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Preference-based Flexible Multiobjective Evolutionary AlgorithmsKarahan, Ibrahim 01 June 2008 (has links) (PDF)
In this study,we develop an elitist multiobjective evolutionary algorithm for approximating the Pareto-optimal frontiers of multiobjective optimization problems. The algorithm converges the true Pareto-optimal frontier while keeping the solutions in the population well-spread over the frontier. Diversity of the solutions is maintained by the territory de& / #64257 / ning property of the algorithm rather than using an explicit diversity preservation mechanism. This leads to substantial computational e& / #64259 / ciency. We test the algorithm on commonly used test problems and compare its performance against well-known benchmark algorithms.
In addition to approximating the entire Pareto-optimal frontier,we develop a preference incorporation mechanism to guide the search towards the decision maker& / #8217 / s regions of interest. Based on this mechanism, we implement two variants of the algorithm. The & / #64257 / rst gathers all preference information before the optimization stage to & / #64257 / nd approximations of the desired regions. The second one is an interactive algorithm that focuses on the desired region by interacting with the decision maker during the solution process. Based on tests on 2- and 3-objective problems, we observe that both algorithms converge to the preferred regions.
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Expanding the genetic code in mammalian cellsXiang, Liang 15 January 2013 (has links)
Proteins are diverse polymers of covalently linked amino acids. They play a role in almost every biological process that occurs within an organism. Twenty different amino acids are genetically encoded by mammalian cells to build proteins. The sequence of these amino acids determines the protein’s final shape, structure, and function. Modern molecular cloning techniques allow for the genetic encoding and expression of mutant proteins that have one or more amino acids replaced with one of the others. The roles of individual amino acids in a protein can therefore be studied. Proteins with novel functions have also been designed or evolved using this technology. However, the genetic code is limited to the twenty natural amino acids.
Nonnatural amino acids have unique side groups that not found on any of the twenty natural amino acids. They can be site-specifically incorporated using a mutant orthogonal suppressor tRNA/aminoacyl-tRNA synthetase (aaRS) pair. Each pair only allows for one type of nonnatural amino acid to be genetically encoded. This technology has resulted in the incorporation of over fifty different types of nonnatural amino acids into proteins in prokaryotic and eukaryotic cells. Unfortunately, most of these pairs are not orthogonal outside of prokaryotic systems and only a few have been developed for mammalian cells. To create more mammalian pairs a nonnatural aaRS has to be evolved and screened in a cumbersome process. In this dissertation an approach is outlined that can be used to change the orthogonality of existing nonnatural suppressor tRNA/aaRS pairs. As a result of the orthogonality change many previously unavailable pairs can be shuttled into mammalian cells. The ability to genetically encode a 21st amino acid is a powerful tool in the study and engineering of proteins. / text
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Protein evolution in the presence of an unnatural amino acidSingh, Amrita, active 2012 04 March 2014 (has links)
The field of protein engineering has been greatly augmented by the expansion of the genetic code using unnatural amino acids as well as the development of cell-free synthesis systems with high protein yield. Cell-free synthesis systems have improved considerably since they were first described almost 40 years ago. Residue specific incorporation of non-canonical amino acids into proteins is usually performed in vivo using amino acid auxotrophic strains and replacing the natural amino acid with an unnatural amino acid analog. Herein, we present an amino acid depleted cell-free protein synthesis system that can be used to study residue specific replacement of a natural amino acid by an unnatural amino acid analog. This system combines high protein expression yields with a high level of analog substitution in the target protein. To demonstrate the productivity and efficacy of a cell-free synthesis system for residue-specific incorporation of unnatural amino acids in vitro, we use this system to show that 5-fluorotryptophan and 6-fluorotryptophan substituted streptavidin retain the ability to bind biotin despite protein wide replacement of a natural amino acid for the amino acid analog. We envisage this amino acid-depleted cell-free synthesis system being an economical and convenient format for the high-throughput screening of a myriad of amino acid analogs with a variety of protein targets for the study and functional characterization of proteins substituted with unnatural amino acids when compared to the currently employed in vivo format. We use this amino acid depleted cell-free synthesis system for the directed evolution of streptavidin, a protein that finds wide application in molecular biology and biotechnology. We evolve streptavidin using in vitro compartmentalization in emulsions to bind to desthiobiotin and find, at the conclusion of our experiment, that our evolved streptavidin variants are capable of binding to both biotin and desthiobiotin equally well. We also discover a set of mutations for streptavidin that are potentially powerful stabilizing mutations that we believe will be of great use to the greater research community. / text
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Emerging biotechnology to detect weak and/or transient protein-protein interactionsThibodeaux, Gabrielle Nina 30 April 2014 (has links)
Protein-protein interactions are of great importance to a number of essential biological processes including cell cycle regulation, cell-cell interactions, DNA replication, transcription and translation. Thus, an understanding of protein-protein interactions is critical for understanding many facets of cell function. Unfortunately, the tools and methods currently in use to identify and study protein-protein interactions focus largely on high affinity, stable interactions. However, the majority of the protein-protein interactions involved in regulatory processes have weak affinities and are transient in nature. Therefore, it is important to develop new biotechnology capable of detecting weak and/or transient protein-protein interactions in vivo. Here, we describe four new methods that allow for the identification and study of weak and/or transient protein-protein interactions in vivo. First, we developed a rapid method to convert Escherichia coli orthogonal tRNA/synthetase pairs into an orthogonal system for mammalian cells in order to site-specifically incorporate unnatural amino acids into any gene of interest using stop codon suppression. This method will allow the expression and purification of proteins that carry normally transient post-translational modifications. Second, we successfully employed site-specific unnatural amino acid incorporation to chemically cross-link a known homodimer, Sortase A, in vivo. Third, we developed a novel tetracycline repressor-based mammalian two-hybrid system and successfully detected homo- and hetero-dimers that are known to have weak binding constants. Finally, a synthetic antibody (termed a synbody) that binds weakly to the SH3 domain of the proto-oncogene Abelson tyrosine kinase was developed. The synbody can potentially be used as a first generation drug and/or biomarker. We hope that the methods developed in this dissertation will enable the scientific community to better understand weak/transient protein-protein interactions in vivo. / text
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Förutsättningar för inkorporation : upplevelse av möjlighetÖfors, Hanna January 2015 (has links)
Förutsättningar för inkorporation – upplevelsen av möjligheten är en studie, skriven av Hanna Öfors, som sätter fokus på invandrares upplevelse av sin möjlighet att bli en del av det svenska samhället. Detta har gjorts genom fyra djupintervjuer med invandrare som har kommit till Sverige i vuxen ålder och som kan betraktas som relativt sätt tillfredsställande fall, om deras egna upplevelser. Studiens syfte är att teckna en bild av hur nysvenskar upplever sin inkorporationsprocess och möjlighet till delaktighet i det svenska samhället. Dessutom är studiens strävan att identifiera vilka komponenter som är av betydelse för en upplevelse av delaktighet respektive utanförskap. Den teoretiska referensram som studien utgår ifrån innefattar dels kapitalteori med särskilt fokus på socialt kapital, och dels av teorier om delaktighet och utanförskap samt identitet, vilket har infogats som komplement till dig förstnämnda. Den tidigare forskning som presenteras lyfter fram äktenskap och samboskap som positivt för inkorporationen. Resultatet av undersökningen visar att det är viktigt att individen har ett högt socialt kapital inom minst ett fält för att hen ska kunna känna delaktighet och tillhörighet i det svenska samhället. Att ha ett arbete lyfts av flera informanter fram som extra viktigt för denna möjlighet. Vidare visar resultatet också, vilket understöds av tidigare forskning, att en relation, såsom äktenskapet, innebär ett ökat socialt kapital och därmed ökad möjlighet till delaktighet och tillhörighet i det svenska samhället. Genom att ta reda på vad som förutsätts för att en inkorporationsprocess skall upplevas som tillfredsställande skulle det kunna bli möjligt att påverka diskursen kring invandring och inkorporation i en positiv och mer gynnsam riktning för de individer som framgent kommer till Sverige. / Conditions for incorporation – experience of possibility is a study written by Hanna Öfors. It focuses on immigrants and their experience of the possibility to be included as a part of the Swedish society. This is done, by interviewing four people who moved too Sweden as grownups and whom, relatively speaking, could be looked at as cases of satisfying incorporation, about their experiences of incorporation. The purpose of this study is to investigate and understand how immigrants look at their incorporation process and the degree to which it is possible for them to be a part of the Swedish society. Moreover, it is meant to identify the components that are important for them to feel included in or excluded from the Swedish society. The frame of reference that this study is based on is built on three components, capital theory, concentrated on social capital, and theories about participation, alienation and identity. The three latest terms has added as a complement to capital theory. Recent research says that partnership and marriage has a positive effect on incorporation. The results show that an individual ought to have a large amount of social capital, in at least one field, for them to feel a part of the Swedish society. Employment is pointed out to be an extra important factor for this possibility. It is also shown that a relationship, such as marriage, leads to an increase in social capital. The same results are also proved in earlier studies. By finding what is needed, for an incorporation process to be satisfying, it could be possible to influence the discourse around immigration and incorporation in a positive way. Hopefully this could lead to more favorable conditions for immigrants in the future.
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Effects of moisture on the breakdown strength and lifetime of low permittivity dielectric for nanometer scale interconnectsChoi, Soo Young, doctor of materials science and engineering 13 June 2011 (has links)
Advanced integrated circuit (IC) technology has implemented new materials for necessary and timely performance improvements. New materials are now required at both the front-end-of-line (FEoL) and back-end-of-line (BEoL) of the device because simple dimensional scaling with standard materials has come with performance costs that negate dimensional scaling performance improvements. At the FEoL, high-[kappa]/metal gate processes are being developed to reduce gate oxide leakage. At the BEoL, Cu-based metallization and low-[kappa] dielectric materials have been developed to reduce BEoL contribution to RC-propagation delay. Cu-based metallization has required change in integration strategy, which has led to concerns about new material reliability performance. Furthermore, continuing pressure to improve device performance requires that a new, more advanced low-[kappa] dielectric be used, which are mechanically and electrically inferior. These performance demands and greater reliability concerns must be balanced. This kind of balance requires that better understanding of the extrinsic threats to device reliability be understood and is the general area of interest for this work. In particular, this study examines the extent of degradation found in low-[kappa] dielectric when it is exposed to ambient moisture and the potential impact of this degradation on intrinsic reliability performance under electrical stress. The integration method is described for low-[kappa] dielectric processing so that potential damages during process can be explained. Local damages can allow moisture incorporation at the expense of additional dielectric performance and reliability degradation. The molecular form of moisture incorporation into low-[kappa] dielectric and potential process methods to reduce moisture incorporation are also discussed. The electrical reliability performance is shown using interdigitated structures through voltage ramped dielectric breakdown study of inter-metal dielectric (IMD). Clear evidence of dielectric degradation is found after extreme moisture incorporation. Moisture penetration impact is also examined on the long-term reliability of integrated low-[kappa] dielectric using time-dependent dielectric breakdown (TDDB). Results show a dramatic change in the observed field acceleration parameter through moisture exposure that is not easily explained in a standard way according to proposed dielectric breakdown models for low-[kappa] dielectrics. A simple modification of the thermochemical [Epsilon]-model is proposed to explain the results. / text
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Anglų kalbos gramatinės inkorporacijos procesas ir jo perteikimas lietuvių kalboje / Process of Grammatical Incorporation in English and its Rendering into LithuanianŽukauskienė, Jurgita 31 May 2006 (has links)
SANTRAUKA
Skirtingų kultūrų ir kalbų gausa sąlygoja būtinybę vienos tautos vertybes, mintis ir stilius perteikti kitai, taigi vertimas tampa kultūrinių kontaktų kūrimo ir plėtimo priemone. Kadangi vertimo svarba tarpkultūrinės komunikacijos raidoje nuolat auga, jis susilaukia vis daugiau lingvistų dėmesio. Gramatinė vertimo pusė sukelia eilę sunkumų, todėl geras vertėjas turi ne tik puikiai išmanyti gramatikos taisykles, bet ir gebėti jas taikyti praktiškai bei tinkamai atlikti įvairius pakeitimus, kurie neišvengiami vertimo procese.
Šis darbas skirtas anglų kalbos gramatinės inkorporacijos proceso pristatymui ir jo perteikimo lietuvių kalboje būdų ir ypatumų analizei. Gramatinės inkorporacijos procesas, apibūdina konstrukcijas, kuriose pasak Farkas ir de Swart (2004:1), veiksmažodis ir vienas iš jo argumentų sudaro glaudžiai susietą junginį. Šis fenomenas neretai tampa vertimo sunkumų priežastimi, kadangi yra daug atvejų, kai inkorporacinių konstrukcijų pateikimas originalo ir vertimo kalbose skiriasi leksine ir semantine prasme. Tokie vertimo sunkumai bei jų analizė ir suteikia pagrindą šiam darbui, kuriame gramatinės inkorporacijos konstrukcijos analizuojamos gramatiniu ir vertimo aspektu.
Darbe, naudojantis aprašomuoju, gretinamuoju ir statistiniu metodais, apžvelgta mokslinė literatūra, atskleidžiamos inkorporacinių konstrukcijų ypatybės, pateikiami ir aptariami pavyzdžiai bei analizuojami jų vertimo būdai. Atliktas tyrimas patvirtino hipotezę, kad ne visos... [to full text]
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CO2-SELECTIVE MEMBRANE FOR FUEL CELL APPLICATIONSEl-Azzami, Louei Abdel Raouf 01 January 2006 (has links)
We have developed CO2-selective membranes to purified hydrogen and nitrogenfor fuel cell processes. Hydrogen purification impacts other industries such as ammoniaproduction and flue gas purification at reduced costs.Dense chitosan membranes were used for the first time to separate CO2 from amixture of 10% CO2, 10% H2, and 80% N2 at temperatures of 20 – 150oC and feedpressures of 1.5 atm – 5 atm. At 1.5 atm and 20 – 150oC, dry chitosan membranesachieved CO2 permeabilities, CO2/N2 and CO2/H2 separation factors of 0.383 – 24.3barrers, 10.7 – 3.40, and 4.54 – 1.50, respectively. The dry chitosan acted as an ordinarysolution-diffusion membrane: permeability increased with temperature but selectivitydecreased. The CO2/H2 and CO2/N2 separation factors at all temperatures enhanced CO2removal, making this membrane a candidate for fuel cell processes. The dual modetransport model fitted the transport data well.To achieve higher CO2 transport properties, chitosan was swollen with water.Water mediated the reaction of chitosan's amino groups with CO2. Humidifing the feedand sweep gases increased the membrane's performance. At 1.5 atm and 20 – 110 –150oC, CO2 permeabilities, CO2/N2 and CO2/H2 separation factors were 213 – 483 – 399barrers, 69.4 – 250 – 194, and 18.9 – 43.4 – 29, respectively. The presence of free waterand bound water facilitated the transport of CO2. Increasing feed pressure removed themaxima in permeability and selectivities at 110oC, but led to reduced CO2 permeabilities,CO2/N2 separation factors, and CO2/H2 separation factors to 156 – 286 barrers, 44.2 –131, and 12.0 – 16.7, respectively.To acquire higher CO2 transport properties, arginine-sodium salts wereincorporated in chitosan membranes as additional sites for facilitated transport. The salt'spercolation threshold was 40 wt %. At 1.5 atm and 20 – 110 – 150oC, CO2 permeabilities,CO2/N2 and CO2/H2 separation factors were 403 – 1498 – 1284 barrers, 122 – 852 – 516,and 31.9 – 144 – 75.5, respectively. Increasing feed pressure to 5 atm resulted indeclining CO2 permeabilities, CO2/N2 and CO2/H2 separation factors to 118 – 1078barrers, 21.6 – 352, and 5.67 – 47.9, respectively.Chitosan was characterized in terms of morphology, solution properties, thermalproperties, crystallinity, and degree of deacetylation.
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HOW A SILENT MUTATION SUPPRESSES THE ACTIVITY AND IRON INCORPORATION IN SUPEROXIDE DISMUTASEMei, Xiaonan 01 January 2012 (has links)
A mutation (CTG to TTG) of FeSOD gene was found in Escherichia coli. Since they both encode leucine, it is a silent mutation. Site-‐directed mutagenesis was applied to correct the mutation, and the mutant FeSOD (before gene correction) and wild type FeSOD (after gene correction) were purified. The FeSODs from the two genes were Characterized using different assays and spectroscopic methods including EPR and CD. The requirement for the rare codon TTG may result in slowed translation and heavy demand on a scarce tRNA. Cultures expressing wild type FeSOD are better able to grow for long times after addition of IPTG and more mature to incorporate Fe atoms to the active sites than are cultures expressing the mutant gene. Moreover, the wild type FeSOD has more activity than the mutant. To our knowledge, this is the first time that a silent mutation has been demonstrated to affect metal incorporation into a metalloenzyme.
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The Political Incorporation of Latino Immigrants in CaliforniaRamos, Adriana Janet 01 January 2014 (has links)
This paper explores and analyzes the political incorporation of Latino immigrants in California over the last several decades. Political incorporation refers to the process through which immigrants and their descendants claim their political rights and exercise their voice in politics. In order to understand the impact of Latino immigration on California state politics, the paper first examines the demographic changes in the state. This paper then provides an overview of all of the major immigration legislation in California, beginning from the anti-immigration initiatives to the California Dream Act and immigration-friendly legislation that Governor Jerry Brown signed into law in 2013.
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