Applications of thermal processing in pharmaceutical drug product development

Dissertação para obtenção do grau de Mestre no Instituto Superior de Ciências da Saúde Egas Moniz

Functionally partitioned module-based programmable architecture for wireless base-band processing

A specialised reconfigurable architecture is targeted at wireless base-band processing. It is built to cater for multiple wireless standards. It has lower power consumption than the processor-based solution. It can be scaled to run in parallel for processing multiple channels. Test resources are embedded on the architecture and testing strategies are included. This architecture is functionally partitioned according to the common operations found in wireless standards, such as CRC error correction, convolution and interleaving. These modules are linked via Virtual Wire Hardware modules and route-through switch matrices. Data can be processed in any order through this interconnect structure. Virtual Wire ensures the same flexibility as normal interconnects, but the area occupied and the number of switches needed is reduced. The testing algorithm scans all possible paths within the interconnection network exhaustively and searches for faults in the processing modules. The testing algorithm starts by scanning the externally addressable memory space and testing the master controller. The controller then tests every switch in the route-through switch matrix by making loops from the shared memory to each of the switches. The local switch matrix is also tested in the same way. Next the local memory is scanned. Finally, pre-defined test vectors are loaded into local memory to check the processing modules. This paper compares various base-band processing solutions. It describes the proposed platform and its implementation. It outlines the test resources and algorithm. It concludes with the mapping of Bluetooth and GSM base-band onto the platform.

Discovery and characterization of a linear cyclotide from Viola odorata: Implications for the processing of circular proteins

Cyclotides are mini-proteins of 28-37 amino acid residues that have the unusual feature of a head-to-tail cyclic backbone surrounding a cystine knot. This molecular architecture gives the cyclotides heightened resistance to thermal, chemical and enzymatic degradation and has prompted investigations into their use as scaffolds in peptide therapeutics. There are now more than 80 reported cyclotide sequences from plants in the families Rubiaceae, Violaceae and Cucurbitaceae, with a wide variety of biological activities observed. However, potentially limiting the development of cyclotide-based therapeutics is a lack of understanding of the mechanism by which these peptides are cyclized in vivo. Until now, no linear versions of cyclotides have been reported, limiting our understanding of the cyclization mechanism. This study reports the discovery of a naturally occurring linear cyclotide, violacin A, from the plant Viola odorata and discusses the implications for in vivo cyclization of peptides. The elucidation of the cDNA clone of violacin A revealed a point mutation that introduces a stop codon, which inhibits the translation of a key Asn residue that is thought to be required for cyclization. The three-dimensional solution structure of violacin A was determined and found to adopt the cystine knot fold of native cyclotides. Enzymatic stability assays on violacin A indicate that despite an increase in the flexibility of the structure relative to cyclic counterparts, the cystine knot preserves the overall stability of the molecule. (c) 2006 Elsevier Ltd. All rights reserved.

Toward efficient multifeature query processing

In many advanced applications, data are described by multiple high-dimensional features. Moreover, different queries may weight these features differently; some may not even specify all the features. In this paper, we propose our solution to support efficient query processing in these applications. We devise a novel representation that compactly captures f features into two components: The first component is a 2D vector that reflects a distance range ( minimum and maximum values) of the f features with respect to a reference point ( the center of the space) in a metric space and the second component is a bit signature, with two bits per dimension, obtained by analyzing each feature's descending energy histogram. This representation enables two levels of filtering: The first component prunes away points that do not share similar distance ranges, while the bit signature filters away points based on the dimensions of the relevant features. Moreover, the representation facilitates the use of a single index structure to further speed up processing. We employ the classical B+-tree for this purpose. We also propose a KNN search algorithm that exploits the access orders of critical dimensions of highly selective features and partial distances to prune the search space more effectively. Our extensive experiments on both real-life and synthetic data sets show that the proposed solution offers significant performance advantages over sequential scan and retrieval methods using single and multiple VA-files.

Surface k-NN query processing

A k-NN query finds the k nearest-neighbors of a given point from a point database. When it is sufficient to measure object distance using the Euclidian distance, the key to efficient k-NN query processing is to fetch and check the distances of a minimum number of points from the database. For many applications, such as vehicle movement along road networks or rover and animal movement along terrain surfaces, the distance is only meaningful when it is along a valid movement path. For this type of k-NN queries, the focus of efficient query processing is to minimize the cost of computing distances using the environment data (such as the road network data and the terrain data), which can be several orders of magnitude larger than that of the point data. Efficient processing of k-NN queries based on the Euclidian distance or the road network distance has been investigated extensively in the past. In this paper, we investigate the problem of surface k-NN query processing, where the distance is calculated from the shortest path along a terrain surface. This problem is very challenging, as the terrain data can be very large and the computational cost of finding shortest paths is very high. We propose an efficient solution based on multiresolution terrain models. Our approach eliminates the need of costly process of finding shortest paths by ranking objects using estimated lower and upper bounds of distance on multiresolution terrain models.

Distributed processing, reconfigurable processes and active network

The fast spread of the Internet and the increasing demands of the service are leading to radical changes in the structure and management of underlying telecommunications systems. Active networks (ANs) offer the ability to program the network on a per-router, per-user, or even per-packet basis, thus promise greater flexibility than current networks. To make this new network paradigm of active network being widely accepted, a lot of issues need to be solved. Management of the active network is one of the challenges. This thesis investigates an adaptive management solution based on genetic algorithm (GA). The solution uses a distributed GA inspired by bacterium on the active nodes within an active network, to provide adaptive management for the network, especially the service provision problems associated with future network. The thesis also reviews the concepts, theories and technologies associated with the management solution. By exploring the implementation of these active nodes in hardware, this thesis demonstrates the possibility of implementing a GA based adaptive management in the real network that being used today. The concurrent programming language, Handel-C, is used for the description of the design system and a re-configurable computer platform based on a FPGA process element is used for the hardware implementation. The experiment results demonstrate both the availability of the hardware implementation and the efficiency of the proposed management solution.

All-optical processing using cross-phase modulation

The following thesis presents results obtained from both numerical simulation and laboratory experimentation (both of which were carried out by the author). When data is propagated along an optical transmission line some timing irregularities can occur such as timing jitter and phase wander. Traditionally these timing problems would have been corrected by converting the optical signal into the electrical domain and then compensating for the timing irregularity before converting the signal back into the optical domain. However, this thesis posses a potential solution to the problem by remaining completely in the optical domain, eliminating the need for electronics. This is desirable as not only does optical processing reduce the latency effect that their electronic counterpart have, it also holds the possibility of an increase in overall speed. A scheme was proposed which utilises the principle of wavelength conversion to dynamically convert timing irregularities (timing jitter and phase wander) into a change in wavelength (this occurs on a bit-by-bit level and so timing jitter and phase wander can be compensated for simultaneously). This was achieved by optically sampling a linearly chirped, locally generated clock source (the sampling function was achieved using a nonlinear optical loop mirror). The data, now with each bit or code word having a unique wavelength, is then propagated through a dispersion compensation module. The dispersion compensation effectively re-aligns the data in time and so thus, the timing irregularities are removed. The principle of operation was tested using computer simulation before being re-tested in a laboratory environment. A second stage was added to the device to create 3R regeneration. The second stage is used to simply convert the timing suppressed data back into a single wavelength. By controlling the relative timing displacement between stage one and stage two, the wavelength that is finally produced can be controlled.

Rough-terrain groundspeed measurement:a radar-based commercial solution

Off-highway motive plant equipment is costly in capital outlay and maintenance. To reduce these overheads and increase site safety and workrate, a technique of assessing and limiting the velocity of such equipment is required. Due to the extreme environmental conditions met on such sites, conventional velocity measurement techniques are inappropriate. Ogden Electronics Limited were formed specifically to manufacture a motive plant safety system incorporating a speed sensor and sanction unit; to date, the only such commercial unit available. However, problems plague the reliability, accuracy and mass production of this unit. This project assesses the company's exisiting product, and in conjunction with an appreciation of the company history and structure, concludes that this unit is unsuited to its intended application. Means of improving the measurement accuracy and longevity of this unit, commensurate with the company's limited resources and experience, are proposed, both for immediate retrofit and for longer term use. This information is presented in the form of a number of internal reports for the company. The off-highway environment is examined; and in conjunction with an evaluation of means of obtaining a returned signal, comparisons of processing techniques, and on-site gathering of previously unavailable data, preliminary designs for an alternative product are drafted. Theoretical aspects are covered by a literature review of ground-pointing radar, vehicular radar, and velocity measuring systems. This review establishes and collates the body of knowledge in areas previously considered unrelated. Based upon this work, a new design is proposed which is suitable for incorporation into the existing company product range. Following production engineering of the design, five units were constructed, tested and evaluated on-site. After extended field trials, this design has shown itself to possess greater accuracy, reliability and versatility than the existing sensor, at a lower unit cost.

Influence of downstream processing on the breakage of whey protein precipitates

Whey proteins may be fractionated by isoelectric precipitation followed by centrifugal recovery of the precipitate phase. Transport and processing of protein precipitates may alter the precipitate particle properties, which may affect how they behave in subsequent processes. For example, the transport of precipitate solution through pumps, pipes and valves and into a centrifugal separator may cause changes in particle size and density, which may affect the performance of the separator. This work investigates the effect of fluid flow intensity, flow geometry and exposure time on the breakage of whey protein precipitates: Computational fluid dynamics (CFD) was used to quantify the flow intensity in different geometries. Flow geometry can have a critical impact on particle breakage. Sharp geometrical transitions induce large increases in turbulence that can result in substantial particle breakage. As protein precipitate particles break, they tend to form denser more compact structures. The reduction in particle size and increase in compaction is due to breakage. This makes the particles become more resistant to further breakage as particle compactness increases. The effect of flow intensity on particle breakage is coupled to exposure time, with greater exposure time producing more breakage. However, it is expected that the particles will attain an equilibrium particle size and density after prolonged exposure in a constant flow field where no further breakage will occur with exposure time. © 2005 Institution of Chemical Engineers.

Are few-mode fibres a practical solution to the capacity crunch?

In this paper, we compare the nonlinear Shannon capacity of few-mode fibre systems operating with spatial-temporal digital signal processing to the nonlinear Shannon capacity of single-mode fibre systems operating with spectral-temporal digital signal processing. Combining these results with estimates of digital signal processing complexity for each option offers valuable insights to system designers.

Effect of thermal and mechanical processing on tensile properties of powder formed 2124 aluminium and 2124 Al-SiC p metal matrix composite

The aging responses of 2124 Al-SiC p metal matrix composite (MMC) and unreinforced matrix alloy are studied and related to variations in tensile properties. The MMC is aged from Wo starting conditions: (i) stretched and naturally aged and (ii) re-solution treated. Accelerated aging occurs in both MMC conditions compared with unreinforced alloy. Tensile strengths and elastic moduli are improved in the MMC compared with the alloy, but ductility is reduced. Stretched MMC exhibits higher strength but lower ductility and modulus than re-solutioned MMC. The re-solutioned MMC fails by microvoid coalescence in low aging conditions, and by void nucleation and shear in high aging conditions. Failure of the stretched MMC initiates at the surface at specimen shoulders, illustrating the increased notch sensitivity of this condition, and propagates via a zigzag shear fracture mode. Zigzag facet size increases on gross aging. Particle fracture occurs during tensile failure, but also before testing as a result of the manufacturing process. © 1995 The Institute of Materials.

Bottleneck Problem Solution using Biological Models of Attention in High Resolution Tracking Sensors

Every high resolution imaging system suffers from the bottleneck problem. This problem relates to the huge amount of data transmission from the sensor array to a digital signal processing (DSP) and to bottleneck in performance, caused by the requirement to process a large amount of information in parallel. The same problem exists in biological vision systems, where the information, sensed by many millions of receptors should be transmitted and processed in real time. Models, describing the bottleneck problem solutions in biological systems fall in the field of visual attention. This paper presents the bottleneck problem existing in imagers used for real time salient target tracking and proposes a simple solution by employing models of attention, found in biological systems. The bottleneck problem in imaging systems is presented, the existing models of visual attention are discussed and the architecture of the proposed imager is shown.

A Workbench for Document Processing

During the MEMORIAL project time an international consortium has developed a software solution called DDW (Digital Document Workbench). It provides a set of tools to support the process of digitisation of documents from the scanning up to the retrievable presentation of the content. The attention is focused to machine typed archival documents. One of the important features is the evaluation of quality in each step of the process. The workbench consists of automatic parts as well as of parts which request human activity. The measurable improvement of 20% shows the approach is successful.

An Algorithmic Solution for Management of Related Text Objects with Application in Phytopharmacy

This paper presents an algorithmic solution for management of related text objects, in which are integrated algorithms for their extraction from paper or electronic format, for their storage and processing in a relational database. The developed algorithms for data extraction and data analysis enable one to find specific features and relations between the text objects from the database. The algorithmic solution is applied to data from the field of phytopharmacy in Bulgaria. It can be used as a tool and methodology for other subject areas where there are complex relationships between text objects.

Accuracy and optimal sampling in Monte Carlo solution of population balance equations

Implementation of a Monte Carlo simulation for the solution of population balance equations (PBEs) requires choice of initial sample number (N0), number of replicates (M), and number of bins for probability distribution reconstruction (n). It is found that Squared Hellinger Distance, H2, is a useful measurement of the accuracy of Monte Carlo (MC) simulation, and can be related directly to N0, M, and n. Asymptotic approximations of H2 are deduced and tested for both one-dimensional (1-D) and 2-D PBEs with coalescence. The central processing unit (CPU) cost, C, is found in a power-law relationship, C= aMNb0, with the CPU cost index, b, indicating the weighting of N0 in the total CPU cost. n must be chosen to balance accuracy and resolution. For fixed n, M × N0 determines the accuracy of MC prediction; if b > 1, then the optimal solution strategy uses multiple replications and small sample size. Conversely, if 0 < b < 1, one replicate and a large initial sample size is preferred. © 2015 American Institute of Chemical Engineers AIChE J, 61: 2394–2402, 2015