Long-range and high-precision correlation optical time-domain reflectometry utilizing an all-fiber chaotic source

We propose a long range, high precision optical time domain reflectometry (OTDR) based on an all-fiber supercontinuum source. The source simply consists of a CW pump laser with moderate power and a section of fiber, which has a zero dispersion wavelength near the laser's central wavelength. Spectrum and time domain properties of the source are investigated, showing that the source has great capability in nonlinear optics, such as correlation OTDR due to its ultra-wide-band chaotic behavior, and mm-scale spatial resolution is demonstrated. Then we analyze the key factors limiting the operational range of such an OTDR, e. g., integral Rayleigh backscattering and the fiber loss, which degrades the optical signal to noise ratio at the receiver side, and then the guideline for counter-act such signal fading is discussed. Finally, we experimentally demonstrate a correlation OTDR with 100km sensing range and 8.2cm spatial resolution (1.2 million resolved points), as a verification of theoretical analysis.

Time complexity and convergence analysis of domain theoretic Picard method

We present an implementation of the domain-theoretic Picard method for solving initial value problems (IVPs) introduced by Edalat and Pattinson [1]. Compared to Edalat and Pattinson's implementation, our algorithm uses a more efficient arithmetic based on an arbitrary precision floating-point library. Despite the additional overestimations due to floating-point rounding, we obtain a similar bound on the convergence rate of the produced approximations. Moreover, our convergence analysis is detailed enough to allow a static optimisation in the growth of the precision used in successive Picard iterations. Such optimisation greatly improves the efficiency of the solving process. Although a similar optimisation could be performed dynamically without our analysis, a static one gives us a significant advantage: we are able to predict the time it will take the solver to obtain an approximation of a certain (arbitrarily high) quality.

Environmental scanning electron microscopy offers real-time morphological analysis of liposomes and niosomes

Liposomes have been imaged using a plethora of techniques. However, few of these methods offer the ability to study these systems in their natural hydrated state without the requirement of drying, staining, and fixation of the vesicles. However, the ability to image a liposome in its hydrated state is the ideal scenario for visualization of these dynamic lipid structures and environmental scanning electron microscopy (ESEM), with its ability to image wet systems without prior sample preparation, offers potential advantages to the above methods. In our studies, we have used ESEM to not only investigate the morphology of liposomes and niosomes but also to dynamically follow the changes in structure of lipid films and liposome suspensions as water condenses on to or evaporates from the sample. In particular, changes in liposome morphology were studied using ESEM in real time to investigate the resistance of liposomes to coalescence during dehydration thereby providing an alternative assay of liposome formulation and stability. Based on this protocol, we have also studied niosome-based systems and cationic liposome/DNA complexes. Copyright © Informa Healthcare.

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.

The design of robust protocols for distributed real-time systems

Modern distributed control systems comprise of a set of processors which are interconnected using a suitable communication network. For use in real-time control environments, such systems must be deterministic and generate specified responses within critical timing constraints. Also, they should be sufficiently robust to survive predictable events such as communication or processor faults. This thesis considers the problem of coordinating and synchronizing a distributed real-time control system under normal and abnormal conditions. Distributed control systems need to periodically coordinate the actions of several autonomous sites. Often the type of coordination required is the all or nothing property of an atomic action. Atomic commit protocols have been used to achieve this atomicity in distributed database systems which are not subject to deadlines. This thesis addresses the problem of applying time constraints to atomic commit protocols so that decisions can be made within a deadline. A modified protocol is proposed which is suitable for real-time applications. The thesis also addresses the problem of ensuring that atomicity is provided even if processor or communication failures occur. Previous work has considered the design of atomic commit protocols for use in non time critical distributed database systems. However, in a distributed real-time control system a fault must not allow stringent timing constraints to be violated. This thesis proposes commit protocols using synchronous communications which can be made resilient to a single processor or communication failure and still satisfy deadlines. Previous formal models used to design commit protocols have had adequate state coverability but have omitted timing properties. They also assumed that sites communicated asynchronously and omitted the communications from the model. Timed Petri nets are used in this thesis to specify and design the proposed protocols which are analysed for consistency and timeliness. Also the communication system is mcxielled within the Petri net specifications so that communication failures can be included in the analysis. Analysis of the Timed Petri net and the associated reachability tree is used to show the proposed protocols always terminate consistently and satisfy timing constraints. Finally the applications of this work are described. Two different types of applications are considered, real-time databases and real-time control systems. It is shown that it may be advantageous to use synchronous communications in distributed database systems, especially if predictable response times are required. Emphasis is given to the application of the developed commit protocols to real-time control systems. Using the same analysis techniques as those used for the design of the protocols it can be shown that the overall system performs as expected both functionally and temporally.

Watermarking biomedical time series data

This thesis addresses the problem of information hiding in low dimensional digital data focussing on issues of privacy and security in Electronic Patient Health Records (EPHRs). The thesis proposes a new security protocol based on data hiding techniques for EPHRs. This thesis contends that embedding of sensitive patient information inside the EPHR is the most appropriate solution currently available to resolve the issues of security in EPHRs. Watermarking techniques are applied to one-dimensional time series data such as the electroencephalogram (EEG) to show that they add a level of confidence (in terms of privacy and security) in an individual’s diverse bio-profile (the digital fingerprint of an individual’s medical history), ensure belief that the data being analysed does indeed belong to the correct person, and also that it is not being accessed by unauthorised personnel. Embedding information inside single channel biomedical time series data is more difficult than the standard application for images due to the reduced redundancy. A data hiding approach which has an in built capability to protect against illegal data snooping is developed. The capability of this secure method is enhanced by embedding not just a single message but multiple messages into an example one-dimensional EEG signal. Embedding multiple messages of similar characteristics, for example identities of clinicians accessing the medical record helps in creating a log of access while embedding multiple messages of dissimilar characteristics into an EPHR enhances confidence in the use of the EPHR. The novel method of embedding multiple messages of both similar and dissimilar characteristics into a single channel EEG demonstrated in this thesis shows how this embedding of data boosts the implementation and use of the EPHR securely.

Steps and bumps:precision extraction of discrete states of molecular machines

We report statistical time-series analysis tools providing improvements in the rapid, precision extraction of discrete state dynamics from time traces of experimental observations of molecular machines. By building physical knowledge and statistical innovations into analysis tools, we provide techniques for estimating discrete state transitions buried in highly correlated molecular noise. We demonstrate the effectiveness of our approach on simulated and real examples of steplike rotation of the bacterial flagellar motor and the F1-ATPase enzyme. We show that our method can clearly identify molecular steps, periodicities and cascaded processes that are too weak for existing algorithms to detect, and can do so much faster than existing algorithms. Our techniques represent a step in the direction toward automated analysis of high-sample-rate, molecular-machine dynamics. Modular, open-source software that implements these techniques is provided.

A new experimental protocol for preferential differentiation of mouse embryonic stem cells into insulin-producing cells

Mouse embiyonic stem (ES) cells have the potential to differentiate into insulin-producing cells, but efficient protocols for in vitro differentiation have not been established. Here we have developed a new optimized four-stage differentiation protocol and compared this with an established reference protocol. The new protocol minimized differentiation towards neuronal progeny, resulting in a population of insulin-producing cells with ß-cell characteristics but lacking neuronal features. The yield of glucagon and somatostatin cells was negligible. Crucial for this improved yield was the removal of a nestin selection step as well as removal of culture supplements that promote differentiation towards the neuronal lineage. Supplementation of the differentiation medium with insulin and fetal calf serum was beneficial for differentiation towards monohor-monal insulin-positive cells. After implantation into diabetic mice these insulin-producing cells produced a time-dependent improvement of the diabetic metabolic state, in contrast to cells differentiated according to the reference protocol. Using a spinner culture instead of an adherent culture of ES cells prevented the differentiation towards insulin-producing cells. Thus, prevention of cell attachment in a spinner culture represents a means to keep ES cells in an undifferentiated state and to inhibit differentiation. In conclusion, this study describes a new optimized four-stage protocol for differentiating ES cells to insulin-producing cells with minimal neuronal cell formation. Copyright © 2008 Cognizant Comm. Corp.

Efficacy and safety of second-generation antipsychotic long-acting injections (SGA LAIs) in maintenance treatment of bipolar disorder:protocol for a systematic review and meta-analysis

INTRODUCTION: Bipolar disorder requires long-term treatment but non-adherence is a common problem. Antipsychotic long-acting injections (LAIs) have been suggested to improve adherence but none are licensed in the UK for bipolar. However, the use of second-generation antipsychotics (SGA) LAIs in bipolar is not uncommon albeit there is a lack of systematic review in this area. This study aims to systematically review safety and efficacy of SGA LAIs in the maintenance treatment of bipolar disorder. METHODS AND ANALYSIS: The protocol is based on Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) and will include only randomised controlled trials comparing SGA LAIs in bipolar. PubMed, EMBASE, CINAHL, Cochrane Library (CENTRAL), PsychINFO, LiLACS, http://www.clinicaltrials.gov will be searched, with no language restriction, from 2000 to January 2016 as first SGA LAIs came to the market after 2000. Manufacturers of SGA LAIs will also be contacted. Primary efficacy outcome is relapse rate or delayed time to relapse or reduction in hospitalisation and primary safety outcomes are drop-out rates, all-cause discontinuation and discontinuation due to adverse events. Qualitative reporting of evidence will be based on 21 items listed on standards for reporting qualitative research (SRQR) focusing on study quality (assessed using the Jadad score, allocation concealment and data analysis), risk of bias and effect size. Publication bias will be assessed using funnel plots. If sufficient data are available meta-analysis will be performed with primary effect size as relative risk presented with 95% CI. Sensitivity analysis, conditional on number of studies and sample size, will be carried out on manic versus depressive symptoms and monotherapy versus adjunctive therapy.

Long-range and high-resolution correlation optical time-domain reflectometry utilizing an all optical chaotic source

A high resolution optical time domain reflectometry (OTDR) based on an all-fiber chaotic source is demonstrated. We analyze the key factors limiting the operational range of such an OTDR, e.g., integral Rayleigh backscattering and the fiber loss, which degrade the optical signal to noise ratio at the receiver side, and then the guideline for counter-act such signal fading is discussed. The experimentally demonstrated correlation OTDR presents ability of 100km sensing range and 8.2cm spatial resolution (1.2 million resolved points), as a verification of the theoretical analysis. To the best of our knowledge, this is the first time that correlation OTDR measurement is performed over such a long distance with such high precision.

Real-time error compensation of a three-axis machine tool using a laser tracker

The concept of measurement-enabled production is based on integrating metrology systems into production processes and generated significant interest in industry, due to its potential to increase process capability and accuracy, which in turn reduces production times and eliminates defective parts. One of the most promising methods of integrating metrology into production is the usage of external metrology systems to compensate machine tool errors in real time. The development and experimental performance evaluation of a low-cost, prototype three-axis machine tool that is laser tracker assisted are described in this paper. Real-time corrections of the machine tool's absolute volumetric error have been achieved. As a result, significant increases in static repeatability and accuracy have been demonstrated, allowing the low-cost three-axis machine tool to reliably reach static positioning accuracies below 35 μm throughout its working volume without any prior calibration or error mapping. This is a significant technical development that demonstrated the feasibility of the proposed methods and can have wide-scale industrial applications by enabling low-cost and structural integrity machine tools that could be deployed flexibly as end-effectors of robotic automation, to achieve positional accuracies that were the preserve of large, high-precision machine tools.

Protocol optimization for the mild detemplation of mesoporous silica nanoparticles resulting in enhanced texture and colloidal stability

Porosity development of mesostructured colloidal silica nanoparticles is related to the removal of the organic templates and co-templates which is often carried out by calcination at high temperatures, 500-600 °C. In this study a mild detemplation method based on the oxidative Fenton chemistry has been investigated. The Fenton reaction involves the generation of OH radicals following a redox Fe3+/Fe2+ cycle that is used as catalyst and H2O2 as oxidant source. Improved material properties are anticipated since the Fenton chemistry comprises milder conditions than calcination. However, the general application of this methodology is not straightforward due to limitations in the hydrothermal stability of the particular system under study. The objective of this work is three-fold: 1) reducing the residual Fe in the resulting solid as this can be detrimental for the application of the material, 2) shortening the reaction time by optimizing the reaction temperature to minimize possible particle agglomeration, and finally 3) investigating the structural and textural properties of the resulting material in comparison to the calcined counterparts. It appears that the Fenton detemplation can be optimized by shortening the reaction time significantly at low Fe concentration. The milder conditions of detemplation give rise to enhanced properties in terms of surface area, pore volume, structural preservation, low Fe residue and high degree of surface hydroxylation; the colloidal particles are stable during storage. A relative particle size increase, expressed as 0.11%·h-1, has been determined.