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Peptide Conjugates as Useful Molecular ToolsŚlósarczyk, Adam T. January 2011 (has links)
The conjugation of a small organic molecule to synthetic polypeptides from a designed set has been shown to give rise to binders with high affinity and selectivity for the phosphorylated model proteins α-casein and β-casein but not for ovoalbumin. The small organic molecule that was used for this purpose is comprised of two di-(2-picolyl)amine groups assembled on a dimethylphenyl scaffold, and is capable of complexing two Zn2+ ions to form chelates that bind the phosphate ion. The designed polypeptides used for binder construction have no precedence in nature and do not show any prior selectivity favouring any single protein. The polypeptide conjugate binders showed high affinity towards the model protein α-casein, the binder molecule 4C15L8-PP1 bound α-casein with a dissociation constant KD of 17 nM, although the di-(2-picolyl) amine based chelate in the presence of Zn2+ bound phosphate ion with dissociation constants in the low mM range. The observed affinity is due to interactions between the Zn2+ chelate and the phosphate groups of α-casein and also to interactions between the polypeptide scaffold and α-casein. The binder was found to selectively extract α-casein from buffer, bovine milk and human serum spiked with α-casein. The flexible construction of the binder permits for flexible modifications like attachment of fluorophores for titrations and quantifications. The binders were shown to efficiently capture α-casein from human serum when immobilized on solid support in a continuous flow system and to release the captured α-casein upon a simple change of pH using 0.1% acqueous trifluoroacetica acid. The developed technology brings new opportunities in investigating posttranslational phosphorylation events that are involved in signaling cascades and triggering many biologically relevant functions. A new chemical linker technology has also been developed for the purpose of conjugating biomolecules taking advantage of amino groups for the conjugation. By combining two esters with different reactivities, separated by an aliphatic chain, a molecular tool was developed that allows for controlled conjugation of biomolecules. The two esters react at different rates and can therefore be separated and allowed to react under different conditions in each step, thereby allowing for selective linkage formation between the subunits. The size of the spacer can be varied by selecting the appropriate dicarboxylic acid. The developed technology was shown to provide specificity in heteroconjugate formation in the assembly of a variety of heteroconjugates where polypeptides were combined with other peptides, carbohydrates and proteins.
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HW/SW mechanisms for instruction fusion, issue and commit in modern u-processorsDeb, Abhishek 03 May 2012 (has links)
In this thesis we have explored the co-designed paradigm to show alternative processor design points. Specifically, we have provided HW/SW mechanisms for instruction fusion, issue and commit for modern processors. We have implemented a co-designed virtual machine monitor that binary translates x86 instructions into RISC like micro-ops. Moreover, the translations are stored as superblocks, which are a trace of basic blocks. These superblocks are further optimized using speculative and non-speculative optimizations. Hardware mechanisms exists in-order to take corrective action in case of misspeculations. During the course of this PhD we have made following contributions.
Firstly, we have provided a novel Programmable Functional unit, in-order to speed up general-purpose applications. The PFU consists of a grid of functional units, similar to CCA, and a distributed internal register file. The inputs of the macro-op are brought from the Physical Register File to the internal register file using a set of moves and a set of loads. A macro-op fusion algorithm fuses micro-ops at runtime. The fusion algorithm is based on a scheduling step that indicates whether the current fused instruction is beneficial or not. The micro-ops corresponding to the macro-ops are stored as control signals in a configuration. The macro-op consists of a configuration ID which helps in locating the configurations. A small configuration cache is present inside the Programmable Functional unit, that holds these configurations. In case of a miss in the configuration cache configurations are loaded from I-Cache. Moreover, in-order to support bulk commit of atomic superblocks that are larger
than the ROB we have proposed a speculative commit mechanism. For this we have proposed a Speculative commit register map table that holds the mappings of the speculatively committed instructions. When all the instructions of the superblock have committed the speculative state is copied to Backend Register Rename Table.
Secondly, we proposed a co-designed in-order processor with with two kinds of accelerators. These FU based accelerators run a pair of fused instructions. We have considered two kinds of instruction fusion. First, we fused a pair of independent loads together into vector loads and execute them on vector load units. For the second kind of instruction fusion we have fused a pair of dependent simple ALU instructions and execute them in Interlock Collapsing ALUs (ICALU). Moreover, we have evaluated performance of various code optimizations such as list-scheduling, load-store telescoping and load hoisting among others. We have compared our co-designed processor with small instruction window out-of-order processors.
Thirdly, we have proposed a co-designed out-of-order processor. Specifically we have reduced complexity in two areas. First
of all, we have co-designed the commit mechanism, that enable bulk commit of atomic superblocks. In this solution we got rid of the conventional ROB, instead we introduce the Superblock Ordering Buffer (SOB). SOB ensures program order is maintained at the granularity of the superblock, by bulk committing the program state. The program state consists of the register state and the memory state. The register state is held in a per superblock register map table, whereas the memory state is held in gated store buffer and updated in bulk. Furthermore, we have tackled the complexity of Out-of-Order issue logic by using FIFOs. We have proposed an enhanced steering heuristic that fixes the inefficiencies of the existing dependence-based heuristic. Moreover, a mechanism to release the FIFO entries earlier is also proposed that further improves the performance of the steering heuristic. / En aquesta tesis hem explorat el paradigma de les màquines issue i commit per processadors actuals. Hem implementat una màquina virtual que tradueix binaris x86 a micro-ops de tipus RISC. Aquestes traduccions es guarden com a superblocks, que en realitat no és més que una traça de virtuals co-dissenyades. En particular, hem proposat mecanismes hw/sw per a la fusió d’instruccions, blocs bàsics. Aquests superblocks s’optimitzen utilitzant optimizacions especualtives i d’altres no speculatives. En cas de les optimizations especulatives es consideren mecanismes per a la gestió de errades en l’especulació. Al llarg d’aquesta tesis s’han fet les següents contribucions:
Primer, hem proposat una nova unitat functional programmable (PFU) per tal de millorar l’execució d’aplicacions de proposit general. La PFU està formada per un conjunt d’unitats funcionals, similar al CCA, amb un banc de registres intern a la PFU distribuït a les unitats funcionals que la composen. Les entrades de la macro-operació que s’executa en la PFU es mouen del banc de registres físic convencional al intern fent servir un conjunt de moves i loads. Un algorisme de fusió combina més micro-operacions en temps d’execució. Aquest algorisme es basa en un pas de planificació que mesura el benefici de les decisions de fusió. Les micro operacions corresponents a la macro operació s’emmagatzemen com a senyals de control en una configuració. Les macro-operacions tenen associat un identificador de configuració que ajuda a localitzar d’aquestes. Una petita cache de configuracions està present dintre de la PFU per tal de guardar-les. En cas de que la configuració no estigui a la cache, les configuracions es carreguen de la cache d’instruccions. Per altre banda, per tal de donar support al commit atòmic dels superblocks que sobrepassen el tamany del ROB s’ha proposat un mecanisme de commit especulatiu. Per aquest mecanisme hem proposat una taula de mapeig especulativa dels registres, que es copia a la taula no especulativa quan totes les instruccions del superblock han comitejat.
Segon, hem proposat un processador en order co-dissenyat que combina dos tipus d’acceleradors. Aquests acceleradors executen un parell d’instruccions fusionades. S’han considerat dos tipus de fusió d’instructions. Primer, combinem un parell de loads independents formant loads vectorials i els executem en una unitat vectorial. Segon, fusionem parells d’instruccions simples d’alu que són dependents i que s’executaran en una Interlock Collapsing ALU (ICALU). Per altra aquestes tecniques les hem evaluat conjuntament amb diverses optimizacions com list scheduling, load-store telescoping i hoisting de loads, entre d’altres. Aquesta proposta ha estat comparada amb un processador fora d’ordre.
Tercer, hem proposat un processador fora d’ordre co-dissenyat efficient reduint-ne la complexitat en dos areas principals. En primer lloc, hem co-disenyat el mecanisme de commit per tal de permetre un eficient commit atòmic del superblocks. En aquesta solució hem substituït el ROB convencional, i en lloc hem introduït el Superblock Ordering Buffer (SOB). El SOB manté l’odre de programa a granularitat de superblock. L’estat del programa consisteix en registres i memòria. L’estat dels registres es manté en una taula per superblock, mentre que l’estat de memòria es guarda en un buffer i s’actulitza atòmicament. La segona gran area de reducció de complexitat considerarada és l’ús de FIFOs a la lògica d’issue. En aquest últim àmbit hem proposat una heurística de distribució que solventa les ineficiències de l’heurística basada en dependències anteriorment proposada. Finalment, i junt amb les FIFOs, s’ha proposat un mecanisme per alliberar les entrades de la FIFO anticipadament.
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Managing aesthetics as open innovation practice : The case study of color and design choice for designed technical productJabeen, Sadia January 2010 (has links)
The purpose of this study is to explore and elaborate how firms are managing aesthetic with color and design choice as open innovation practice and explore its applicability in various sectors. Two research questions are addressed: How is aesthetics with color and design choices managed by firms using open innovation practices? Can aesthetics with color and design choices be managed as open innovation practices for all kinds of technical designed products? The study is based on a case study combined with survey method which constitutes a combination of quantitative and qualitative research for conducting productive research. In order to analyze and explain the case study as open innovation practice for designed technical products, the 4P model of innovation, open innovation model, product design process, digital prototyping and virtual customer environment are used. The survey was used for analyzing the question on generalization for all other designed technical products. The study shows that some mobile firms are using “theme creator”, software for themes that is used for inside aesthetics of designed technical products with customer collaboration and participation. Sony Ericsson is one firm that is establishing activities for outlook aesthetics and inside aesthetics with color and design choice for its designed technical product (mobile). These activities are interpreted as open innovation practices conducted in virtual customer environment by Sony Ericsson. The survey result shows the customer’s willingness for participation and customer’s demand for the change in color and design of designed technical products by their own choice. When combining the case study and survey results it is concluded that color and design choice is required to improve aesthetics for designed technical products.
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Modulinių laukiamojo baldų projektas / Project of the modular lounge furnitureBendikaitė, Renida 02 September 2010 (has links)
Pateikiami trys modulinių laukiamojo baldų variantai. Pagrindinė medžiaga, iš kurios padaryti baldai, yra plastikas. Plastikiniai baldai patogūs, juos paprasta prižiūrėti, lengva pernešti iš vienos vietos į kitą, ir jie yra pigesni. Norint pakeisti baldų išdėstymą nekils problemų. Šiame projekte nėra prisirišama prie plano, moduliniai baldai projektuoti oro uosto laukiamojo salei. Tačiau juos galima pritaikyti ir kitose viešose erdvėse kaip traukinių, autobusų stotis ir t.t.
Atrinktos penkios idėjos, iš kurių trys galutinai išplėtotos. Visuose trijuose variantuose suprojektuotas šviečiantis modulis, centrinis akcentas su vandeniu, ir galimybe atsisėsti.
Pirmajį variantą sudaro šviečiantis elementas bukam kampui, metalinis elementas stačiam kampui, plastikinis elementas smailiam kampui, plastikinė kilpa, šiukšliadėžė, centrinis akcentas. Centrinis akcentas jungia grindis ir lubas, jame įrengtas LED apšvietimas, tekančio vandens atkarpa.
Antrajį variantą sudaro koriuko formos elementai – elementas atsisėsti be atlošo, šviečiantis elementas atsisėsti su atlošu, elementas su jame pasėta žole, šiukšliadėžė, centrinis akcentas. Centrinis akcentas suprojektuotas iš skirtingų dydžių korio formos marmuro plokštumų, jame įrengtas apšvietimas ir vandens telkinys.
Trečiajį variantą sudaro sėdimoji dalis, šviečiantis elementas, šiukšliadėžė, centrinis akcentas. Centriniame akcente įrengtas fontanas, padaryti platesni fontano kraštai, kad būtų galima prisėsti. Po sėdimosios dalies... [toliau žr. visą tekstą] / Three variations of the modular lounge furniture are presented. The main material used to make furniture is plastic. Plastic furniture is comfortable and cheaper. It is easy to handle and move from one place to another. Therefore the change of furniture arrangement does not cause any problems. This project does not accurately follow the plan; modular furniture was designed for the airport departue lounge, but it can be adjusted to use in other public space, such as ralway or bus station, etc. Five ideas were chosen and three of them were developed till the end. All three variations include a luminous module as a central part with water and sitting possibility designed. The first variation consists of luminous element for a blunt corner, metal element for a sharp corner, plastic element for an acute corner, plastic loop, litterbin and a central part. Central part ties in a floor with a ceiling, it includes LED ilumination and running water segment installed. The second variation consists of the comb form elements – sitting element without a backrest, luminous sitting element with a backrest, element with a grass inside it, litterbin and a central part. Central part is designed using different sizes of the comb form marble flats with illumination and water body installed. The third variation consists of the sitting part, luminous element, litterbin and central part. Central part includes a fountain with wide edges to sit on. Illumination is installed under the sitting part.
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Blurred lines: reinvestigating the design possibilites of architecturalized furniture and furniturized architecture in contemporary housingPierce, Allen Carl 22 May 2014 (has links)
Blurred LInes seeks to reopen discussion of the scale and interrelation of architecture and furniture, traditionally conceived. It traces the recent history of furniture and architectural making from the high-point of the “built-in” through the manufacturing age, questioning the corresponding stratification of our immediate built environment into building, infill and objects. Engaging modernist and contemporary criticism, it explores a return to unified building in which the architecture might well become the furniture and vice-versa, erasing built hierarchy and asynchronicity. The paper describes lessons learned from modern masters of the discipline from Adolf Loos to Nader Tehrani and attempts to identify key formal, spatial and constructional considerations in the successful integration and “blurring” of this line. All of this comes to bear in the establishment of design experiments to be carried out in studio, testing the possibilities and viability of the paper's theoretical models.
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Detergents as Membrane-mimetic Media for Structural Characterization of Membrane ProteinsTulumello, David 31 August 2012 (has links)
Membrane proteins are essential cellular components, responsible for a wide variety of biological functions. In order to better understand such aspects of cell activity, researchers have pursued detailed structural analysis of this class of proteins. Because of the complexities in isolating and studying membrane proteins in their native environment, detergents are often employed as a membrane mimetic media. This thesis examines several features of transmembrane (TM) protein structure and folding in detergents through which we are able to gain insights into membrane protein folding, as well as explore the suitability of detergents as membrane-mimetic environments. We first compare the helix-helix association of a series of model TM sequences in a native bilayer to the corresponding association in a detergent environment. We find that while various classes of helix-helix interaction motifs are preserved in detergents, alterations in detergent solvation may, in turn, lead to altered association affinity. We further explore this phenomenon through investigation of the consequences of the insertion of a strongly polar residue into a TM segment. In these studies we find a correlation between sequence-dependent alterations in detergent solvation and predicted in vivo folding. We also extend such analyses to a variety of detergents and native TM segments, finding that native secondary structure, as it occurs in the context of a full-length protein, is generally well preserved in a variety of detergents. Finally, we assess the determinants of membrane protein folding using two-transmembrane segment constructs, in the process optimizing expression, production and characterization techniques for a diverse range of transmembrane protein sequences. Overall this thesis finds that, detergents are capable of solubilizing membrane proteins in a form suitable for in-depth structural characterization that may not be feasible in other environments. Thus, as an approximation of a native membrane, detergents are able to preserve certain features of membrane proteins such as helix-helix association and native secondary structure.
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Detergents as Membrane-mimetic Media for Structural Characterization of Membrane ProteinsTulumello, David 31 August 2012 (has links)
Membrane proteins are essential cellular components, responsible for a wide variety of biological functions. In order to better understand such aspects of cell activity, researchers have pursued detailed structural analysis of this class of proteins. Because of the complexities in isolating and studying membrane proteins in their native environment, detergents are often employed as a membrane mimetic media. This thesis examines several features of transmembrane (TM) protein structure and folding in detergents through which we are able to gain insights into membrane protein folding, as well as explore the suitability of detergents as membrane-mimetic environments. We first compare the helix-helix association of a series of model TM sequences in a native bilayer to the corresponding association in a detergent environment. We find that while various classes of helix-helix interaction motifs are preserved in detergents, alterations in detergent solvation may, in turn, lead to altered association affinity. We further explore this phenomenon through investigation of the consequences of the insertion of a strongly polar residue into a TM segment. In these studies we find a correlation between sequence-dependent alterations in detergent solvation and predicted in vivo folding. We also extend such analyses to a variety of detergents and native TM segments, finding that native secondary structure, as it occurs in the context of a full-length protein, is generally well preserved in a variety of detergents. Finally, we assess the determinants of membrane protein folding using two-transmembrane segment constructs, in the process optimizing expression, production and characterization techniques for a diverse range of transmembrane protein sequences. Overall this thesis finds that, detergents are capable of solubilizing membrane proteins in a form suitable for in-depth structural characterization that may not be feasible in other environments. Thus, as an approximation of a native membrane, detergents are able to preserve certain features of membrane proteins such as helix-helix association and native secondary structure.
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The Interaction Of Consumer Constructed Meanings Of Brand Identity And & / #8216 / designed& / #8217 / ProductOzalp, Yesim 01 June 2005 (has links) (PDF)
This is an attempt to understand the interaction of meanings of brand identity and & / #8216 / designed& / #8217 / product from the consumers& / #8217 / viewpoint. Brand Identity is taken as the & / #8216 / conceived& / #8217 / identity, which overlaps with concepts of brand image and brand associations. & / #8216 / Designed& / #8217 / product is analyzed via dimensions of function, form (aesthetic) and symbol. The aim of the thesis is to find patterns of interaction of functional, emotive and symbolic associations for brand identity and the functional, formal (aesthetic) and symbolic communication of the & / #8216 / designed& / #8217 / product.
A qualitative research paradigm is followed in the thesis, given the emphasis on consumer-constructed meanings. Projective tasks based on dummy models and word associations are used as research tools. The product group included in the study is mobile phones because of high awareness levels and wide interest of the consumers. The context of the interaction is constrained by the nature of product group (fashion and high-tech item) as well as the properties of brands used in the study (Nokia, Motorola and Samsung).
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O jardim em Portugal nos séculos XVII e XVIIILeite, Ana Cristina, 1959- January 1988 (has links)
No description available.
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Cultural Check and Connect Sessions: A Researcher-Designed Pilot Dropout Intervention Program for Ninth Grade African-American StudentsRivers, Angel 21 May 2018 (has links)
The purpose of this mixed-method study, combining a quantitative, quasi-experimental, and qualitative design was to examine a researcher-designed, piloted dropout intervention program that would address the factors that have contributed to African American, ninth-grade “at-risk” students. This phenomenon, also known as the “ninth grade shock” due to the rapid incline within the United States’ traditional public high school setting, has also been a direct connection to the low graduation rates listed for African American students in the state of Georgia. The researcher-designed, dropout intervention program, Cultural Check and Connect Sessions (CC&CS) was evaluated while developing and implementing strategies that will reverse the need for students to drop out while being promoted to the next grade level.
The researcher examined the following variables: Student Perception, Attendance, Discipline, The Number of Failed Courses, and Support Staff Perception. Student data were gathered from the selected students (Group A) using student surveys, staff interviews, and the school’s database, Infinite Campus. Forty African-American students were also selected as a control group (Group B). Both groups of students met the following requirements before the start of the researcher-designed program: 2 or more failed courses on the previous progress report, 3 or more semesters behind from being promoted to the 10th grade, 10 or more unexcused absences, and 3 or more discipline referrals.
When Group A was compared to Group B after the completion of the researcher-designed program, the results of the study revealed that the group was impacted by the researcher-designed, piloted dropout intervention program through the students’ perception of school, attendance, and discipline. This research investigation provides implications and recommendations for all schools educating African American, ninth- grade “at-risk” students in a traditional school learning environment.
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