1,258 research outputs found

    Identification of four residues within the TM4 of the 5-HT2A receptor necessary for 5-HT2A·mGlu2 heteromerization

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    While the etiology is unknown, serotonin and glutamate G protein-coupled receptors (GPCR) neurotransmission dysfunctionality is characteristic of schizophrenia. Previous findings demonstrated that the serotonin 5-hydroxytryptamine 2A (5-HT2A) receptor and the metabotropic glutamate 2 (mGlu2) receptor assemble into a heteromeric complex; however, little is known of the complete structural interface of the heteromer. Through a mutational-based approach, previous research identified Transmembrane domain 4 (TM4) as being responsible for mediating heteromerization in mGlu2 before determining the particular amino acids responsible for the interface. A similar technique was used in this investigation to determine which component of 5-HT2A is responsible for the heterodimeric interface. Here, I identified four residues at the N-terminal of transmembrane domain four essential for the 5-HT2A receptor to form a GPCR heteromer with the mGlu2 receptor in HEK-293 cells. Substitution of these residues (phenylalanine 4.43, leucine 4.44, isoleucine 4.47, and alanine 4.48) leads to a significant reduction of 5-HT2A·mGlu2 receptor complex formation. This finding offers potential targets for future photo-crosslinking investigations to identify the particular residues within the 5-HT2A responsible for mediating the heteromeric interface of the 5-HT2A·mGlu2 complex

    A Characterization of Hedge Fund Exposure to Systematic Risks and Market Correlation

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    Alternative investment vehicles, such as hedge funds, offer potentially high returns for investors willing to stomach the corresponding high-risks and opportunity costs. Additionally, depending on the fund’s methodology, some funds purport to offer limited market exposure in conjunction with their high return potential: they act as true “alternative” investments to the market. The objective of this paper is to analyze hedge funds to determine in what respects they are exposed to the market and systematic risk factors

    Family planning programs in sub-Saharan Africa

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    In the 1980s, signs that sub-Saharan Africans would welcome family planning in numbers sufficient to make a difference in fertility rates were scattered and weak. Pessimists cited formidable cultural and socioeconomic barriers; optimists provided resources for pilot projects, coupled with research to document results and to guide expansion and replication. Among projects with measurable achievements in acceptance of family planning in settings that were less than promising were the Ghana Registered Midwives Project, the Ruhengeri Project in Rwanda, and the Sudan Community-Based Family Health Project. All were associated with the Operations Research Program of Columbia University's Center for Population and Family Health. In Ghana, midwives in private practice were trained and given other support to initiate family planning services. In Rwanda, rural community development volunteers added family planning to their educational activities. In the Sudan, rural catchment areas and work assignments of rural primary health care personnel were changed to introduce family planning and strengthen other child survival services. Positive results were evident from quantitative measures of service delivery and, in Rwanda and the Sudan, from an increase in contraceptive prevalence in the project areas. Other criteria for success included improved management skills, motivation for replicating successful programmatic elements, and potential for continuity. Questions remain as to why attitudes changed, when contraceptive use for family limitation will be practiced widely, and how applicable the experiences reported here are to other locations. These projects do not provide the answers. They do, nonetheless, support an optimistic view for the future offamily planning in sub-Saharan Africa.Health Monitoring&Evaluation,Adolescent Health,ICT Policy and Strategies,Agricultural Knowledge&Information Systems,Early Child and Children's Health

    Real-time optimisation of access control lists for efficient internet packet filtering

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    This paper considers an optimisation problem encountered in the implementation of traffic policies on network routers, namely the ordering of rules in an access control list to minimise or reduce processing time and hence packet latency. The problem is formulated as an objective function with constraints and shown to be NP-complete by translation to a known problem. Exact and heuristic solution methods are introduced, discussed and compared and computational results given. The emphasis throughout is on practical implementation of the optimisation process, that is within the tight constraints of a production network router seeking to reduce latency, on-line, in real-time but without the overhead of significant extra computation

    Traffic Modelling and Simulation Techniques for Evaluating ACL Implementation

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    This paper presents a modelling and simulation framework for analysing Access Control List (ACL) implementation on Internet devices. It uses the established modelling/simulation techniques of abstraction and simplification to isolate the essential components of the system from peripheral issues. As a case study, the viability of a simple real-time optimisation technique is demonstrated

    An argument for simple embedded ACL optimisation

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    The difficulty of efficiently reordering the rules in an Access Control List is considered and the essential optimisation problem formulated. The complexity of exact and sophisticated heuristics is noted along with their unsuitability for real time implementation embedded in the hardware of the network device. A simple alternative is proposed, in which a very limited rule reordering is considered following the processing of each packet. Simulation results are given from a range of traffic types. The method is shown to achieve savings that make its use worthwhile for lists longer than a given number of rules. This number is dependent on traffic characteristics but generally around 25 for typical network conditions

    Extended end-to-end cost metrics for improved dynamic route calculation

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    This paper considers the use of compound cost functions in routing calculations. Using an abstracted version of Cisco’s EIGRP as its basic model, it develops the theoretical principals of optimal end-to-end interior routing then details the limitations of conventional and current implementation. The requirements of an improved system are discussed and proposals for an enhanced Ant Colony Optimisation - DUAL protocol given. A comparative example is used to illustrate the points made and further work needed and other open questions are considered in conclusion. The paper has two purposes. In the main, it provides an analysis of current routing protocols and a model for future ones. In part, however, it is also intended to promote debate into many aspects of Internet routing and its ‘optimality’ in advance of long-term development of the new protocol

    Rule Dependencies in Access Control Lists

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    This paper considers the effects of dependencies between rules in Access Control Lists (ACLs). Dependent rules may not be reordered in an ACL if the policies of the list are to be preserved. This is an obstacle to the optimisation of rule order intended to reduce the time taken matching packets against rules. In this paper, the concept of rule dependency is defined in relation to the problem of minimising processing latency. The concepts of dependence and possible dependence are introduced and the relationship between them considered. Two measures of dependency, the dependency index and the fragmented dependency index are defined and formulated and an upper bound for each is derived. Examples of real-world ACLs are studied and the implications for practical optimisation discussed

    Variable Dielectrics in the Calcium Magnesium Titanate System Characterized with Scanning Microwave Microscopy

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    Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/65839/1/j.1551-2916.2006.00962.x.pd
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