TG2, a novel extracellular protein with multiple functions

TG2 is multifunctional enzyme which can be secreted to the cell surface by an unknown mechanism where its Ca(2+)-dependent transamidase activity is implicated in a number of events important to cell behaviour. However, this activity may only be transient due to the oxidation of the enzyme in the extracellular environment including its reaction with NO probably accounting for its many other roles, which are transamidation independent. In this review, we discuss the novel roles of TG2 at the cell surface and in the ECM acting either as a transamidating enzyme or as an extracellular scaffold protein involved in cell adhesion. Such roles include its ability to act as an FN co-receptor for ß integrins or in a heterocomplex with FN interacting with the cell surface heparan sulphate proteoglycan syndecan-4 leading to activation of PKCa. These different properties of TG2 involve this protein in various physiological processes, which if not regulated appropriately can also lead to its involvement in a number of diseases. These include metastatic cancer, tissue fibrosis and coeliac disease, thus increasing its attractiveness as both a therapeutic target and diagnostic marker.

Mathematical modelling of patient risks in a hospital environment, using multiple regression analysis

The aim of this research work was primarily to examine the relevance of patient parameters, ward structures, procedures and practices, in respect of the potential hazards of wound cross-infection and nasal colonisation with multiple resistant strains of Staphylococcus aureus, which it is thought might provide a useful indication of a patient's general susceptibility to wound infection. Information from a large cross-sectional survey involving 12,000 patients from some 41 hospitals and 375 wards was collected over a five-year period from 1967-72, and its validity checked before any subsequent analysis was carried out. Many environmental factors and procedures which had previously been thought (but never conclusively proved) to have an influence on wound infection or nasal colonisation rates, were assessed, and subsequently dismissed as not being significant, provided that the standard of the current range of practices and procedures is maintained and not allowed to deteriorate. Retrospective analysis revealed that the probability of wound infection was influenced by the patient's age, duration of pre-operative hospitalisation, sex, type of wound, presence and type of drain, number of patients in ward, and other special risk factors, whilst nasal colonisation was found to be influenced by the patient's age, total duration of hospitalisation, sex, antibiotics, proportion of occupied beds in the ward, average distance between bed centres and special risk factors. A multi-variate regression analysis technique was used to develop statistical models, consisting of variable patient and environmental factors which were found to have a significant influence on the risks pertaining to wound infection and nasal colonisation. A relationship between wound infection and nasal colonisation was then established and this led to the development of a more advanced model for predicting wound infections, taking advantage of the additional knowledge of the patient's state of nasal colonisation prior to operation.

A quantitative study of the pathological changes in ten patients with multiple system atrophy (MSA)

The densities of the glial cytoplasmic inclusions (GCI), neuronal inclusions (NI), and abnormal neurons were studied in the frontal cortex, hippocampus, cerebellum, basal ganglia and areas of the pons and medulla in 10 cases of multiple system atrophy (MSA). GCI density was greater in the substantia nigra and globus pallidus compared with the frontal cortex and hippocampus. Abnormal neurons were most abundant in the frontal cortex, substantia nigra, and inferior olivary nucleus. NI and abnormal neuron densities were positively correlated in the globus pallidus but negatively correlated in the hippocampus. The NI and GCI were only positively correlated in the pons. GCI in the pons and inferior olivary nucleus, NI in the substantia nigra, and abnormal neurons in the frontal cortex varied significantly between cases. The MSA cases did not cluster according to disease subtype. The data suggest that: 1) the greatest densities of pathological changes occur in the substantia nigra and globus pallidus, 2) density of the GCI is unrelated to that of the NI, and 3) there is overlapping pathology between the various subtypes of MSA.

The performance of stabilized and unstabilized minestone in an aqueous environment with emphasis on its erosion resistance

Britain's sea and flood defences are becoming increasingly aged and as a consequence, more fragile and vulnerable. As the government's philosophy on resources shifts against the use of prime quarried and dredged geo-materials, the need to find alternative bulk materials to bolster Britain's prone defences becomes more pressing. One conceivable source for such a material is colliery waste or minestone. Although a plethora of erosion-abrasion studies have been carried out on soils and soil-cements, very little research has been undertaken to determine the resistance of minestone and its cement stabilized form to the effects of water erosion. The thesis reviews the current extent to which soil-cements, minestone and cement stabilized minestone (CSM) have been employed for hydraulic construction projects. A synopsis is also given on the effects of immersion on shales, mudstones and minestone, especially with regard to the phenomena of slaking. A laboratory study was undertaken featuring a selection of minestones from several British coalfields. The stability of minestone and CSM in sea water and distilled water was assessed using slaking tests and immersion monitoring and the bearing on the use of these materials for hydraulic construction is discussed. Following a review of current erosion apparatus, the erosion/abrasion test and rotating cylinder device were chosen and employed to assess the erosion resistance of minestone and CSM. Comparison was made with a sand mix designed to represent a dredged sand, the more traditional, bulk hydraulic construction material. The results of the erosion study suggest that both minestone and CSM were more resistant to erosion and abrasion than equivalently treated sand mixes. The greater resistance of minestone to the agents of erosion and abrasion is attributed to several factors including the size of the particles, a greater degree of cement bonding and the ability of the minestone aggregate to absorb, rather than transmit shock waves produced by impacting abrasive particles. Although minestone is shown to be highly unstable when subjected to cyclic changes in its moisture content, the study suggests that even in an intertidal regime where cyclic immersion does takes place, minestone will retain sufficient moisture within its fabric to prevent slaking from taking place. The slaking study reveals a close relationship between slaking susceptibility and total pore surface area as revealed by porosimetry. The immersion study shows that although the fabric of CSM is rapidly attacked in sea water, a high degree of the disruption is associated with the edges and corners of samples (ie. free surface) while the integrity of the internal fabric remains relatively intact. CSM samples were shown to be resilient when subjected to immersion in distilled water. An overall assessment of minestone and CSM would suggest that with the implementation of judicious selection and appropriate quality control they could be used as alternative materials for flood and sea defences. It is believed, that even in the harsh regime of a marine environment, CSM could be employed for temporary and sacrificial schemes.

Knowledge elicitation and knowledge representation in a large domain with multiple experts

This paper describes the knowledge elicitation and knowledge representation aspects of a system being developed to help with the design and maintenance of relational data bases. The size algorithmic components. In addition, the domain contains multiple experts, but any given expert's knowledge of this large domain is only partial. The paper discusses the methods and techniques used for knowledge elicitation, which was based on a "broad and shallow" approach at first, moving to a "narrow and deep" one later, and describes the models used for knowledge representation, which were based on a layered "generic and variants" approach. © 1995.

Performance measurement with multiple interrelated variables and threshold target levels:evidence from retail firms in the US

In this study, we developed a DEA-based performance measurement methodology that is consistent with performance assessment frameworks such as the Balanced Scorecard. The methodology developed in this paper takes into account the direct or inverse relationships that may exist among the dimensions of performance to construct appropriate production frontiers. The production frontiers we obtained are deemed appropriate as they consist solely of firms with desirable levels for all dimensions of performance. These levels should be at least equal to the critical values set by decision makers. The properties and advantages of our methodology against competing methodologies are presented through an application to a real-world case study from retail firms operating in the US. A comparative analysis between the new methodology and existing methodologies explains the failure of the existing approaches to define appropriate production frontiers when directly or inversely related dimensions of performance are present and to express the interrelationships between the dimensions of performance.

Correlation between p-GaN growth environment with electrical and optical properties of blue LEDs

Two blue (450 nm) light–emitting diodes (LED), which only differ in top p-GaN layer growth conditions, were comparatively investigated. I-V, C-V, TLM, Electroluminescence (EL) and Photoluminescence (PL) techniques were applied to clarify a correlation between MOCVD carrier gas and internal properties. The A-structure grown in the pure N2 environment demonstrated better parameters than the B-structure grown in the N2/H2 (1:1) gas mixture. The mixed growth atmosphere leaded to an increase of sheet resistances of p-GaN layer. EL and PL measurements confirmed the advantage of the pure N2 utilization, and C(VR) measurement pointed the increase of static charge concentration near the p-GaN interface in the B structure.

Review on protection issues of low-voltage distribution network with multiple powerelectronic-converter-interfaced distribution energy resources

The realisation of an eventual low-voltage (LV) Smart Grid with a complete communication infrastructure is a gradual process. During this evolution the protection scheme of distribution networks should be continuously adapted and optimised to fit the protection and cost requirements at the time. This paper aims to review practices and research around the design of an effective, adaptive and economical distribution network protection scheme. The background of this topic is introduced and potential problems are defined from conventional protection theories and new Smart Grid technologies. Challenges are identified with possible solutions defined as a pathway to the ultimate flexible and reliable LV protection systems.

Performance optimisation of the MAC protocol with multiple contention slots in MIMO ad hoc networks

The multiple-input multiple-output (MIMO) technique can be used to improve the performance of ad hoc networks. Various medium access control (MAC) protocols with multiple contention slots have been proposed to exploit spatial multiplexing for increasing the transport throughput of MIMO ad hoc networks. However, the existence of multiple request-to-send/clear-to-send (RTS/CTS) contention slots represents a severe overhead that limits the improvement on transport throughput achieved by spatial multiplexing. In addition, when the number of contention slots is fixed, the efficiency of RTS/CTS contention is affected by the transmitting power of network nodes. In this study, a joint optimisation scheme on both transmitting power and contention slots number for maximising the transport throughput is presented. This includes the establishment of an analytical model of a simplified MAC protocol with multiple contention slots, the derivation of transport throughput as a function of both transmitting power and the number of contention slots, and the optimisation process based on the transport throughput formula derived. The analytical results obtained, verified by simulation, show that much higher transport throughput can be achieved using the joint optimisation scheme proposed, compared with the non-optimised cases and the results previously reported.

Analysing time series structure with hidden Markov models

This paper consides the problem of extracting the relationships between two time series in a non-linear non-stationary environment with Hidden Markov Models (HMMs). We describe an algorithm which is capable of identifying associations between variables. The method is applied both to synthetic data and real data. We show that HMMs are capable of modelling the oil drilling process and that they outperform existing methods.

Structure and dynamics of multiple cationic vectors-siRNA complexation by all-atomic molecular dynamics simulations

Understanding the molecular mechanism of gene condensation is a key component to rationalizing gene delivery phenomena, including functional properties such as the stability of the gene-vector complex and the intracellular release of the gene. In this work, we adopt an atomistic molecular dynamics simulation approach to study the complexation of short strand duplex RNA with four cationic carrier systems of varying charge and surface topology at different charge ratios. At lower charge ratios, polymers bind quite effectively to siRNA, while at high charge ratios, the complexes are saturated and there are free polymers that are unable to associate with RNA. We also observed reduced fluctuations in RNA structures when complexed with multiple polymers in solution as compared to both free siRNA in water and the single polymer complexes. These novel simulations provide a much better understanding of key mechanistic aspects of gene-polycation complexation and thereby advance progress toward rational design of nonviral gene delivery systems.

Ophthalmological manifestations of multiple sclerosis

Optic neuritis, as a result of the formation of demyelination plaques in the optic nerve, is one of the commonest early symptoms of multiple sclerosis. Hence, it is important that optometrists are aware of the symptoms of optic neuritis and of the conditions with which it can be confused. However, only a proportion of patients with optic neuritis will develop the symptoms of multiple sclerosis. The first part of the article describes the symptoms and differential diagnosis of optic neuritis and its relationship with multiple sclerosis. In the second part of the article, the variety of visual changes and symptoms which can be observed in multiple sclerosis patients will be described.

Protecting agents against malicious host attacks

The introduction of agent technology raises several security issues that are beyond conventional security mechanisms capability and considerations, but research in protecting the agent from malicious host attack is evolving. This research proposes two approaches to protecting an agent from being attacked by a malicious host. The first approach consists of an obfuscation algorithm that is able to protect the confidentiality of an agent and make it more difficult for a malicious host to spy on the agent. The algorithm uses multiple polynomial functions with multiple random inputs to convert an agent's critical data to a value that is meaningless to the malicious host. The effectiveness of the obfuscation algorithm is enhanced by addition of noise code. The second approach consists of a mechanism that is able to protect the integrity of the agent using state information, recorded during the agent execution process in a remote host environment, to detect a manipulation attack by a malicious host. Both approaches are implemented using a master-slave agent architecture that operates on a distributed migration pattern. Two sets of experimental test were conducted. The first set of experiments measures the migration and migration+computation overheads of the itinerary and distributed migration patterns. The second set of experiments is used to measure the security overhead of the proposed approaches. The protection of the agent is assessed by analysis of its effectiveness under known attacks. Finally, an agent-based application, known as Secure Flight Finder Agent-based System (SecureFAS) is developed, in order to prove the function of the proposed approaches.

Evaluation of remote sensing for the detection of landfill gas and leachate in an urban environment

The technique of remote sensing provides a unique view of the earth's surface and considerable areas can be surveyed in a short amount of time. The aim of this project was to evaluate whether remote sensing, particularly using the Airborne Thematic Mapper (ATM) with its wide spectral range, was capable of monitoring landfill sites within an urban environment with the aid of image processing and Geographical Information Systems (GIS) methods. The regions under study were in the West Midlands conurbation and consisted of a large area in what is locally known as the Black Country containing heavy industry intermingled with residential areas, and a large single active landfill in north Birmingham. When waste is collected in large volumes it decays and gives off pollutants. These pollutants, landfill gas and leachate (a liquid effluent), are known to be injurious to vegetation and can cause stress and death. Vegetation under stress can exhibit a physiological change, detectable by the remote sensing systems used. The chemical and biological reactions that create the pollutants are exothermic and the gas and leachate, if they leave the waste, can be warmer than their surroundings. Thermal imagery from the ATM (daylight and dawn) and thermal video were obtained and used to find thermal anomalies on the area under study. The results showed that vegetation stress is not a reliable indicator of landfill gas migration, as sites within an urban environment have a cover too complex for the effects to be identified. Gas emissions from two sites were successfully detected by all the thermal imagery with the thermal ATM being the best. Although the results were somewhat disappointing, recent technical advancements in the remote sensing systems used in this project would allow geo-registration of ATM imagery taken on different occasions and the elimination of the effects of solar insolation.

Increased risk of diabetes mellitus among persons with psychotic symptoms:results from the WHO World Health Survey

OBJECTIVE: To analyze with a symptom-based approach the relationship between psychosis and diabetes mellitus in the general population. METHOD: Nationally representative samples from the World Health Organization (WHO) World Health Survey, totaling 224,743 randomly selected adults 18 years and older from 52 countries worldwide, were interviewed to establish the presence of psychotic symptoms and diabetes mellitus. Presence of psychotic symptoms was established using questions pertaining to positive symptoms from the psychosis screening module of the Composite International Diagnostic Interview. Presence of diabetes was established with a response of "yes" to the question, "Have you ever been diagnosed with diabetes (high blood sugar)?" The World Health Survey was conducted between 2002 and 2004. RESULTS: An increasing number of psychotic symptoms was related to increasing likelihood of diabetes mellitus (OR = 1.27; 95% CI, 1.24-1.30). As compared to no symptoms, at least 1 psychotic symptom substantially elevated the risk (OR = 1.71; 95% CI, 1.61-1.81). In people with a lifetime diagnosis of schizophrenia or psychosis, the prevalence of diabetes was higher in those with current psychotic symptoms (7.3% vs 5.2%; OR = 1.65; 95% CI, 1.21-2.26), suggesting that the persistence of symptoms over time could play a central role. After controlling for different potential confounders, there was a clear increase in the probability of having diabetes as the number of psychotic symptoms increased. The relationship between psychotic symptoms and diabetes was tested with multiple mediation models and path analyses for categorical outcomes. Only body mass index appeared as a relevant mediator in a model with a good fit (ie, χ21 = 3.2, P = .0742; comparative fit index = 0.999). CONCLUSIONS: Psychotic symptoms are related to increased rates of diabetes mellitus in nonclinical samples, independent of several potential confounders-including a clinical diagnosis of psychosis or schizophrenia, previous antipsychotic treatment, depression, lifestyle, and individual or country socioeconomic status. The findings highlight the worldwide relevance of the problem and the importance of identifying the specific paths of this association.