25-Mutanten die Actinpolymerisation hemmen. Dies bestätigt den Befund, daß nur unphosphorylierte nati-ve HSP25-Monomere für die Inhibierung der Actinpolymerisation verantwortlich sind. · Es konnten zwei HSP25-Peptide identifiziert werden, die eine Hemmung der Actinpoly-merisation auslösen. Damit konnte erstmals experimentell nachgewiesen werden, daß be-stimmte Sequenzabschnitte von HSP25 eine spezifische Wechselwirkung mit Actin ein-gehen. Mit Hilfe phosphorylierter HSP25-Peptide konnte die Abhängigkeit dieser Reaktion vom Phosphorylierungszustand bestätigt werden. · Vorläufige Ergebnisse mit Zellulose-gebundenen Peptid-Bibliotheken deuten auf eine Wechselwirkung von HSP25 mit einem exponierten Loop in Actin-Domäne IV hin, einem Bereich, der an Actin-Actin-Wechselwirkungen beteiligt ist. · HSP25 hat aufgrund seiner verstärkten Synthese bei vielen pathologischen Prozessen eine medizinische Relevanz. Untersuchungen an verschiedenen Tiermodellen zeigen, daß es bei Hypertonie-belasteten Herzen verstärkt im rechten Ventrikel akkumuliert wird. · Es wird ein Modell vorgestellt, in dem die Struktur-Funktions-Beziehungen für HSP25 zusammengefaßt sind.
HSP25 is a member of the ubiquitous family of small heat shock proteins belonging to the big class of stress proteins. It is related to acquiring of cellular thermotolerance, can act as molecular chaperone, is able to inhibit polymerization of actin in vitro and can form high molecular weight complexes. In this thesis the isolation, structural and functional characteri-zation of this protein as well as its abundance in different tissues of rats suffering on patho-logical forms of hypertension is analyzed: · A method for rapid isolation of HSP25 out of Ehrlich-ascites-tumor (EAT) was estab-lished. From isolated HSP25 low and high molecular weight material could be obtained. · Analysis of high molecular weight complexes by means of electron microscopy and ana-lytical ultracentrifugation results in a structural model characterized by a cylindrical structure composed of four stacked rings each containing eight HSP25 monomers. · High-molecular weight complexes of recombinant HSP25 are organized as compact globular structures. Electron microscopic investigations of different mutants and of in vi-tro phosphorylated HSP25 show a connection between phosphorylational status and su-pramolecular organization of the protein: the higher the degree of phosphorylation the smaller are the HSP35-complexes. · By means of electron microscopy and fluorescence spectroscopy it could be shown that only native HSP25 from EAT but not recombinant HSP25 nor HSP25 mutants inhibit polymerization of actin. This is in agreement with recent results showing that only un-phosphorylated native HSP25 monomers are active inhibitors of actin polymerization. · Two HSP25 derived peptides could be identified as competent inhibitors of actin polym-erization. This is the first experimental evidence for a specific interaction of HSP25 se-quences with actin. This interaction is dependent on the phosphorylational status as con-firmed by phosphorylated HSP25 peptides. · Preliminary results with cellulose bound peptide libraries indicate an interaction of HSP25 with an exposed loop in actin domain IV, an area involved in actin-actin interactions. · HSP25 is of medical relevance because of its increased synthesis in a bright variety of pathological processes. Investigations on different animal models of hypertension show an enhanced accumulation of HSP25 in the right ventricle. · A model is presented summing up the structure-function relationships of HSP25.
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45

Kieselbach, Brit. "Molekulare Effekte der Immunmodulation mit einem anti-CD4-Antikörper". Doctoral thesis, Humboldt-Universität zu Berlin, Mathematisch-Naturwissenschaftliche Fakultät I, 2004. http://dx.doi.org/10.18452/15074.

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Das grundlegende Problem in der Transplantationsimmunologie ist es, die Langzeitakzeptanz eines fremden (allogen) Organs zu erreichen, ohne die sonstige Immunkompetenz des Empfängers zu beeinträchtigen. Die Induktion einer solchen spenderspezifischen Toleranz würde eine Alternative zum Langzeiteinsatz von Immunsuppressiva darstellen. Deswegen versucht man, während der Transplantation die Aktivierung der für die Abstoßung entscheidenden T-Helferzellen zu unterdrücken, bis eine Akzeptanz des Spenderorgans etabliert ist. Wichtig für eine Aktivierung der T-Zellen ist das für alle T-Helferzellen typische Zelloberflächenmolekül CD4. Antikörper gegen CD4 können in Tiermodellen eine Transplantattoleranz induzieren. Ein besonderes Interesse gilt der Charakterisierung der genauen Mechanismen dieser induzierten Transplantatakzeptanz, da diese noch wenig verstanden sind. Der von uns verwendete nicht-depletierende Maus-anti-Ratten-CD4mAk (RIB5/2) besitzt im allogenen Nierentransplantationsmodell der Ratte eine hohe toleranzinduzierende Wirkung und erzielt eine permanente Transplantatakzeptanz bei >80% der Empfängertiere. In dieser Arbeit wurde versucht, die Effekte dieses monoklonalen Antikörpers auf die T-Zellaktivierung näher zu untersuchen. Ausdruck der blockierten T-Zellaktivierung ist eine verminderte T-Zell-Proliferation und die Reduzierung der Synthese von TH-1-Effektorzytokinen, welche eine zelluläre Immunantwort fördern. Zu diesen für die Abstoßung gefährlichen Th-1-Effektorzytokinen gehören Interleukin 2 (=IL-2, Hauptwachstumsfaktor aktivierter T-Zellen) und Interferon gamma (=IFNgamma, wichtiger Aktivator von APC''s). Während die IL-2 Produktion vollständig verhindert wird, ist die Alloantigen-induzierte IFNgamma mRNA Expression nicht reduziert. Allerdings kommt es unter dem Einfluss des Antikörpers nicht zur IFNgamma Proteinsekretion. Wird jedoch das fehlende IL-2 ersetzt, kann sowohl die defekte Proliferation als auch die posttranskriptionelle Blockade der IFNgamma Produktion wieder aufgehoben werden. Das spiegelt sich auch in vivo wieder, da rekombinantes IL-2 auch hier den Toleranzstatus brechen kann. In dieser Arbeit konnte ein Kandidat dieser IFNgamma Translationskontrolle ermittelt werden. Zusätzlich wurde das Kochaperon p23, Teil eines Hsp90-Komplexes, in unsere Untersuchungen miteinbezogen, da es als ein differentiell reguliertes Gen in allogenen und anti-CD4mAk-behandelten T-Zellen identifiziert wurde. Hsp90 stabilisiert z.B. Kinasen, die wichtige Mediatoren der Signaltransduktion sind. p23 könnte aufgrund seiner Funktion als Kofaktor von Hsp90 an der Regulierung dieser Kinasen beteiligt sein, ist jedoch bisher kaum im Zusammenhang mit T-Zellaktivierung analysiert worden. Meine Untersuchungen ergaben, dass die p23 Expression ebenfalls durch den anti-CD4mAk reduziert wird. Da die Proliferation/p23 und die IFNgamma Synthese IL-2-abhängig reguliert werden, wurden IL-2-induzierte Signalwege auf ihre Relevanz für Proliferation und IFNgamma Regulation hin untersucht. Die Aufklärung der molekularen Mechanismen der anti-CD4mAk-Behandlung auf die T-Zellaktivierung soll mit dazu beitragen, Grundlagen für ein besseres Verständnis des Abstoßungsprozesses und damit Transplantatfunktions-Monitoring zu schaffen.
The major problem in transplantation immunology is the development of long-term donor-specific nonresponsiveness without reduction of the normal recipient immunocompetence. A tolerant state would obviate the need for continuing immunosuppressive therapy. One level of immunosuppression for inducing graft acceptance involves antibodies specific for T-cells of the recipient leading to donorspecific tolerance (e.g. by using of anti-CD4 monoclonal antibodies = aCD4mAb). CD4+ T cells play a predominant role in the cascade of immune processes following transplantation of foreign tissues. The anti-rat CD4 mAb RIB5/2 is very potent in inducing allo-specific tolerance to renal and heart allografts in rat recipients. Here I investigated the molecular mechanisms underlying anti-CD4 antibody mediated inhibition of allo-specific T cell activation and how this is antagonised by exogenous IL-2. IL-2 acts as growth factor for antigen-activated T cells by inducing the expression of cell cycle proteins and also enhances the expression of cytokines, e.g. IFNgamma in T cells. IFNgamma profoundly affects a variety of immune responses, including activation of antigen presenting cells. Anti-CD4 treatment, in vivo and in vitro, completely abrogated IL-2 production by alloreactive T cells. In contrast, anti-CD4 treated allo-activated T cells showed similar IFNgamma mRNA expression as untreated allo-activated T cells, but did not secrete any protein. Thus, the anti-CD4 antibody cannot prevent IFNgamma mRNA expression but is interfering with posttranscriptional mechanisms controlling IFNgamma production during allo-activation of T cells. The investigations revealed a candidate of these IFNgamma translation control. Additionally I investigated the heat shock protein 90 (Hsp90)-associated cochaperone p23. p23 upregulation during T cell activation is also abrogated by anti-CD4 treatment. Hsp90 chaperoning is critical for proper folding, stabilization and trafficking of a number of cellular signaling proteins as e.g. kinases. Hsp90-kinase complexes play an important role in T-cell signal transduction and little is known about the importance or even regulation of Hsp90-cochaperones like p23 during T-cell activation. I analysed the regulation of p23 and downstream effects on different kinases involved in T-cell signaling. These findings are supposed to contribute to a better understanding of the mechanisms underlying tolerance induction.
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46

Schmidt, Joachim. "Das Kinetochorprotein Slk19 Funktion und Interaktion mit der proteasomalen Untereinheit Pre4 /". [S.l. : s.n.], 2005. http://nbn-resolving.de/urn:nbn:de:bsz:93-opus-25022.

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Schmid, Sandra [Verfasser]. "Expression und prognostische Bedeutung verschiedener Proteine im Pankreaskarzinom mit Hauptaugenmerk auf den neuen prognostischen Marker c-FLIP (zelluläres FLICE-inhibitory-Protein) / Sandra Schmid". Ulm : Universität Ulm. Medizinische Fakultät, 2014. http://d-nb.info/1063027047/34.

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Mikhaylova, Yulia. "Wechselwirkung von dünnen Schichten aus HVZ Polyestern im wässrigen Medium mit Modellproteinen". Doctoral thesis, Saechsische Landesbibliothek- Staats- und Universitaetsbibliothek Dresden, 2006. http://nbn-resolving.de/urn:nbn:de:swb:14-1147418427352-93208.

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The dissertation work focuses on the whole route of material development starting from the investigations of properties of the initial (raw) HBPs to their applications. Each research step is given in a separate chapter to enhance attention to various aspects of the aim of the work. Thus, every chapter is started with an introduction. After that, the methods applied and experimental procedure are described. Next part tries to give the comprehensive description of the results obtained. At the end of the chapter, the main points are summarized. The Chapter 1 gives the theoretical description of the main experimental techniques used in this work. In Chapter 2 the chemical (chemical composition, purity, typical structure elements) and physical (glass transition temperature, the temperature of the maximum decomposition, the thermal stability at the high temperatures, molar mass, polydispersity and possible aggregation in solution) properties examined by different techniques of polymer analysis are described. The Chapter 3 is divided into three separate parts: In Chapter 3.1 the description of the formation and modification of inter- and intramolecular hydrogen bonds of hydroxyl terminated HBP is presented to reveal the information of hydroxyl groups re- and/or association due to the high temperatures applied. In Chapter 3.2 the nature of the solid-liquid interface of HBP thin films have been studied by different surface sensitive techniques with respect to further protein adsorption investigations. In Chapter 3.3 the strategy for the fabrication of surface attached carboxyl terminated HBP using "grafting to" technique is developed. The Chapter 4 consists of two parts: The first (theoretic) part outlines the basic principles of protein chemistry, factors influencing on the protein molecule stability in aqueous medium, the mechanism of protein adsorption and forces involved in the adsorption process. In the second part the combination of different in situ techniques was applied to obtain a comprehensive description of complex adsorption processes of protein molecules on different polymer surfaces.
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Grote, Andreas Georg. "Datenbanksysteme und bioinformatische Werkzeuge zur Optimierung biotechnologischer Prozesse mit Pilzen". Paderborn FIT-Verl, 2008. http://d-nb.info/99178541X/04.

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Krämer, Astrid Ursula. "Untersuchungen zur Interaktion von humanem Ras und Rap mit regulatorischen Proteinen". [S.l. : s.n.], 2001. http://deposit.ddb.de/cgi-bin/dokserv?idn=963978993.

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