Observation via one-dimensional 13Calpha NMR of local conformational substates in thermal unfolding equilibria of a synthetic analog of the GCN4 leucine zipper.

Synthesis of a 33-residue, capped leucine zipper analogous to that in GCN4 is reported. Histidine and arginine residues are mutated to lysine to reduce the unfolding temperature. CD and ultracentrifugation studies indicate that the molecule is a two-stranded coiled coil under benign conditions. Versions of the same peptide are made with 99% 13Calpha at selected sites. One-dimensional 13C NMR spectra are assigned by inspection and used to study thermal unfolding equilibria over the entire transition from 8 to 73 degrees C. Spectra at the temperature extremes establish the approximate chemical shifts for folded and unfolded forms at each labeled site. Resonances for each amino acid appear at both locations at intermediate T, indicating that folded and unfolded forms interconvert slowly (> >2 ms) on the NMR time scale. Moreover, near room temperature, the structured form's resonance is double at several, but not all, sites, indicating at least two slowly interconverting, structured, local conformational substates. Analysis of the dynamics is possible. For example, near room temperature at the Val-9, Ala-24, and Gly-31 positions, the equilibrium constant for interconversion of the two structured forms is near unity and the time scale is > or= 10-20 ms.

Mathematical analysis of activation thresholds in enzyme-catalyzed positive feedbacks: application to the feedbacks of blood coagulation.

A hierarchy of enzyme-catalyzed positive feedback loops is examined by mathematical and numerical analysis. Four systems are described, from the simplest, in which an enzyme catalyzes its own formation from an inactive precursor, to the most complex, in which two sequential feedback loops act in a cascade. In the latter we also examine the function of a long-range feedback, in which the final enzyme produced in the second loop activates the initial step in the first loop. When the enzymes generated are subject to inhibition or inactivation, all four systems exhibit threshold properties akin to excitable systems like neuron firing. For those that are amenable to mathematical analysis, expressions are derived that relate the excitation threshold to the kinetics of enzyme generation and inhibition and the initial conditions. For the most complex system, it was expedient to employ numerical simulation to demonstrate threshold behavior, and in this case long-range feedback was seen to have two distinct effects. At sufficiently high catalytic rates, this feedback is capable of exciting an otherwise subthreshold system. At lower catalytic rates, where the long-range feedback does not significantly affect the threshold, it nonetheless has a major effect in potentiating the response above the threshold. In particular, oscillatory behavior observed in simulations of sequential feedback loops is abolished when a long-range feedback is present.

Multi-level zero-inflated Poisson regression modelling of correlated count data with excess zeros

Count data with excess zeros relative to a Poisson distribution are common in many biomedical applications. A popular approach to the analysis of such data is to use a zero-inflated Poisson (ZIP) regression model. Often, because of the hierarchical Study design or the data collection procedure, zero-inflation and lack of independence may occur simultaneously, which tender the standard ZIP model inadequate. To account for the preponderance of zero counts and the inherent correlation of observations, a class of multi-level ZIP regression model with random effects is presented. Model fitting is facilitated using an expectation-maximization algorithm, whereas variance components are estimated via residual maximum likelihood estimating equations. A score test for zero-inflation is also presented. The multi-level ZIP model is then generalized to cope with a more complex correlation structure. Application to the analysis of correlated count data from a longitudinal infant feeding study illustrates the usefulness of the approach.

Description and critical appraisal of principal components analysis (PCA) methodology applied to pulsed-field gel electrophoresis profiles of methicillin-resistant Staphylococcus aureus isolates

Principal components analysis (PCA) has been described for over 50 years; however, it is rarely applied to the analysis of epidemiological data. In this study PCA was critically appraised in its ability to reveal relationships between pulsed-field gel electrophoresis (PFGE) profiles of methicillin- resistant Staphylococcus aureus (MRSA) in comparison to the more commonly employed cluster analysis and representation by dendrograms. The PFGE type following SmaI chromosomal digest was determined for 44 multidrug-resistant hospital-acquired methicillin-resistant S. aureus (MR-HA-MRSA) isolates, two multidrug-resistant community-acquired MRSA (MR-CA-MRSA), 50 hospital-acquired MRSA (HA-MRSA) isolates (from the University Hospital Birmingham, NHS Trust, UK) and 34 community-acquired MRSA (CA-MRSA) isolates (from general practitioners in Birmingham, UK). Strain relatedness was determined using Dice band-matching with UPGMA clustering and PCA. The results indicated that PCA revealed relationships between MRSA strains, which were more strongly correlated with known epidemiology, most likely because, unlike cluster analysis, PCA does not have the constraint of generating a hierarchic classification. In addition, PCA provides the opportunity for further analysis to identify key polymorphic bands within complex genotypic profiles, which is not always possible with dendrograms. Here we provide a detailed description of a PCA method for the analysis of PFGE profiles to complement further the epidemiological study of infectious disease. © 2005 Elsevier B.V. All rights reserved.

An introduction to analysis of variance (ANOVA) with special reference to data from clinical experiments in optometry

This article is aimed primarily at eye care practitioners who are undertaking advanced clinical research, and who wish to apply analysis of variance (ANOVA) to their data. ANOVA is a data analysis method of great utility and flexibility. This article describes why and how ANOVA was developed, the basic logic which underlies the method and the assumptions that the method makes for it to be validly applied to data from clinical experiments in optometry. The application of the method to the analysis of a simple data set is then described. In addition, the methods available for making planned comparisons between treatment means and for making post hoc tests are evaluated. The problem of determining the number of replicates or patients required in a given experimental situation is also discussed. Copyright (C) 2000 The College of Optometrists.

Integrated approach to project feasibility analysis:a case study

Feasibility studies of industrial projects consist of multiple analyses carried out sequentially. This is time consuming and each analysis screens out alternatives based solely on the merits of that analysis. In cross-country petroleum pipeline project selection, market analysis determines throughput requirement and supply and demand points. Technical analysis identifies technological options and alternatives for pipe-line routes. Economic and financial analysis derive the least-cost option. The impact assessment addresses environmental issues. The impact assessment often suggests alternative sites, routes, technologies, and/or implementation methodology, necessitating revision of technical and financial analysis. This report suggests an integrated approach to feasibility analysis presented as a case application of a cross-country petroleum pipeline project in India.

Macular pigment optical density is related to blood glutathione levels in healthy individuals

Purpose. To assess the relationship between macular pigment optical density (MPOD) and blood markers for antioxidant defense in otherwise healthy volunteers. Methods. Forty-seven healthy volunteers were subjected to blood analysis to detect the level of circulating glutathione in its reduced (GSH) and oxidized (GSSG) forms. The level of MPOD was measured using heterochromatic flicker photometry. Systemic blood pressure (BP) parameters, heart rate (HR), body mass index (BMI), and plasma levels of total, HDL, and LDL cholesterol and triglycerides (TGs) were also determined. Results. A simple correlation model revealed that the level of MPOD correlated significantly and positively with both GSH (P < 0.001) and t-GSH (P < 0.001) levels but not with those of GSSG (P > 0.05). Age, sex, systemic BP parameters, HR, BMI, and plasma levels of cholesterol and TGs did not have any influence on either MPOD or glutathione levels (all P > 0.05). In addition, a forward stepwise multiple regression analysis showed MPOD to have a significantly and independent correlation with GSH levels (ß = 0.63; P < 0.001). Conclusions. In otherwise healthy older individuals, there is a positive correlation between local and systemic antioxidant defense mechanisms.

Pragmatic approach to the development of robust real-time protocols

This research is concerned with the development of distributed real-time systems, in which software is used for the control of concurrent physical processes. These distributed control systems are required to periodically coordinate the operation of several autonomous physical processes, with the property of an atomic action. The implementation of this coordination must be fault-tolerant if the integrity of the system is to be maintained in the presence of processor or communication failures. Commit protocols have been widely used to provide this type of atomicity and ensure consistency in distributed computer systems. The objective of this research is the development of a class of robust commit protocols, applicable to the coordination of distributed real-time control systems. Extended forms of the standard two phase commit protocol, that provides fault-tolerant and real-time behaviour, were developed. Petri nets are used for the design of the distributed controllers, and to embed the commit protocol models within these controller designs. This composition of controller and protocol model allows the analysis of the complete system in a unified manner. A common problem for Petri net based techniques is that of state space explosion, a modular approach to both the design and analysis would help cope with this problem. Although extensions to Petri nets that allow module construction exist, generally the modularisation is restricted to the specification, and analysis must be performed on the (flat) detailed net. The Petri net designs for the type of distributed systems considered in this research are both large and complex. The top down, bottom up and hybrid synthesis techniques that are used to model large systems in Petri nets are considered. A hybrid approach to Petri net design for a restricted class of communicating processes is developed. Designs produced using this hybrid approach are modular and allow re-use of verified modules. In order to use this form of modular analysis, it is necessary to project an equivalent but reduced behaviour on the modules used. These projections conceal events local to modules that are not essential for the purpose of analysis. To generate the external behaviour, each firing sequence of the subnet is replaced by an atomic transition internal to the module, and the firing of these transitions transforms the input and output markings of the module. Thus local events are concealed through the projection of the external behaviour of modules. This hybrid design approach preserves properties of interest, such as boundedness and liveness, while the systematic concealment of local events allows the management of state space. The approach presented in this research is particularly suited to distributed systems, as the underlying communication model is used as the basis for the interconnection of modules in the design procedure. This hybrid approach is applied to Petri net based design and analysis of distributed controllers for two industrial applications that incorporate the robust, real-time commit protocols developed. Temporal Petri nets, which combine Petri nets and temporal logic, are used to capture and verify causal and temporal aspects of the designs in a unified manner.

A study of magnetic non-linearity and finite length effects in solid iron subjected to a travelling MMF wave

This thesis describes an experimental and analytic study of the effects of magnetic non-linearity and finite length on the loss and field distribution in solid iron due to a travelling mmf wave. In the first half of the thesis, a two-dimensional solution is developed which accounts for the effects of both magnetic non-linearity and eddy-current reaction; this solution is extended, in the second half, to a three-dimensional model. In the two-dimensional solution, new equations for loss and flux/pole are given; these equations contain the primary excitation, the machine parameters and factors describing the shape of the normal B-H curve. The solution applies to machines of any air-gap length. The conditions for maximum loss are defined, and generalised torque/frequency curves are obtained. A relationship between the peripheral component of magnetic field on the surface of the iron and the primary excitation is given. The effects of magnetic non-linearity and finite length are combined analytically by introducing an equivalent constant permeability into a linear three-dimensional analysis. The equivalent constant permeability is defined from the non-linear solution for the two-dimensional magnetic field at the axial centre of the machine to avoid iterative solutions. In the linear three-dimensional analysis, the primary excitation in the passive end-regions of the machine is set equal to zero and the secondary end faces are developed onto the air-gap surface. The analyses, and the assumptions on which they are based, were verified on an experimental machine which consists of a three-phase rotor and alternative solid iron stators, one with copper end rings, and one without copper end rings j the main dimensions of the two stators are identical. Measurements of torque, flux /pole, surface current density and radial power flow were obtained for both stators over a range of frequencies and excitations. Comparison of the measurements on the two stators enabled the individual effects of finite length and saturation to be identified, and the definition of constant equivalent permeability to be verified. The penetration of the peripheral flux into the stator with copper end rings was measured and compared with theoretical penetration curves. Agreement between measured and theoretical results was generally good.

Data analysis methods in optometry Part 4: an introduction to analysis of variance (ANOVA)

In any investigation in optometry involving more that two treatment or patient groups, an investigator should be using ANOVA to analyse the results assuming that the data conform reasonably well to the assumptions of the analysis. Ideally, specific null hypotheses should be built into the experiment from the start so that the treatments variation can be partitioned to test these effects directly. If 'post-hoc' tests are used, then an experimenter should examine the degree of protection offered by the test against the possibilities of making either a type 1 or a type 2 error. All experimenters should be aware of the complexity of ANOVA. The present article describes only one common form of the analysis, viz., that which applies to a single classification of the treatments in a randomised design. There are many different forms of the analysis each of which is appropriate to the analysis of a specific experimental design. The uses of some of the most common forms of ANOVA in optometry have been described in a further article. If in any doubt, an investigator should consult a statistician with experience of the analysis of experiments in optometry since once embarked upon an experiment with an unsuitable design, there may be little that a statistician can do to help.

Analysis of rubber vulcanisates

A study has been made, using High Pressure Liquid Chromatography, of the migration of TMQ (a quinoline type) and 6PPD (a paraphenylenediamine type) antidegradants from a tyre sidewall compound into adjacent casing and liner compounds containing no antidegradant. Migration takes place at a rapid rate, even during the vulcanisation of the composite. After 4000 hours ageing in nitrogen at 100oC, there is a higher level of antidegradants in the casing than in the sidewall. An equilibrium distribution is not obtained. After 114 days at 50oC in 95% relative humidity, the level of solvent extractable 6PPD fell to zero, but subsequent ageing for 2 years in 50 pphm ozone showed no evidence of sidewall cracking. It is suggested that the antidegradant is still active but linked to the polymer chain. An analytical method, for the type and amount of sulphenamide accelerators in vulcanised rubber compounds, has been developed. During the vulcanisation process, the accelerators decay, liberating specific amines which have been solvent extracted, derivatised with 1-chloro-2,4-dinitrobenzene and the yellow coloured zwitter ion analysed using High Pressure Liquid Chromatography. The decay of the accelerator and sulphur during the vulcanisation process, has been studied. It has been demonstrated that the sulphur crosslinking with a styrenebutadiene polymer is a first order reaction, after an initial period during which the accelerator content falls to zero. Variations in sulphur to accelerator ratios gave consistent rate constants for the crosslinking, except for a sulphur level of less than 1% by weight and a ratiio of accelerator to sulphur of 1:1.3. The retention time of the reaction product between sulphur and accelerator from an HPLC column changes with cure time, showing that the precurser to crosslinking is an ever changing material. One of these reaction products has been analysed.

Analysis of organisational climate to improve the adequacy of primary health care in the State of Kuwait

This study covers two areas of contribution to the knowledge, firstly it tried to investigate rigourously the relationships of a number of factors believed that they may affect the climate perception, classified into three types to arrive to prove a hypothesis of the important role that qualification and personal factors play in shaping the climate perception, this is in contrast with situational factors. Secondly, the study tries to recluster the items of a wide-range applied scale for the measurement of climate named HAY in order to overcome the cross-cultural differences between the Kuwaiti and the American society, and to achieve a modified dimensions of climate for a civil service organisation in Kuwait. Furthermore, the study attempts to carry out a diagnostic test for the climate of the Ministry of Public Health in Kuwait, aiming to diagnose the perceived characteristics of the MoPH organisation, and suggests a number of areas to be given attention if an improvement is to be introduced. The study used extensively the statistical and the computer facilities to make the analysis more representing the field data, on the other hand this study is characterised by the very highly responsive rate of the main survey which would affect the findings reliability. Three main field studies are included, the first one was to conduct the main questionnaire where the second was to measure the "should be" climate by the experts of MoPH using the DELPHI technique, and the third was to conduct an extensive meeting with the very top management team in MoPH. Results of the first stage were subject to CLUSTER analysis for the reconstruction of the HAY tool, whereas comparative analysis was carried on between the results of the second and third stages on one side, the first from the other.

Numerical and statistical analysis of long-haul undersea optical communication systems

Firstly, we numerically model a practical 20 Gb/s undersea configuration employing the Return-to-Zero Differential Phase Shift Keying data format. The modelling is completed using the Split-Step Fourier Method to solve the Generalised Nonlinear Schrdinger Equation. We optimise the dispersion map and per-channel launch power of these channels and investigate how the choice of pre/post compensation can influence the performance. After obtaining these optimal configurations, we investigate the Bit Error Rate estimation of these systems and we see that estimation based on Gaussian electrical current systems is appropriate for systems of this type, indicating quasi-linear behaviour. The introduction of narrower pulses due to the deployment of quasi-linear transmission decreases the tolerance to chromatic dispersion and intra-channel nonlinearity. We used tools from Mathematical Statistics to study the behaviour of these channels in order to develop new methods to estimate Bit Error Rate. In the final section, we consider the estimation of Eye Closure Penalty, a popular measure of signal distortion. Using a numerical example and assuming the symmetry of eye closure, we see that we can simply estimate Eye Closure Penalty using Gaussian statistics. We also see that the statistics of the logical ones dominates the statistics of the logical ones dominates the statistics of signal distortion in the case of Return-to-Zero On-Off Keying configurations.

Unified model for performance analysis of IEEE 802.11 ad hoc networks in unsaturated conditions

IEEE 802.11 standard has achieved huge success in the past decade and is still under development to provide higher physical data rate and better quality of service (QoS). An important problem for the development and optimization of IEEE 802.11 networks is the modeling of the MAC layer channel access protocol. Although there are already many theoretic analysis for the 802.11 MAC protocol in the literature, most of the models focus on the saturated traffic and assume infinite buffer at the MAC layer. In this paper we develop a unified analytical model for IEEE 802.11 MAC protocol in ad hoc networks. The impacts of channel access parameters, traffic rate and buffer size at the MAC layer are modeled with the assistance of a generalized Markov chain and an M/G/1/K queue model. The performance of throughput, packet delivery delay and dropping probability can be achieved. Extensive simulations show the analytical model is highly accurate. From the analytical model it is shown that for practical buffer configuration (e.g. buffer size larger than one), we can maximize the total throughput and reduce the packet blocking probability (due to limited buffer size) and the average queuing delay to zero by effectively controlling the offered load. The average MAC layer service delay as well as its standard deviation, is also much lower than that in saturated conditions and has an upper bound. It is also observed that the optimal load is very close to the maximum achievable throughput regardless of the number of stations or buffer size. Moreover, the model is scalable for performance analysis of 802.11e in unsaturated conditions and 802.11 ad hoc networks with heterogenous traffic flows. © 2012 KSI.

Time resolved bit error rate analysis of a fast switching tunable laser for use in optically switched networks

We investigate the use of different direct detection modulation formats in a wavelength switched optical network. We find the minimum time it takes a tunable sampled grating distributed Bragg reflector laser to recover after switching from one wavelength channel to another for different modulation formats. The recovery time is investigated utilizing a field programmable gate array which operates as a time resolved bit error rate detector. The detector offers 93 ps resolution operating at 10.7 Gb/s and allows for all the data received to contribute to the measurement, allowing low bit error rates to be measured at high speed. The recovery times for 10.7 Gb/s non-return-to-zero on–off keyed modulation, 10.7 Gb/s differentially phase shift keyed signal and 21.4 Gb/s differentially quadrature phase shift keyed formats can be as low as 4 ns, 7 ns and 40 ns, respectively. The time resolved phase noise associated with laser settling is simultaneously measured for 21.4 Gb/s differentially quadrature phase shift keyed data and it shows that the phase noise coupled with frequency error is the primary limitation on transmitting immediately after a laser switching event.