Mechanism of protein catobolism in skeletal muscle during cancer cachexia

Cancer cachexia is characterised by selective depletion of skeletal muscle protein reserves. The ubiquitin-proteasome proteolytic pathway has been shown to be responsible for muscle wasting in a range of cachectic conditions including cancer cachexia. To establish the importance of this pathway in muscle wasting during cancer (and sepsis), a quantitative competitive RT-PCR (QcRT-PCR) method was developed to measure the mRNA levels of the proteasome sub units C2a and C5ß and the ubiquitin-conjugating enzyme E214k. Western blotting was also used to measure the 20S proteasome and E214k protein expression. In vivo studies in mice bearing a cachexia inducing murine colon adenocarcinoma (MAC16) demonstrated the effect of progressive weight loss on the mRNA and protein expression for 20S proteasome subunits, as well as the ubiquitin-conjugating enzyme, E214k, in gastrocnemius and pectoral muscles. QcRT-PCR measurements showed a good correlation between expression of the proteasome subunits (C2 and CS) and the E214k enzyme mRNA and weight loss in gastrocnemius muscle, where expression increased with increasing weight loss followed by a decrease in expression at higher weight losses (25-27%). Similar results were obtained in pectoral muscles, but with the expression being several fold lower in comparison to that in gastrocnemius muscle, reflecting the different degrees of protein degradation in the two muscles during the process of cancer cachexia. Western blot analysis of 20S and E214k protein expression followed a similar pattern with respect to weight loss as that found with mRNA. In addition, mRNA and protein expression of the 20S proteasome subunits and E214k enzyme was measured in biopsies from cachectic cancer patients, which also showed a good correlation between weight loss and proteasome expression, demonstrating a progressive increase in expression of the proteasome subunits and E214k mRNA and protein in cachectic patients with progressively increasing weight loss.The effect of the cachexia-inducing tumour product PIF (proteolysis inducing factor) and 15-hydroxyeicosatetraenoic acid (15-HETE), the arachidoinic acid metabolite (thought to be the intracellular transducer of PIF action) has also been determined. Using a surrogate model system for skeletal muscle, C2C12 myotubes in vitro, it was shown that both PIF and 15-HETE increased proteasome subunit expression (C2a and C5ß) as well as the E214k enzyme. This increase gene expression was attenuated by preincubation with EPA or the 15-lipoxygenase inhibitor CV-6504; immunoblotting also confirmed these findings. Similarly, in sepsis-induced cachexia in NMRI mice there was increased mRNA and protein expression of the 20S proteasome subunits and the E214k enzyme, which was inhibited by EPA treatment. These results suggest that 15-HETE is the intracellular mediator for PIF induced protein degradation in skeletal muscle, and that elevated muscle catabolism is accomplished through upregulation of the ubiquitin-proteasome-proteolytic pathway. Furthermore, both EPA and CV -6504 have shown anti-cachectic properties, which could be used in the future for the treatment of cancer cachexia and other similar catabolic conditions.

KEMNAD:a knowledge engineering methodology for negotiating agent development

Automated negotiation is widely applied in various domains. However, the development of such systems is a complex knowledge and software engineering task. So, a methodology there will be helpful. Unfortunately, none of existing methodologies can offer sufficient, detailed support for such system development. To remove this limitation, this paper develops a new methodology made up of: (1) a generic framework (architectural pattern) for the main task, and (2) a library of modular and reusable design pattern (templates) of subtasks. Thus, it is much easier to build a negotiating agent by assembling these standardised components rather than reinventing the wheel each time. Moreover, since these patterns are identified from a wide variety of existing negotiating agents (especially high impact ones), they can also improve the quality of the final systems developed. In addition, our methodology reveals what types of domain knowledge need to be input into the negotiating agents. This in turn provides a basis for developing techniques to acquire the domain knowledge from human users. This is important because negotiation agents act faithfully on the behalf of their human users and thus the relevant domain knowledge must be acquired from the human users. Finally, our methodology is validated with one high impact system.

OntoPedigree:modelling pedigrees for traceability in supply chains

The sharing of product and process information plays a central role in coordinating supply chains operations and is a key driver for their success. "Linked pedigrees" - linked datasets, that encapsulate event based traceability information of artifacts as they move along the supply chain, provide a scalable mechanism to record and facilitate the sharing of track and trace knowledge among supply chain partners. In this paper we present "OntoPedigree" a content ontology design pattern for the representation of linked pedigrees, that can be specialised and extended to define domain specific traceability ontologies. Events captured within the pedigrees are specified using EPCIS - a GS1 standard for the specification of traceability information within and across enterprises, while certification information is described using PROV - a vocabulary for modelling provenance of resources. We exemplify the utility of OntoPedigree in linked pedigrees generated for supply chains within the perishable goods and pharmaceuticals sectors.

Microstructured polymer optical fibre sensors for opto-acoustic endoscopy

Opto-acoustic imaging is a growing field of research in recent years, providing functional imaging of physiological biomarkers, such as the oxygenation of haemoglobin. Piezo electric transducers are the industry standard detector for ultrasonics, but their limited bandwidth, susceptibility to electromagnetic interference and their inversely proportional sensitivity to size all affect the detector performance. Sensors based on polymer optical fibres (POF) are immune to electromagnetic interference, have lower acoustic impedance and a reduced Young's Modulus compared to silica fibres. Furthermore, POF enables the possibility of a wideband sensor and a size appropriate to endoscopy. Micro-structured POF (mPOF) used in an interferometric detector has been shown to be an order of magnitude more sensitive than silica fibre at 1 MHz and 3 times more sensitive at 10 MHz. We present the first opto-acoustic measurements obtained using a 4.7mm PMMA mPOF Bragg grating with a fibre diameter of 130 μm and present the lateral directivity pattern of a PMMA mPOF FBG ultrasound sensor over a frequency range of 1-50 MHz. We discuss the impact of the pattern with respect to the targeted application and draw conclusions on how to mitigate the problems encountered.

Combining analytic hierarchy process and goal programming for logistics distribution network design

Logistics distribution network design is one of the major decision problems arising in contemporary supply chain management. The decision involves many quantitative and qualitative factors that may be conflicting in nature. This paper applies an integrated multiple criteria decision making approach to design an optimal distribution network. In the approach, the analytic hierarchy process (AHP) is used first to determine the relative importance weightings or priorities of alternative warehouses with respect to both deliverer oriented and customer oriented criteria. Then, the goal programming (GP) model incorporating the constraints of system, resource, and AHP priority is formulated to select the best set of warehouses without exceeding the limited available resources. In this paper, two commercial packages are used: Expert Choice for determining the AHP priorities of the warehouses, and LINDO for solving the GP model. © 2007 IEEE.

Spray drier simulation and air flow pattern studies

The literature pertaining to the key stages of spray drying has been reviewed in the context of the mathematical modelling of drier performance. A critical review is also presented of previous spray drying models. A new mathematical model has been developed for prediction of spray drier performance. This is applicable to slurries of rigid, porous crust-forming materials to predict trajectories and drying profiles for droplets with a distribution of sizes sprayed from a centrifugal pressure nozzle. The model has been validated by comparing model predictions to experimental data from a pilot-scale counter-current drier and from a full-scale co-current drier. For the latter, the computed product moisture content was within 2%, and the computed air exit temperature within 10oC of experimental data. Air flow patterns have been investigated in a 1.2m diameter transparent countercurrent spray tower by flow visualisation. Smoke was introduced into various zones within the tower to trace the direction, and gauge the intensity, of the air flow. By means of a set of variable-angle air inlet nozzles, a variety of air entry configurations was investigated. The existence of a core of high rotational and axial velocity channelling up the axis of the tower was confirmed. The stability of flow within the core was found to be strongly dependent upon the air entry arrangement. A probe was developed for the measurement of air temperature and humidity profiles. This was employed for studying evaporation of pure water drops in a 1.2m diameter pilot-scale counter-current drier. A rapid approach to the exit air properties was detected within a 1m distance from the air entry ports. Measured radial profiles were found to be virtually flat but, from the axial profiles, the existence of plug-flow, well-mixed-flow and some degree of air short-circuiting can be inferred. The model and conclusions should assist in the improved design and optimum operation of industrial spray driers.

Some aspects of system design for production management in the rolling-mill industry

Case studies in copper-alloy rolling mill companies showed that existing planning systems suffer from numerous shortcomings. Where computerised systems are in use, these tend to simply emulate older manual systems and still rely heavily on modification by experienced planners on the shopfloor. As the size and number of orders increase, the task of process planners, while seeking to optimise the manufacturing objectives and keep within the production constraints, becomes extremely complicated because of the number of options for mixing or splitting the orders into batches. This thesis develops a modular approach to computerisation of the production management and planning functions. The full functional specification of each module is discussed, together with practical problems associated with their phased implementation. By adapting the Distributed Bill of Material concept from Material Requirements Planning (MRP) philosophy, the production routes generated by the planning system are broken down to identify the rolling stages required. Then to optimise the use of material at each rolling stage, the system generates an optimal cutting pattern using a new algorithm that produces practical solutions to the cutting stock problem. It is shown that the proposed system can be accommodated on a micro-computer, which brings it into the reach of typical companies in the copper-alloy rolling industry, where profit margins are traditionally low and the cost of widespread use of mainframe computers would be prohibitive.

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.

Hierarchical case-based reasoning to support knitwear design

Knitwear design is a creative activity that is hard to automate using the computer. The production of the associated knitting pattern, however, is repetitive, time-consuming and error-prone, calling for automation. Our objectives are two-fold: to facilitate the design and to ease the burden of calculations and checks in pattern production. We conduct a feasibility study for applying case-based reasoning in knitwear design: we describe appropriate methods and show their application.

Topographic studies of scalp potentials evoked by pattern presentation

The waveform and scalp distribution of the visual evoked potentials elicited by stimuli in the foveal and parafoveal regions have been investigated in a group of normal humans using a 16-channel `brain mapping' system. The waveform and topography of the responses to pattern onset and pattern reversal stimulation were investigated, using 4 x 4o full field and 4 x 2o lateral and altitudinal half-field stimuli. The responses were composed of several successive peaks which are in some respects consistent with those demonstrated by other workers using larger field sizes. The differences in the behaviour of these components with respect to the position of the stimulus in the visual field were suggestive of origins in different areas of the visual cortex and/or different visual mechanism. Of particular interest were the major early positive components `P90' and `P95' of the responses to pattern onset and pattern reversal stimulation respectively. More detailed exploration of the behaviour of these major early positive components was carried out using `M-scaled' stimuli selected to activate one square centimetre patches of striate cortex and associated extrastriate re-projections, positioned at different points in the foveal and parafoveal area of the visual field. The inter- and intra-subject variability in amplitude and localisation of the signals elicited by these targets was considered to be a reflection of the individual variations in relationship of visual field projections with the pattern of gyri and fissures on the proximal surface of the occipital lobe. The behaviour of component P90 of the onset response is consistent with a lateral origin in extrastriate visual cortex; that of P95 of the pattern reversal response is consistent in some respects with a striate cortical origin, but in others with a partial origin in extrastriate cortex.

Multi-criteria logistics distribution network design using SAS/OR

This paper explores the use of the optimization procedures in SAS/OR software with application to the contemporary logistics distribution network design using an integrated multiple criteria decision making approach. Unlike the traditional optimization techniques, the proposed approach, combining analytic hierarchy process (AHP) and goal programming (GP), considers both quantitative and qualitative factors. In the integrated approach, AHP is used to determine the relative importance weightings or priorities of alternative warehouses with respect to both deliverer oriented and customer oriented criteria. Then, a GP model incorporating the constraints of system, resource, and AHP priority is formulated to select the best set of warehouses without exceeding the limited available resources. To facilitate the use of integrated multiple criteria decision making approach by SAS users, an ORMCDM code was implemented in the SAS programming language. The SAS macro developed in this paper selects the chosen variables from a SAS data file and constructs sets of linear programming models based on the selected GP model. An example is given to illustrate how one could use the code to design the logistics distribution network.

Design optimization of short-stroke single-phase tubular permanent-magnet motor for refrigeration applications

This paper describes a design methodology to achieve optimal performance for a short-stroke single-phase tubular permanent-magnet motor which drives a reciprocating vapor compressor. The steady-state characteristic of the direct-drive linear-motor compressor system is analyzed, an analytical formula for predicting iron loss is presented, and a motor-design procedure which takes into account the effect of compressor loads under nominal operating condition is formulated. It is shown that the motor efficiency can be optimized with respect to two leading dimensional ratios. Experimental results validate the proposed design methodology. Copyright © 2010 IEEE.

Characteristics of motor resonance predict the pattern of flash-lag effects for biological motion

Background - When a moving stimulus and a briefly flashed static stimulus are physically aligned in space the static stimulus is perceived as lagging behind the moving stimulus. This vastly replicated phenomenon is known as the Flash-Lag Effect (FLE). For the first time we employed biological motion as the moving stimulus, which is important for two reasons. Firstly, biological motion is processed by visual as well as somatosensory brain areas, which makes it a prime candidate for elucidating the interplay between the two systems with respect to the FLE. Secondly, discussions about the mechanisms of the FLE tend to recur to evolutionary arguments, while most studies employ highly artificial stimuli with constant velocities. Methodology/Principal Finding - Since biological motion is ecologically valid it follows complex patterns with changing velocity. We therefore compared biological to symbolic motion with the same acceleration profile. Our results with 16 observers revealed a qualitatively different pattern for biological compared to symbolic motion and this pattern was predicted by the characteristics of motor resonance: The amount of anticipatory processing of perceived actions based on the induced perspective and agency modulated the FLE. Conclusions/Significance - Our study provides first evidence for an FLE with non-linear motion in general and with biological motion in particular. Our results suggest that predictive coding within the sensorimotor system alone cannot explain the FLE. Our findings are compatible with visual prediction (Nijhawan, 2008) which assumes that extrapolated motion representations within the visual system generate the FLE. These representations are modulated by sudden visual input (e.g. offset signals) or by input from other systems (e.g. sensorimotor) that can boost or attenuate overshooting representations in accordance with biased neural competition (Desimone & Duncan, 1995).

Exposing market mechanism design trade-offs via multi-objective evolutionary search

Market mechanisms are a means by which resources in contention can be allocated between contending parties, both in human economies and those populated by software agents. Designing such mechanisms has traditionally been carried out by hand, and more recently by automation. Assessing these mechanisms typically involves them being evaluated with respect to multiple conflicting objectives, which can often be nonlinear, noisy, and expensive to compute. For typical performance objectives, it is known that designed mechanisms often fall short on being optimal across all objectives simultaneously. However, in all previous automated approaches, either only a single objective is considered, or else the multiple performance objectives are combined into a single objective. In this paper we do not aggregate objectives, instead considering a direct, novel application of multi-objective evolutionary algorithms (MOEAs) to the problem of automated mechanism design. This allows the automatic discovery of trade-offs that such objectives impose on mechanisms. We pose the problem of mechanism design, specifically for the class of linear redistribution mechanisms, as a naturally existing multi-objective optimisation problem. We apply a modified version of NSGA-II in order to design mechanisms within this class, given economically relevant objectives such as welfare and fairness. This application of NSGA-II exposes tradeoffs between objectives, revealing relationships between them that were otherwise unknown for this mechanism class. The understanding of the trade-off gained from the application of MOEAs can thus help practitioners with an insightful application of discovered mechanisms in their respective real/artificial markets.

The handbook of engineering self-aware and self-expressive systems

When faced with the task of designing and implementing a new self-aware and self-expressive computing system, researchers and practitioners need a set of guidelines on how to use the concepts and foundations developed in the Engineering Proprioception in Computing Systems (EPiCS) project. This report provides such guidelines on how to design self-aware and self-expressive computing systems in a principled way. We have documented different categories of self-awareness and self-expression level using architectural patterns. We have also documented common architectural primitives, their possible candidate techniques and attributes for architecting self-aware and self-expressive systems. Drawing on the knowledge obtained from the previous investigations, we proposed a pattern driven methodology for engineering self-aware and self-expressive systems to assist in utilising the patterns and primitives during design. The methodology contains detailed guidance to make decisions with respect to the possible design alternatives, providing a systematic way to build self-aware and self-expressive systems. Then, we qualitatively and quantitatively evaluated the methodology using two case studies. The results reveal that our pattern driven methodology covers the main aspects of engineering self-aware and self-expressive systems, and that the resulted systems perform significantly better than the non-self-aware systems.