The Microbial Ecology of Bacterial Vaginosis: A Fine Scale Resolution Metagenomic Analysis

The vaginal microbiota play an important protective role in maintaining the health of women. Disruption of the mutualistic relationship that exists between bacterial communities in the vagina and their hosts can lead to bacterial vaginosis (BV), a condition in which lactic acid producing bacteria are supplanted by a diverse array of strictly anaerobic bacteria. BV has been shown to be an independent risk factor for adverse outcomes including preterm delivery and low infant birth weight, acquisition of sexually transmitted infections and HIV, and development of pelvic inflammatory disease. National surveys indicate the prevalence of BV among U.S. women is 29.2%, and yet, despite considerable effort, the etiology of BV remains unknown. Moreover, there are no broadly effective therapies for the treatment of BV, and reoccurrence is common. In the proposed research we will test the overarching hypothesis that vaginal microbial community dynamics and activities are indicators of risk to BV. To do this, we propose to conduct a high resolution prospective study in which samples collected daily from 200 reproductive-age women over two menstrual cycles are used to capture molecular events that take place before, during, and after the spontaneous remission of BV episodes. We will use modern genomic technologies to obtain the data needed to correlate shifts in vaginal microbial community composition and function, metabolomes, and epidemiological and behavioral metadata with the occurrence of BV to better define the syndrome itself and identify patterns that are predictive of BV. The three specific aims of the research are: (1) Evaluate the association between the dynamics of vaginal microbial communities and risk to BV by characterizing the community composition of vaginal specimens archived from a vaginal douching cessation study in which 33 women self-collected vaginal swabs twice-weekly for 16 weeks; (2) Enroll 135 women in a prospective study in which self-collected vaginal swab samples and secretions are collected daily along with data on the occurrence of BV, vaginal pH, and information on time varying habits and practices; (3) Apply model-based statistical clustering and classification approaches to associate the microbial community composition and function, with metadata and clinical diagnoses of BV. The large body of information generated will facilitate understanding vaginal microbial community dynamics, the etiology of BV, and drive the development of better diagnostic tools for BV. Furthermore, the information will enable a more personalized and effective treatment of BV and ultimately help prevent adverse sequelae associated with this highly prevalent disruption of the vaginal microbiome

Real-time support for high performance aircraft operation

The feasibility of real-time processing schemes using artificial neural networks (ANNs) is investigated. A rationale for digital neural nets is presented and a general processor architecture for control applications is illustrated. Research results on ANN structures for real-time applications are given. Research results on ANN algorithms for real-time control are also shown

Jurisdictional Issues: The EEC Merger Control Regulation, Member State Laws, and Articles 85 and 86

This Article deals with two main issues. One is the division of powers between the European Economic Community and the Member States with regard to merger control after September 21, 1990. The other is the possible application, by the Commission of the European Communities or by national authorities, of Article 85 and 86 of the Treaty Establishing the European Economic Community to mergers covered by Regulation No. 4064/89. The Article casts a brief look at how the dividing line between merges and operations which do not qualify as mergers within the sense of article 3 of the Regulation will be treated in the future

Multiple configuration shell-core structured robotic manipulator with interchangeable mechatronic joints : a thesis presented in partial fulfilment of the requirements for the degree of Masters of Engineering in Mechatronics at Massey University, Turitea Campus, Palmerston North, New Zealand

With the increase of robotic technology utilised throughout industry, the need for skilled labour in this area has increased also. As a result, education dealing with robotics has grown at both the high-school and tertiary educational level. Despite the range of pedagogical robots currently on the market, there seems to be a low variety of these systems specifically related to the types of robotic manipulator arms popular for industrial applications. Furthermore, a fixed-arm system is limited to only serve as an educational supplement for that specific configuration and therefore cannot demonstrate more than one of the numerous industrial-type robotic arms. The Shell-Core structured robotic manipulator concept has been proposed to improve the quality and variety of available pedagogical robotic arm systems on the market. This is achieved by the reconfigurable nature of the concept, which incorporates shell and core structural units to make the construction of at least 5 mainstream industrial arms possible. The platform will be suitable, but not limited to use within the educational robotics industry at high-school and higher educational levels and may appeal to hobbyists. Later dubbed SMILE (Smart Manipulator with Interchangeable Links and Effectors), the system utilises core units to provide either rotational or linear actuation in a single plane. A variety of shell units are then implemented as the body of the robotic arm, serving as appropriate offsets to achieve the required configuration. A prototype consisting of a limited number of ‘building blocks’ was developed for proof-of-concept, found capable of achieving several of the proposed configurations. The outcome of this research is encouraging, with a Massey patent search confirming the unique features of the proposed concept. The prototype system is an economic, easy to implement, plug and play, and multiple-configuration robotic manipulator, suitable for various applications

Modelling the impact of automatic fiscal stabilisers on output stabilisation in South Africa

This paper investigates ways in which an efficiency model like 'DEA Window analysis' can be utilised, under strictly defined conditions, to assess the level of efficiency of automatic fiscal stabilisers (AFS). The size of AFS is obtained through gaps in both revenue and expenditures variables such as tax revenue (current tax on income and wealth), social grants/benefits, and compensation of employees. The results obtained support evidence of AFS action between 1991 and 2005 and explain distinct cointegrating vectors that exist between the obtained efficiency scores and some selected variables, such as a corruption perception index (CPI), a conversion factor (exports), and the level of openness in the economy.South Africa, Automatic Fiscal Stabilisers, Data Envelopment Analysis, Efficiency scores.

Competition through selective inhibitory synchrony

Models of cortical neuronal circuits commonly depend on inhibitory feedback to control gain, provide signal normalization, and to selectively amplify signals using winner-take-all (WTA) dynamics. Such models generally assume that excitatory and inhibitory neurons are able to interact easily, because their axons and dendrites are co-localized in the same small volume. However, quantitative neuroanatomical studies of the dimensions of axonal and dendritic trees of neurons in the neocortex show that this co-localization assumption is not valid. In this paper we describe a simple modification to the WTA circuit design that permits the effects of distributed inhibitory neurons to be coupled through synchronization, and so allows a single WTA to be distributed widely in cortical space, well beyond the arborization of any single inhibitory neuron, and even across different cortical areas. We prove by non-linear contraction analysis, and demonstrate by simulation that distributed WTA sub-systems combined by such inhibitory synchrony are inherently stable. We show analytically that synchronization is substantially faster than winner selection. This circuit mechanism allows networks of independent WTAs to fully or partially compete with each other.Comment: in press at Neural computation; 4 figure

Solving constraint-satisfaction problems with distributed neocortical-like neuronal networks

Finding actions that satisfy the constraints imposed by both external inputs and internal representations is central to decision making. We demonstrate that some important classes of constraint satisfaction problems (CSPs) can be solved by networks composed of homogeneous cooperative-competitive modules that have connectivity similar to motifs observed in the superficial layers of neocortex. The winner-take-all modules are sparsely coupled by programming neurons that embed the constraints onto the otherwise homogeneous modular computational substrate. We show rules that embed any instance of the CSPs planar four-color graph coloring, maximum independent set, and Sudoku on this substrate, and provide mathematical proofs that guarantee these graph coloring problems will convergence to a solution. The network is composed of non-saturating linear threshold neurons. Their lack of right saturation allows the overall network to explore the problem space driven through the unstable dynamics generated by recurrent excitation. The direction of exploration is steered by the constraint neurons. While many problems can be solved using only linear inhibitory constraints, network performance on hard problems benefits significantly when these negative constraints are implemented by non-linear multiplicative inhibition. Overall, our results demonstrate the importance of instability rather than stability in network computation, and also offer insight into the computational role of dual inhibitory mechanisms in neural circuits.Comment: Accepted manuscript, in press, Neural Computation (2018

Collective stability of networks of winner-take-all circuits

The neocortex has a remarkably uniform neuronal organization, suggesting that common principles of processing are employed throughout its extent. In particular, the patterns of connectivity observed in the superficial layers of the visual cortex are consistent with the recurrent excitation and inhibitory feedback required for cooperative-competitive circuits such as the soft winner-take-all (WTA). WTA circuits offer interesting computational properties such as selective amplification, signal restoration, and decision making. But, these properties depend on the signal gain derived from positive feedback, and so there is a critical trade-off between providing feedback strong enough to support the sophisticated computations, while maintaining overall circuit stability. We consider the question of how to reason about stability in very large distributed networks of such circuits. We approach this problem by approximating the regular cortical architecture as many interconnected cooperative-competitive modules. We demonstrate that by properly understanding the behavior of this small computational module, one can reason over the stability and convergence of very large networks composed of these modules. We obtain parameter ranges in which the WTA circuit operates in a high-gain regime, is stable, and can be aggregated arbitrarily to form large stable networks. We use nonlinear Contraction Theory to establish conditions for stability in the fully nonlinear case, and verify these solutions using numerical simulations. The derived bounds allow modes of operation in which the WTA network is multi-stable and exhibits state-dependent persistent activities. Our approach is sufficiently general to reason systematically about the stability of any network, biological or technological, composed of networks of small modules that express competition through shared inhibition.Comment: 7 Figure