Crystallizing RNA has been an imperative facet and a challenging task in the world of RNA research. Assistive methods such as Chaperone Assisted RNA Crystallography (CARC), employing monoclonal antibody fragments (Fabs) as crystallization chaperones have enabled us to obtain RNA crystal structures by increasing the crystal contacts and providing initial phasing information. Using this technology the crystal structure of [delta]C209 P4-P6 RNA (an independent folding domain of the self-splicing Tetrahymena group I intron) complexed to Fab2 (high affinity binding Fab) has been resolved to 1.95 Å (1). Although the complexed class I ligase ribozyme has also been crystallized using CARC (2), in practice, it has been found that the crystallization of, large RNA-Fab complex remains a confrontation. The possible reason for this difficulty is that Fabs have not been optimized for crystallization when complexed with RNA. Here we have used the Surface Entropy Reduction technique (SER) for the optimization process. Candidate residues for mutations were identified based on combining results from visual inspection of [delta]C209 P4-P6/Fab2 crystal structure complex using pyMOL software and a web-based SER software. The protruding lysine and glutamate residues were mutated to a set of alanine (Super Mutant Alanine SMA) and serine (Super Mutant Serine SMS) mutant clones. Filter binding assay studies confirmed that the mutant clones bind to [delta]C209 P4-P6 with similar binding affinities as that of the parent Fab2. Large scale expression of the mutants, parent clone and [delta]C209 P4-P6 RNA were optimised. Crystal trays for [delta]C209 P4-P6 complexed with Fab2, Fab2SMA and Fab2SMS were set-up side-by-side using Hampton crystal screen kits and ~600 conditions including temperature as a variable condition were screened. Crystal screening shows significantly higher crystal-forming ratios for the mutant complexes. As the chosen SER residues are far away from the CDR regions of the Fab, the same set of mutations can be potentially applied to other Fabs binding to a variety of ribozymes and riboswitches to improve the crystallizability of the Fab-RNA complex.

Photolithography is the most complex of the operations involved in the fabrication of a wafer, and it requires the greatest precision. Photolithography is used to create multiple layers of circuit patterns on a chip. Traditionally, wafer fab operations, and in particular, those performed in the photolithography processing area, have always presented challenging scheduling and control problems. Some of the characteristics that make the photolithography processing area difficult to schedule are as follows: reentrant flow, unpredictable yield and rework time at critical operations, shared resources such as reticles, rapidly changing technologies, and lot dedication for steppers and scanners for critical layers. This processing area, where wafers are exposed using scanners or steppers, typically, comprises the bottleneck workstations. Also, the numbers of reticles available for a given layer of product type are limited. Consequently, it is important to develop appropriate schedules to ensure effective utilization of the tools involved. In this study, a manufacturing line that is used to produce four dynamic random access memory (DRAM) products, requiring approximately 240 stages with 18 photolithography layers, is considered. The problem we propose to investigate can concisely be described as follows: Given a set of products to be processed in a photolithography area consisting of steppers and scanners (tools), with each product requiring a specific reticle type, determine the sequence in which to process the lots on the tools loaded with requisite reticles, so as to minimize the cycle time. The reticles required for processing a product are known apriori and can be transferred from one tool to another. Also, the lot dedication requirement has to be met. This requirement pertains to the fact that some of the layers of a lot should be processed on the same tool. (Scanner or Stepper). The processing of other layers may not require lot dedication. These are handled accordingly. Some lots may enter into the system with the requirement of processing them urgently. (called hot lots). These are handled in the formulation of the problem as such. Two solution methodologies are presented for the above stated problem. The first methodology uses a mathematical programming based approach. For the given routes and processing times of the product types, the entire problem is formulated as an Integer program. This integer program uses the start time of the jobs at various operations and the availability of reticles as variables, among others. The objective is to reduce the cycle time of the lots released into the system. The cycle time of a lot is defined as the time that a lot spends in the system. Results from the experimentation for integer program show that the computation time for solving small size problems is very high. A methodology is presented to solve this model efficiently. The second methodology consists of the development of a new dispatching rule for scheduling lots in the photolithography processing area. This along with the other dispatching rules discussed in the literature are implemented using the Autosched AP software to study the impact that lot dedication makes on the performance of a fab. The performance measures that are considered include throughput, cycle time, WIP and utilization of tool sets. The results are presented for 1-level, 2-level and 3-level lot dedication schemes. . It is shown that the 3- level lot dedication scheme performs the best under no preventive maintenance/breakdown case while, for the deterministic value of unscheduled breakdown times and preventive maintenance schedule used, 1-level lot dedication performed the best. Even though the 3-level lot dedication scheme is more flexible as compared to the 1–level lot dedication scheme, yet for the values of unscheduled breakdown times and preventive maintenance schedule used, the performance of the 3- level lot dedication scheme is worse than that of the 1- level lot dedication scheme. For another set of break down time values and preventive maintenance schedule, the outcome can be different. We also compare the performance of the proposed procedure with that of the dispatching rules available with the AutoSched AP software. The results indicate that the proposed procedure is consistent in generating better solutions under different operating conditions. / Master of Science

The semiconductor industry provides a host of very challenging problems in production planning and scheduling because of the unique features of the wafer fab. This research addresses the need to develop an approach, which can be used to generate optimal or near-optimal solutions to the scheduling problem of a wafer fab, by using Mathematical Programming for a general case of a wafer fab. The problem is approached in two steps. First, the number of lots of different products to be released into the system during each planning period is determined, such that the total tardiness of the product orders is minimized over the planning horizon. Second, the schedule of these lots is determined so that the cycle time of each lot released into the system is minimized. Thus, the performance measures based both on due dates and cycle time are considered. The lot release, tardiness problem is formulated as an integer linear program, and a 3-phase procedure, which utilizes a variation of the Wilkerson-Irwin algorithm, is developed. The performance of this 3-phase procedure is further improved by using insights from classical scheduling theory. The scheduling problem is formulated as a 0-1 integer linear program. An algorithm is developed for tightening the LP relaxation of this 0-1 integer linear programming model (of the scheduling problem) leading to a better performance of the branch and bound procedure used for its solution. Lagrangian relaxation is applied on a carefully chosen set of constraints in the scheduling problem, and a Lagrangian heuristic is developed for scheduling the jobs in each period of the planning horizon. Several useful insights are developed throughout to further improve the performance of the proposed algorithm. Experiments are conducted for both the tardiness and the scheduling problems. Five experiments are conducted for the tardiness problem. Each experiment has a different combination of number of products, machines, and work orders in a small sized wafer fab (2 to 6 products, 8 to 10 station families, 15 to 30 workstations, 9 to19 work orders, and 100 to 250 lots per work order). The solutions obtained by the 3-phase procedure are compared to the optimal solutions of the corresponding tardiness problems, and the tardiness per work order for the 3-phase procedure is 0% to 25% greater than the optimal solution. But the time required to obtain the optimal solution is 22 to 1074 times greater than the time required to obtain the solution through the 3-phase procedure. Thus, the 3-phase procedure can generate almost optimal solutions and requires much smaller computation time than that required by the optimal solution. Four experiments are conducted to test the performance of the scheduling problem. Each experiment has a different combination of number of products, machines, routes, bottleneck stations, processing times, and product mix entering the system each day in a small sized wafer fab (2 products, 8 station families, 18 workstations, and 8 to 10 lots released per day into the system). The solution quality of the schedule generated by the Lagrangian heuristic is compared to the solution provided by the standard dispatching rules available in practice. In each experiment, the cycle time of a product for each dispatching rule is divided by the best cycle time for that product over all the dispatching rules in that experiment. This ratio for the Lagrangian heuristic in each experiment and over all the experiments varies from 100% to 104%. For the standard dispatching rules, this ratio ranges from 100% to 120% in each experiment and also over all the experiments. The average of the ratio over all the experiments is the least for the Lagrangian heuristic. This indicates that for the experiments conducted, the Lagrangian heuristic consistently provides a solution that is, or is close to, the best solution and, hence, quite competitive when compared to the standard dispatching rules. / Master of Science

No description available.

BIM står för Building Information Modeling. Det är en ny teknik för att konstruera en virtuell modell av en byggnad i digitalt format. De stora fördelarna med BIM är att alla komponenter som läggs till i modellen innehåller information. Av informationen genereras automatiskt de handlingar och listor som behövs. Dessutom fås presentationsmaterial i form av 3D-modeller utan något extra arbete. Undersökningen behandlar ett företag och varför de inte genomfört en övergång från 2D-CAD till BIM och syftet är därför att visa dem vilka effektiviseringsmöjligheter som finns.

This report reviews the field of bispecific antibodies, artificially engineered antibodies thathave the ability to bind two or more different antigen simultaneously. Historical as well asrecently developed techniques are demonstrated, together with formats in preclinical andclinical development. We studied the field with the future needs of the developers in mind,when it comes to the processes and tools that can be offered by GE Healthcare BiosciencesAB. The development of bispecific antibodies gave rise to new challenges and product-relatedimpurities, which are handled by various methods. We argue for, based on the formats inclinical and preclinical development, that the methods already used to purify monospecificantibodies remain the most successful methods for the purification of bispecific antibodies.This, together with the design strategies that resolve the initial bottle-necks, ensures that theneeds of the developers are met to the same extent as for monoclonal antibodies. The methodsand formats demonstrated here do not represent all that are available or under trial.

Made available in DSpace on 2015-04-14T13:20:32Z (GMT). No. of bitstreams: 1 446978.pdf: 1507542 bytes, checksum: 9248757bf7ace288dbc4a9f2b4c28e5e (MD5) Previous issue date: 2013-01-29 / This thesis proposes to analyze how the consumer society has contributed to the economic vulnerability of users of Social Service of Aeronautics Garrison of Porto Alegre (GUARNAE-PA), under the V Regional Air Command, aiming to contribute to the development of educational actions with the objective of reflection on the theme of consumption. For both following specific objectives were delimited: to investigate how the situation of economic vulnerability presents itself as demand for Social Service of GUARNAE-PA; to identify what are the socio-demographic characteristics(gender, age, income, institutional affiliation, educational level) of users in vulnerable economic situation assisted by Social Service; to know if the structure of the COMAER's Social Assistance System enables the Social Service of GUARNAE-PA coping with situations arising from the economic vulnerability of its users and to identify if the actions developed by Social Service of GUARNAE-PA has contributed to cope with this situations. Economic vulnerability understood from the perspective of indebtedness and over-indebtedness. To walk the path of this research we opted for the use of qualitative and quantitative approaches, with emphasis on the first one. The results show that consumption plays the leading role in the lives of research subjects and are associated with the satisfaction of needs, welfare, comfort and status it represents. In this context, we highlight the role of advertising and credit expansion as motivators in the process of borrowing and indebtedness. / A presente disserta??o prop?e-se a analisar de que forma a sociedade de consumo tem contribu?do para a vulnerabilidade econ?mica dos usu?rios do Servi?o Social, da Guarni??o de Aeron?utica de Porto Alegre, no ?mbito do V Comando A?reo Regional, objetivando contribuir para o desenvolvimento de a??es educativas que visem ? reflex?o acerca da tem?tica do consumo. Para tanto se delimitou os seguintes objetivos espec?ficos: investigar como a situa??o de vulnerabilidade econ?mica se apresenta enquanto demanda para o Servi?o Social da GUARNAEPA; identificar quais s?o as caracter?sticas sociodemogr?ficas (g?nero, idade, renda, v?nculo institucional, n?vel educacional) dos usu?rios em situa??o de vulnerabilidade econ?mica, atendidos pelo Servi?o Social; conhecer se a estrutura do Sistema de Assist?ncia Social do COMAER viabiliza ao Servi?o Social da GUARNAE-PA o enfrentamento das situa??es decorrentes da vulnerabilidade econ?mica dos seus usu?rios; e identificar como as transforma??es no mundo do consumo influenciam nas situa??es de vulnerabilidade econ?mica dos usu?rios do Servi?o Social; vulnerabilidade econ?mica entendida sob a ?tica do endividamento e do superendividamento. Para percorrer o caminho da pesquisa, optou-se pela utiliza??o das abordagens qualitativa e quantitativa, com ?nfase na primeira. Os resultados apontam que o consumo ocupa um lugar central na vida dos sujeitos da pesquisa e est? associado ? satisfa??o de necessidades, bem-estar, conforto e o status que ele representa. Nesse contexto, destaca-se o papel da publicidade e a expans?o do cr?dito como motivadores do processo de endividamento e superendividamento.

Cette thèse porte sur l'élaboration d'un vecteur particulaire lipidique reconnaissant activement<br />les tissus cérébraux après son administration par voie intraveineuse. Ce système devrait favoriser l'accumulation au sein du cerveau, de molécules thérapeutiques dans le cadre du traitement des maladies cérébrales comme les gliomes malins. La première partie de notre travail consistait à greffer sur la surface de nanocapsules lipidiques (LNC) des anticorps<br />monoclonaux d'origine murine (OX26) ou des fragments Fab' dirigés contre le récepteur à la transferrine de rat, surexprimé sur l'endothélium cérébral. Des immunonanocapsules portant entre 16 et 183 anticorps entiers et entre 42 et 173 fragments Fab' ont été obtenues. Leur capacité à s'associer aux cellules endothéliales cérébrales de rat a ensuite été vérifiée. De<br />plus, 24 h après leur administration chez le rat, la concentration dans le cerveau des OX26-<br />immunonanocapsules et des Fab'-immunonanocapsules était respectivement 2 et 1,5 fois plus<br />élevée que celle des LNC dépourvues de ligands.

PCM test structures are commonly used to check the produced wafers from the standpoint of the technologist. In general these structures are managed inside the FAB and are focused on standard device properties. Hence their development and analysis is not driven by analog circuit blocks, which are sensitive or often used. Especially for DFM/Y of analog circuits the correlation between design and technology has to be defined. The knowledge of electrical behavior of test structures helps to improve the designer's sensitivity to technological questions. This paper presents a method to bring the PCM methodology into the analog circuit design to improve design performance, yield estimation and technology correlation. We show how both analog circuit and PCM blocks can be simulated and analyzed in the design phase.

Class of 2015 Abstract / Objectives: To determine the incidence of late coagulopathy and characterize those requiring antivenom retreatment among rattlesnake envenomation patients managed by the Arizona Poison and Drug Information Center (APDIC). Methods: This descriptive, retrospective chart review used data extracted from APDIC charts. Data included coagulopathy lab values recorded during treatment, vials of antivenom required to achieve initial control, total vials during therapy, incidence of initial coagulopathy, use of extended infusion, time until treatment, and permanent sequelae due to snakebite. Demographic information was also recorded. Late coagulopathy is defined as coagulopathy occurring after completion of maintenance dosing, and can be considered recurrent or delayed. Delayed coagulopathy occurs in the absence of an initial coagulopathy, while recurrent coagulopathy requires an initial event previously controlled by antivenom therapy. Results: Of 321 identified reports, 120 patients were treated with antivenom, had outpatient follow-up, and were included in analysis. Sixty-one (50.8%) patients did not have an initial coagulopathy, while 59 (49.2%) had an initial coagulopathy. Late coagulopathy occurred in 63 (52.5%) of patients. Delayed coagulopathies occurred in 19 (31.1%) of patients with no initial coagulopathy; Of those with an initial coagulopathy, recurrent coagulopathies occurred in 44 (74.5%) of patients. Patients with initial coagulopathy were statistically more likely to develop a late coagulopathy than those with no initial coagulopathy (p<0.001). Seventeen patients required retreatment post-discharge. Conclusions: Patients envenomated by rattlesnakes are at high risk for developing late coagulopathies. Close outpatient follow-up is imperative for monitoring of coagulopathies. Need for retreatment with FabAV post-discharge is not uncommon.