Large-scale production of secreted proteins in Pichia pastoris

The production of recombinant therapeutic proteins is an active area of research in drug development. These bio-therapeutic drugs target nearly 150 disease states and promise to bring better treatments to patients. However, if new bio-therapeutics are to be made more accessible and affordable, improvements in production performance and optimization of processes are necessary. A major challenge lies in controlling the effect of process conditions on production of intact functional proteins. To achieve this, improved tools are needed for bio-processing. For example, implementation of process modeling and high-throughput technologies can be used to achieve quality by design, leading to improvements in productivity. Commercially, the most sought after targets are secreted proteins due to the ease of handling in downstream procedures. This chapter outlines different approaches for production and optimization of secreted proteins in the host Pichia pastoris. © 2012 Springer Science+business Media, LLC.

Large-scale data for multiple-view stereopsis

The seminal multiple-view stereo benchmark evaluations from Middlebury and by Strecha et al. have played a major role in propelling the development of multi-view stereopsis (MVS) methodology. The somewhat small size and variability of these data sets, however, limit their scope and the conclusions that can be derived from them. To facilitate further development within MVS, we here present a new and varied data set consisting of 80 scenes, seen from 49 or 64 accurate camera positions. This is accompanied by accurate structured light scans for reference and evaluation. In addition all images are taken under seven different lighting conditions. As a benchmark and to validate the use of our data set for obtaining reasonable and statistically significant findings about MVS, we have applied the three state-of-the-art MVS algorithms by Campbell et al., Furukawa et al., and Tola et al. to the data set. To do this we have extended the evaluation protocol from the Middlebury evaluation, necessitated by the more complex geometry of some of our scenes. The data set and accompanying evaluation framework are made freely available online. Based on this evaluation, we are able to observe several characteristics of state-of-the-art MVS, e.g. that there is a tradeoff between the quality of the reconstructed 3D points (accuracy) and how much of an object’s surface is captured (completeness). Also, several issues that we hypothesized would challenge MVS, such as specularities and changing lighting conditions did not pose serious problems. Our study finds that the two most pressing issues for MVS are lack of texture and meshing (forming 3D points into closed triangulated surfaces).

Machine learning for large-scale wearable sensor data in Parkinson disease:concepts, promises, pitfalls, and futures

For the treatment and monitoring of Parkinson's disease (PD) to be scientific, a key requirement is that measurement of disease stages and severity is quantitative, reliable, and repeatable. The last 50 years in PD research have been dominated by qualitative, subjective ratings obtained by human interpretation of the presentation of disease signs and symptoms at clinical visits. More recently, “wearable,” sensor-based, quantitative, objective, and easy-to-use systems for quantifying PD signs for large numbers of participants over extended durations have been developed. This technology has the potential to significantly improve both clinical diagnosis and management in PD and the conduct of clinical studies. However, the large-scale, high-dimensional character of the data captured by these wearable sensors requires sophisticated signal processing and machine-learning algorithms to transform it into scientifically and clinically meaningful information. Such algorithms that “learn” from data have shown remarkable success in making accurate predictions for complex problems in which human skill has been required to date, but they are challenging to evaluate and apply without a basic understanding of the underlying logic on which they are based. This article contains a nontechnical tutorial review of relevant machine-learning algorithms, also describing their limitations and how these can be overcome. It discusses implications of this technology and a practical road map for realizing the full potential of this technology in PD research and practice. © 2016 International Parkinson and Movement Disorder Society.

Large scale fabrication of nitrogen vacancy-embedded diamond nanostructures for single-photon source applications

Some color centers in diamond can serve as quantum bits which can be manipulated with microwave pulses and read out with laser, even at room temperature. However, the photon collection efficiency of bulk diamond is greatly reduced by refraction at the diamond/air interface. To address this issue, we fabricated arrays of diamond nanostructures, differing in both diameter and top end shape, with HSQ and Cr as the etching mask materials, aiming toward large scale fabrication of single-photon sources with enhanced collection efficiency made of nitrogen vacancy (NV) embedded diamond. With a mixture of O2 and CHF3 gas plasma, diamond pillars with diameters down to 45 nm were obtained. The top end shape evolution has been represented with a simple model. The tests of size dependent single-photon properties confirmed an improved single-photon collection efficiency enhancement, larger than tenfold, and a mild decrease of decoherence time with decreasing pillar diameter was observed as expected. These results provide useful information for future applications of nanostructured diamond as a single-photon source.

A comparison of two distributed large-volume measurement systems:the mobile spatial co-ordinate measuring system and the indoor global positioning system

Advances in the area of industrial metrology have generated new technologies that are capable of measuring components with complex geometry and large dimensions. However, no standard or best-practice guides are available for the majority of such systems. Therefore, these new systems require appropriate testing and verification in order for the users to understand their full potential prior to their deployment in a real manufacturing environment. This is a crucial stage, especially when more than one system can be used for a specific measurement task. In this paper, two relatively new large-volume measurement systems, the mobile spatial co-ordinate measuring system (MScMS) and the indoor global positioning system (iGPS), are reviewed. These two systems utilize different technologies: the MScMS is based on ultrasound and radiofrequency signal transmission and the iGPS uses laser technology. Both systems have components with small dimensions that are distributed around the measuring area to form a network of sensors allowing rapid dimensional measurements to be performed in relation to large-size objects, with typical dimensions of several decametres. The portability, reconfigurability, and ease of installation make these systems attractive for many industries that manufacture large-scale products. In this paper, the major technical aspects of the two systems are briefly described and compared. Initial results of the tests performed to establish the repeatability and reproducibility of these systems are also presented. © IMechE 2009.

Risk based decision support system for effective implementation of projects

Conventional project management techniques are not always sufficient to ensure time, cost and quality achievement of large-scale construction projects due to complexity in planning, design and implementation processes. The main reasons for project non-achievement are changes in scope and design, changes in government policies and regulations, unforeseen inflation, underestimation and improper estimation. Projects that are exposed to such an uncertain environment can be effectively managed with the application of risk management throughout the project's life cycle. However, the effectiveness of risk management depends on the technique through which the effects of risk factors are analysed/quantified. This study proposes the Analytic Hierarchy Process (AHP), a multiple attribute decision making technique, as a tool for risk analysis because it can handle subjective as well as objective factors in a decision model that are conflicting in nature. This provides a decision support system (DSS) to project management for making the right decision at the right time for ensuring project success in line with organisation policy, project objectives and a competitive business environment. The whole methodology is explained through a case application of a cross-country petroleum pipeline project in India and its effectiveness in project management is demonstrated.

Design, modeling and construction of a novel ablative fast pyrolysis reactor and product collection system

The objective of this work was to design, construct and commission a new ablative pyrolysis reactor and a high efficiency product collection system. The reactor was to have a nominal throughput of 10 kg/11r of dry biomass and be inherently scalable up to an industrial scale application of 10 tones/hr. The whole process consists of a bladed ablative pyrolysis reactor, two high efficiency cyclones for char removal and a disk and doughnut quench column combined with a wet walled electrostatic precipitator, which is directly mounted on top, for liquids collection. In order to aid design and scale-up calculations, detailed mathematical modelling was undertaken of the reaction system enabling sizes, efficiencies and operating conditions to be determined. Specifically, a modular approach was taken due to the iterative nature of some of the design methodologies, with the output from one module being the input to the next. Separate modules were developed for the determination of the biomass ablation rate, specification of the reactor capacity, cyclone design, quench column design and electrostatic precipitator design. These models enabled a rigorous design protocol to be developed capable of specifying the required reactor and product collection system size for specified biomass throughputs, operating conditions and collection efficiencies. The reactor proved capable of generating an ablation rate of 0.63 mm/s for pine wood at a temperature of 525 'DC with a relative velocity between the heated surface and reacting biomass particle of 12.1 m/s. The reactor achieved a maximum throughput of 2.3 kg/hr, which was the maximum the biomass feeder could supply. The reactor is capable of being operated at a far higher throughput but this would require a new feeder and drive motor to be purchased. Modelling showed that the reactor is capable of achieving a reactor throughput of approximately 30 kg/hr. This is an area that should be considered for the future as the reactor is currently operating well below its theoretical maximum. Calculations show that the current product collection system could operate efficiently up to a maximum feed rate of 10 kg/Fir, provided the inert gas supply was adjusted accordingly to keep the vapour residence time in the electrostatic precipitator above one second. Operation above 10 kg/hr would require some modifications to the product collection system. Eight experimental runs were documented and considered successful, more were attempted but due to equipment failure had to be abandoned. This does not detract from the fact that the reactor and product collection system design was extremely efficient. The maximum total liquid yield was 64.9 % liquid yields on a dry wood fed basis. It is considered that the liquid yield would have been higher had there been sufficient development time to overcome certain operational difficulties and if longer operating runs had been attempted to offset product losses occurring due to the difficulties in collecting all available product from a large scale collection unit. The liquids collection system was highly efficient and modeling determined a liquid collection efficiency of above 99% on a mass basis. This was validated due to the fact that a dry ice/acetone condenser and a cotton wool filter downstream of the collection unit enabled mass measurements of the amount of condensable product exiting the product collection unit. This showed that the collection efficiency was in excess of 99% on a mass basis.

The development of a multi-function computer-assisted instruction system using a hierarchical database structure as the lesson compendium.

Computer-Based Learning systems of one sort or another have been in existence for almost 20 years, but they have yet to achieve real credibility within Commerce, Industry or Education. A variety of reasons could be postulated for this, typically: - cost - complexity - inefficiency - inflexibility - tedium Obviously different systems deserve different levels and types of criticism, but it still remains true that Computer-Based Learning (CBL) is falling significantly short of its potential. Experience of a small, but highly successful CBL system within a large, geographically distributed industry (the National Coal Board) prompted an investigation into currently available packages, the original intention being to purchase the most suitable software and run it on existing computer hardware, alongside existing software systems. It became apparent that none of the available CBL packages were suitable, and a decision was taken to develop an in-house Computer-Assisted Instruction system according to the following criteria: - cheap to run; - easy to author course material; - easy to use; - requires no computing knowledge to use (as either an author or student) ; - efficient in the use of computer resources; - has a comprehensive range of facilities at all levels. This thesis describes the initial investigation, resultant observations and the design, development and implementation of the SCHOOL system. One of the principal characteristics c£ SCHOOL is that it uses a hierarchical database structure for the storage of course material - thereby providing inherently a great deal of the power, flexibility and efficiency originally required. Trials using the SCHOOL system on IBM 303X series equipment are also detailed, along with proposed and current development work on what is essentially an operational CBL system within a large-scale Industrial environment.

Designing a methodology for an office communication and information system:for executives in the Malaysian public sector : the Prime Minister's office

Modern managers are under tremendous pressure in attempting to fulfil a profoundly complex managerial task, that of handling information resources. Information management, an intricate process requiring a high measure of human cognition and discernment, involves matching a manager's lack of information processing capacity against his information needs, with voluminous information at his disposal. The nature of the task will undoubtedly become more complex in the case of a large organisation. Management of large-scale organisations is therefore an exceedingly challenging prospect for any manager to be faced with. A system that supports executive information needs will help reduce managerial and informational mismatches. In the context of the Malaysian public sector, the task of overall management lies with the Prime Minister and the Cabinet. The Prime Minister's Office is presently supporting the Prime Minister's information and managerial needs, although not without various shortcomings. The rigid formalised structure predominant of the Malaysian public sector, so opposed to dynamic treatment of problematic issues as faced by that sector, further escalates the managerial and organisational problem of coping with a state of complexity. The principal features of the research are twofold: the development of a methodology for diagnosing the problem organisation' and the design of an office system. The methodological development is done in the context of the Malaysian public sector, and aims at understanding the complexity of its communication and control situation. The outcome is a viable model of the public sector. `Design', on the other hand, is developing a syntax or language for office systems which provides an alternative to current views on office systems. The design is done with reference to, rather than for, the Prime Minister's Office. The desirable outcome will be an office model called Office Communication and Information System (OCIS).

High accuracy mobile robot positioning using external large volume metrology instruments

A method of accurately controlling the position of a mobile robot using an external large volume metrology (LVM) instrument is presented in this article. By utilising an LVM instrument such as a laser tracker or indoor GPS (iGPS) in mobile robot navigation, many of the most difficult problems in mobile robot navigation can be simplified or avoided. Using the real-time position information from the laser tracker, a very simple navigation algorithm, and a low cost robot, 5mm repeatability was achieved over a volume of 30m radius. A surface digitisation scan of a wind turbine blade section was also demonstrated, illustrating possible applications of the method for manufacturing processes. Further, iGPS guidance of a small KUKA omni-directional robot has been demonstrated, and a full scale prototype system is being developed in cooperation with KUKA Robotics, UK. © 2011 Taylor & Francis.

Optical fibre limits:an approach using ASE channel estimation

In this talk we investigate the usage of spectrally shaped amplified spontaneous emission (ASE) in order to emulate highly dispersed wavelength division multiplexed (WDM) signals in an optical transmission system. Such a technique offers various simplifications to large scale WDM experiments. Not only does it offer a reduction in transmitter complexity, removing the need for multiple source lasers, it potentially reduces the test and measurement complexity by requiring only the centre channel of a WDM system to be measured in order to estimate WDM worst case performance. The use of ASE as a test and measurement tool is well established in optical communication systems and several measurement techniques will be discussed [1, 2]. One of the most prevalent uses of ASE is in the measurement of receiver sensitivity where ASE is introduced in order to degrade the optical signal to noise ratio (OSNR) and measure the resulting bit error rate (BER) at the receiver. From an analytical point of view noise has been used to emulate system performance, the Gaussian Noise model is used as an estimate of highly dispersed signals and has had consider- able interest [3]. The work to be presented here extends the use of ASE by using it as a metric to emulate highly dispersed WDM signals and in the process reduce WDM transmitter complexity and receiver measurement time in a lab environment. Results thus far have indicated [2] that such a transmitter configuration is consistent with an AWGN model for transmission, with modulation format complexity and nonlinearities playing a key role in estimating the performance of systems utilising the ASE channel emulation technique. We conclude this work by investigating techniques capable of characterising the nonlinear and damage limits of optical fibres and the resultant information capacity limits. REFERENCES McCarthy, M. E., N. Mac Suibhne, S. T. Le, P. Harper, and A. D. Ellis, “High spectral efficiency transmission emulation for non-linear transmission performance estimation for high order modulation formats," 2014 European Conference on IEEE Optical Communication (ECOC), 2014. 2. Ellis, A., N. Mac Suibhne, F. Gunning, and S. Sygletos, “Expressions for the nonlinear trans- mission performance of multi-mode optical fiber," Opt. Express, Vol. 21, 22834{22846, 2013. Vacondio, F., O. Rival, C. Simonneau, E. Grellier, A. Bononi, L. Lorcy, J. Antona, and S. Bigo, “On nonlinear distortions of highly dispersive optical coherent systems," Opt. Express, Vol. 20, 1022-1032, 2012.

Permanent magnet synchronous generator based wind power generation system fault protection schemes

The PMSG-based wind power generation system protection is presented in this paper. For large-scale systems, a voltagesource converter rectifier is included. Protection circuits for this topology are studied with simulation results for cable permanent fault conditions. These electrical protection methods are all in terms of dumping redundant energy resulting from disrupted path of power delivery. Pitch control of large-scale wind turbines are considered for effectively reducing rotor shaft overspeed. Detailed analysis and calculation of damping power and resistances are presented. Simulation results including fault overcurrent, DC-link overvoltage and wind turbine overspeed are shown to illustrate the system responses under different protection schemes to compare their application and effectiveness.

Large volume metrology process model:measurability analysis with integration of metrology classification model and feature-based selection model

Aircraft manufacturing industries are looking for solutions in order to increase their productivity. One of the solutions is to apply the metrology systems during the production and assembly processes. Metrology Process Model (MPM) (Maropoulos et al, 2007) has been introduced which emphasises metrology applications with assembly planning, manufacturing processes and product designing. Measurability analysis is part of the MPM and the aim of this analysis is to check the feasibility for measuring the designed large scale components. Measurability Analysis has been integrated in order to provide an efficient matching system. Metrology database is structured by developing the Metrology Classification Model. Furthermore, the feature-based selection model is also explained. By combining two classification models, a novel approach and selection processes for integrated measurability analysis system (MAS) are introduced and such integrated MAS could provide much more meaningful matching results for the operators. © Springer-Verlag Berlin Heidelberg 2010.