Purification of complex biopharmaceuticals with new processes, advanced analytics and computer-aided process design tools

Dissertação para obtenção do Grau de Mestre em Biotecnologia

Computer aided process planning (CAPP) for flat rolling of copper alloys

The manufacture of copper alloy flat rolled metals involves hot and cold rolling operations, together with annealing and other secondary processes, to transform castings (mainly slabs and cakes) into such shapes as strip, plate, sheet, etc. Production is mainly to customer orders in a wide range of specifications for dimensions and properties. However, order quantities are often small and so process planning plays an important role in this industry. Much research work has been done in the past in relation to the technology of flat rolling and the details of the operations, however, there is little or no evidence of any research in the planning of processes for this type of manufacture. Practical observation in a number of rolling mills has established the type of manual process planning traditionally used in this industry. This manual approach, however, has inherent drawbacks, being particularly dependent on the individual planners who gain their knowledge over a long span of practical experience. The introduction of the retrieval CAPP approach to this industry was a first step to reduce these problems. But this could not provide a long-term answer because of the need for an experienced planner to supervise generation of any plan. It also fails to take account of the dynamic nature of the parameters involved in the planning, such as the availability of resources, operation conditions and variations in the costs. The other alternative is the use of a generative approach to planning in the rolling mill context. In this thesis, generative methods are developed for the selection of optimal routes for single orders and then for batches of orders, bearing in mind equipment restrictions, production costs and material yield. The batch order process planning involves the use of a special cluster analysis algorithm for optimal grouping of the orders. This research concentrates on cold-rolling operations. A prototype model of the proposed CAPP system, including both single order and batch order planning options, has been developed and tested on real order data in the industry. The results were satisfactory and compared very favourably with the existing manual and retrieval methods.

Intelligent System for Computer Aided Assembly Process Planning

This paper presents the concepts of the intelligent system for aiding of the module assembly technology. The first part of this paper presents a project of intelligent support system for computer aided assembly process planning. The second part includes a coincidence description of the chosen aspects of implementation of this intelligent system using technologies of artificial intelligence (artificial neural networks, fuzzy logic, expert systems and genetic algorithms).

Supporting content-based image retrieval and computer-aided diagnosis systems with association rule-based techniques

In this work, we take advantage of association rule mining to support two types of medical systems: the Content-based Image Retrieval (CBIR) systems and the Computer-Aided Diagnosis (CAD) systems. For content-based retrieval, association rules are employed to reduce the dimensionality of the feature vectors that represent the images and to improve the precision of the similarity queries. We refer to the association rule-based method to improve CBIR systems proposed here as Feature selection through Association Rules (FAR). To improve CAD systems, we propose the Image Diagnosis Enhancement through Association rules (IDEA) method. Association rules are employed to suggest a second opinion to the radiologist or a preliminary diagnosis of a new image. A second opinion automatically obtained can either accelerate the process of diagnosing or to strengthen a hypothesis, increasing the probability of a prescribed treatment be successful. Two new algorithms are proposed to support the IDEA method: to pre-process low-level features and to propose a preliminary diagnosis based on association rules. We performed several experiments to validate the proposed methods. The results indicate that association rules can be successfully applied to improve CBIR and CAD systems, empowering the arsenal of techniques to support medical image analysis in medical systems. (C) 2009 Elsevier B.V. All rights reserved.

Computer-aided recognition of dental implants in X-ray images

Dental implant recognition in patients without available records is a time-consuming and not straightforward task. The traditional method is a complete user-dependent process, where the expert compares a 2D X-ray image of the dental implant with a generic database. Due to the high number of implants available and the similarity between them, automatic/semi-automatic frameworks to aide implant model detection are essential. In this study, a novel computer-aided framework for dental implant recognition is suggested. The proposed method relies on image processing concepts, namely: (i) a segmentation strategy for semi-automatic implant delineation; and (ii) a machine learning approach for implant model recognition. Although the segmentation technique is the main focus of the current study, preliminary details of the machine learning approach are also reported. Two different scenarios are used to validate the framework: (1) comparison of the semi-automatic contours against implant’s manual contours of 125 X-ray images; and (2) classification of 11 known implants using a large reference database of 601 implants. Regarding experiment 1, 0.97±0.01, 2.24±0.85 pixels and 11.12±6 pixels of dice metric, mean absolute distance and Hausdorff distance were obtained, respectively. In experiment 2, 91% of the implants were successfully recognized while reducing the reference database to 5% of its original size. Overall, the segmentation technique achieved accurate implant contours. Although the preliminary classification results prove the concept of the current work, more features and an extended database should be used in a future work.

Computer-aided volume measurement of posttraumatic orbits reconstructed with AO titanium mesh plates: accuracy and reliability

PURPOSE: To prospectively evaluate the accuracy and reliability of "freehand" posttraumatic orbital wall reconstruction with AO (Arbeitsgemeinschaft Osteosynthese) titanium mesh plates by using computer-aided volumetric measurement of the bony orbits. METHODS: Bony orbital volume was measured in 12 patients from coronal CT scan slices using OsiriX Medical Image software. After defining the volumetric limits of the orbit, the segmentation of the bony orbital region of interest of each single slice was performed. At the end of the segmentation process, all regions of interest were grouped and the volume was computed. The same procedure was performed on both orbits, and thereafter the volume of the contralateral uninjured orbit was used as a control for comparison. RESULTS: In all patients, the volume data of the reconstructed orbit fitted that of the contralateral uninjured orbit with accuracy to within 1.85 cm3 (7%). CONCLUSIONS: This preliminary study has demonstrated that posttraumatic orbital wall reconstruction using "freehand" bending and placement of AO titanium mesh plates results in a high success rate in re-establishing preoperative bony volume, which closely approximates that of the contralateral uninjured orbit.

In vitro precision of fit of computer-aided designed and computer-aided manufactured titanium screw-retained fixed dental prostheses before and after ceramic veneering

OBJECTIVE To compare the precision of fit of full-arch implant-supported screw-retained computer-aided designed and computer-aided manufactured (CAD/CAM) titanium-fixed dental prostheses (FDP) before and after veneering. The null-hypothesis was that there is no difference in vertical microgap values between pure titanium frameworks and FDPs after porcelain firing. MATERIALS AND METHODS Five CAD/CAM titanium grade IV frameworks for a screw-retained 10-unit implant-supported reconstruction on six implants (FDI tooth positions 15, 13, 11, 21, 23, 25) were fabricated after digitizing the implant platforms and the cuspid-supporting framework resin pattern with a laser scanner (CARES(®) Scan CS2; Institut Straumann AG, Basel, Switzerland). A bonder, an opaquer, three layers of porcelain, and one layer of glaze were applied (Vita Titankeramik) and fired according to the manufacturer's preheating and fire cycle instructions at 400-800°C. The one-screw test (implant 25 screw-retained) was applied before and after veneering of the FDPs to assess the vertical microgap between implant and framework platform with a scanning electron microscope. The mean microgap was calculated from interproximal and buccal values. Statistical comparison was performed with non-parametric tests. RESULTS All vertical microgaps were clinically acceptable with values <90 μm. No statistically significant pairwise difference (P = 0.98) was observed between the relative effects of vertical microgap of unveneered (median 19 μm; 95% CI 13-35 μm) and veneered FDPs (20 μm; 13-31 μm), providing support for the null-hypothesis. Analysis within the groups showed significantly different values between the five implants of the FDPs before (P = 0.044) and after veneering (P = 0.020), while a monotonous trend of increasing values from implant 23 (closest position to screw-retained implant 25) to 15 (most distant implant) could not be observed (P = 0.169, P = 0.270). CONCLUSIONS Full-arch CAD/CAM titanium screw-retained frameworks have a high accuracy. Porcelain firing procedure had no impact on the precision of fit of the final FDPs. All implant microgap measurements of each FDP showed clinically acceptable vertical misfit values before and after veneering. Thus, the results do not only show accurate performance of the milling and firing but show also a reproducible scanning and designing process.

Computer aided design and manufacture for three dimensional milling

Advances in both computer technology and the necessary mathematical models capable of capturing the geometry of arbitarily shaped objects has led to the development in this thesis of a surface generation package called 'IBSCURF' aimed at providing a more economically viable solution to free-form surface manufacture. A suit of computer programs written in FORTRAN 77 has been developed to provide computer aids for every aspect of work in designing and machining free-form surfaces. A vector-valued parametric method was used for shape description and a lofting technique employed for the construction of the surface. The development of the package 'IBSCURF' consists of two phases. The first deals with CAD. The design process commences in defining the cross-sections which are represented by uniform B-spline curves as approximations to give polygons. The order of the curve and the position and number of the polygon vertices can be used as parameters for the modification to achieve the required curves. When the definitions of the sectional curves is complete, the surface is interpolated over them by cubic cardinal splines. To use the CAD function of the package to design a mould for a plastic handle, a mathematical model was developed. To facilitate the integration of design and machining using the mathematical representation of the surface, the second phase of the package is concerned with CAM which enables the generation of tool offset positions for ball-nosed cutters and a general post-processor has been developed which automatically generates NC tape programs for any CNC milling machine. The two phases of these programs have been successfully implemented, as a CAD/CAM package for free-form surfaces on the VAX 11/750 super-minicomputer with graphics facilities for displaying drawings interactively on the terminal screen. The development of this package has been beneficial in all aspects of design and machining of free form surfaces.

Computer aided form roll design

Cold roll forming is an extremely important but little studied sheet metal forming process. In this thesis, the process of cold roll forming is introduced and it is seen that form roll design is central to the cold roll forming process. The conventional design and manufacture of form rolls is discussed and it is observed that surrounding the design process are a number of activities which although peripheral are time consuming and a possible source of error. A CAD/CAM system is described which alleviates many of the problems traditional to form roll design. New techniques for the calculation of strip length and controlling the means of forming bends are detailed. The CAD/CAM system's advantages and limitations are discussed and, whilst the system has numerous significant advantages, its principal limitation can be said to be the need to manufacture form rolls and test them on a mill before a design can be stated satisfactory. A survey of the previous theoretical and experimental analysis of cold roll forming is presented and is found to be limited. By considering the previous work, a method of numerical analysis of the cold roll forming process is proposed based on a minimum energy approach. Parallel to the numerical analysis, a comprehensive range of software has been developed to enhance the designer's visualisation of the effects of his form roll design. A complementary approach to the analysis of form roll design is the generation of form roll design, a method for the partial generation of designs is described. It is suggested that the two approaches should continue in parallel and that the limitation of each approach is knowledge of the cold roll forming process. Hence, an initial experimental investigation of the rolling of channel sections is described. Finally, areas of potential future work are discussed.

Computer aided design and manufacture of form-rolls

Cold roll forming of thin-walled sections is a very useful process in the sheet metal industry. However, the conventional method for the design and manufacture of form-rolls, the special tooling used in the cold roll forming process, is a very time consuming and skill demanding exercise. This thesis describes the establishment of a stand-alone minicomputer based CAD/CAM system for assisting the design and manufacture of form-rolls. The work was undertaken in collaboration with a leading manufacturer of thin-walled sections. A package of computer programs have been developed to provide computer aids for every aspect of work in form-roll design and manufacture. The programs have been successfully implemented, as an integrated CAD/CAM software system, on the ICL PERQ minicomputer with graphics facilities. Thus, the developed CAD/CAM system is a single-user workstation, with software facilities to help the user to perform the conventional roll design activities including the design of the finished section, the flower pattern, and the form-rolls. A roll editor program can then be used to modify, if required, the computer generated roll profiles. As far as manufacturing is concerned, a special-purpose roll machining program and postprocessor can be used in conjunction to generate the NC control part-programs for the production of form-rolls by NC turning. Graphics facilities have been incorporated into the CAD/CAM software programs to display drawings interactively on the computer screen throughout all stages of execution of the CAD/CAM software. It has been found that computerisation can shorten the lead time in all activities dealing with the design and manufacture of form-rolls, and small or medium size manufacturing companies can gain benefits from the CAD/CM! technology by developing, according to its own specification, a tailor-made CAD/CAM software system on a low cost minicomputer.

The Use of Situation Representation when Searching for Solutions in Computer Aided Design Systems

Projects solutions reuse methodology is offered for software development. The main idea consists in connection of the system objective with the situation using the entities which describe the condition of the system in the process of the objective statement. Every situation is associated with one or several design solutions, which can be used at the development. Based on this connection the situation representing language has been created, it lets to express a problem situation using a natural language describe. The similarity measure has been built to compare situations, it is based on the similarity coefficients with adding the absent part weight.

Computer-aided tool for the teaching of relational algebra in data base courses

This article describes the design and implementation of computer-aided tool called Relational Algebra Translator (RAT) in data base courses, for the teaching of relational algebra. There was a problem when introducing the relational algebra topic in the course EIF 211 Design and Implementation of Databases, which belongs to the career of Engineering in Information Systems of the National University of Costa Rica, because students attending this course were lacking profound mathematical knowledge, which led to a learning problem, being this an important subject to understand what the data bases search and request do RAT comes along to enhance the teaching-learning process.It introduces the architectural and design principles required for its implementation, such as: the language symbol table, the gramatical rules and the basic algorithms that RAT uses to translate from relational algebra to SQL language. This tool has been used for one periods and has demonstrated to be effective in the learning-teaching process.  This urged investigators to publish it in the web site: www.slinfo.una.ac.cr in order for this tool to be used in other university courses.

Using Computer-aided Drug Design and Medicinal Chemistry Strategies in the Fight Against Diabetes

The aim of this work is to present a simple, practical and efficient protocol for drug design, in particular Diabetes, which includes selection of the illness, good choice of a target as well as a bioactive ligand and then usage of various computer aided drug design and medicinal chemistry tools to design novel potential drug candidates in different diseases. We have selected the validated target dipeptidyl peptidase IV (DPP-IV), whose inhibition contributes to reduce glucose levels in type 2 diabetes patients. The most active inhibitor with complex X-ray structure reported was initially extracted from the BindingDB database. By using molecular modification strategies widely used in medicinal chemistry, besides current state-of-the-art tools in drug design (including flexible docking, virtual screening, molecular interaction fields, molecular dynamics. ADME and toxicity predictions), we have proposed 4 novel potential DPP-IV inhibitors with drug properties for Diabetes control, which have been supported and validated by all the computational tools used herewith.

Computer-aided Drug Design of Novel PLA(2) Inhibitor Candidates for Treatment of Snakebite

Phospholipases A(2) (PLA(2)) are enzymes commonly found in snake venoms from Viperidae and Elaphidae families, which are major components thereof. Many plants are used in traditional medicine its active agents against various effects induced by snakebite. This article presents the PLA(2) BthTX-I structure prediction based on homology modeling. In addition, we have performed virtual screening in a large database yielding a set of potential bioactive inhibitors. A flexible docking program was used to investigate the interactions between the receptor and the new ligands. We have performed molecular interaction fields (MIFs) calculations with the phospholipase model. Results confirm the important role of Lys49 for binding ligands and suggest three additional residues as well. We have proposed a theoretically nontoxic, drug-like, and potential novel BthTX-I inhibitor. These calculations have been used to guide the design of novel phospholipase inhibitors as potential lead compounds that may be optimized for future treatment of snakebite victims as well as other human diseases in which PLA(2) enzymes are involved.