Common molecular determinants of local anesthetic, antiarrhythmic, and anticonvulsant block of voltage-gated Na+ channels.

Voltage-gated Na+ channels are the molecular targets of local anesthetics, class I antiarrhythmic drugs, and some anticonvulsants. These chemically diverse drugs inhibit Na+ channels with complex voltage- and frequency-dependent properties that reflect preferential drug binding to open and inactivated channel states. The site-directed mutations F1764A and Y1771A in transmembrane segment IVS6 of type IIA Na+ channel alpha subunits dramatically reduce the affinity of inactivated channels for the local anesthetic etidocaine. In this study, we show that these mutations also greatly reduce the sensitivity of Na+ channels to state-dependent block by the class Ib antiarrhythmic drug lidocaine and the anticonvulsant phenytoin and, to a lesser extent, reduce the sensitivity to block by the class Ia and Ic antiarrhythmic drugs quinidine and flecainide. For lidocaine and phenytoin, which bind preferentially to inactivated Na+ channels, the mutation F1764A reduced the affinity for binding to the inactivated state 24.5-fold and 8.3-fold, respectively, while Y1771A had smaller effects. For quinidine and flecainide, which bind preferentially to the open Na+ channels, the mutations F1764A and Y1771A reduced the affinity for binding to the open state 2- to 3-fold. Thus, F1764 and Y1771 are common molecular determinants of state-dependent binding of diverse drugs including lidocaine, phenytoin, flecainide, and quinidine, suggesting that these drugs interact with a common receptor site. However, the different magnitude of the effects of these mutations on binding of the individual drugs indicates that they interact in an overlapping, but nonidentical, manner with a common receptor site. These results further define the contributions of F1764 and Y1771 to a complex drug receptor site in the pore of Na+ channels.

Existence of complementary pairs of proportionally balanced designs

Proportionally balanced designs (pi BDs) were introduced by Gray and Matters in response to a need for the allocation of markers of the Queensland Core Skills Test to have a certain property. Subsequent papers extended the theoretical results relating to such designs and provided further instances and general constructions. This work focused on designs comprising blocks of precisely two sizes, and when each variety occurs with one of precisely two possible frequencies. Two designs based on the set V of varieties are complementary if, whenever B is a block of one, then its complement with regard to the set V is a block of the other. Here we present necessary conditions for the existence of complementary pairs of such pi BDs and provide lists of some restricted parameter sets satisfying these necessary conditions. The lists are arranged according to the number of blocks. We demonstrate that not all of these parameter sets give rise to designs. However we establish by construction of the sets of blocks that, for every feasible number of blocks less than or equal to 100, with the possible exception of 63, there exists at least one pair of complementary pi BDs. We also investigate the conditions under which the complementary design can be isomorphic to the original design, and again provide a list of feasible parameters for pairs of such designs with at most 400 blocks.

Embedding a restricted class of partial K-4-designs

Given a partial K-4-design (X, P), if x is an element of X is a vertex which occurs in exactly one block of P, then call x a free vertex. In this paper, a technique is described for obtaining a cubic embedding of any partial K-4-design with the property that every block in the partial design contains at least two free vertices.

Interface adaptor logic: A new model for interfacing peripherals in IP based designs

The introduction of standard on-chip buses has eased integration and boosted the production of IP functional cores. However, once an IP is bus specific retargeting to a different bus is time-consuming and tedious, and this reduces the reusability of the bus-specific IP. As new bus standards are introduced and different interconnection methods are proposed, this problem increases. Many solutions have been proposed, however these solutions either limit the IP block performance or are restricted to a particular platform. A new concept is presented that can connect IP blocks to a wide variety of interface architectures with low overhead. This is achieved through the use a special interface adaptor logic layer.

A comparative study of block scheduling and traditional scheduling on academic achievement

The purpose of this study was to evaluate the effectiveness of an alternate day block schedule design (n = 419) versus a traditional six-period schedule design (n = 623) on the academic achievement of the graduating classes in two schools in which the design was used respectively. Academic achievement was measured by (a) two standardized tests: the Florida Comprehensive Assessment Test Sunshine State Standards (FCAT-SSS) in mathematics and reading for 9th and 10th grade and the Scholastic Reading Inventory Test (SRI) for 9 th, 10th, and 11th grade; (b) three school grades: the mathematics final course grades for 9th, 10th, and 11th grade, the English final course grades for 9th, 10th, 11th, and 12th grade and the graduating GPA. A total of five repeated measure analyses of variance (ANOVAs) were conducted to analyze the difference between the two schools (representing the two designs) with respect to five achievement indicators (FCAT-SSS mathematics scores, FCAT-SSS reading scores, SRI scores, mathematics final course grades, and English final course grades). The between-subject factor for the five ANOVAs was the schedule design and the within-subject factor was the time the tests were taken or the time the course grades were issued. T-tests were performed on all eighth grade achievement indicators to ensure there were no significant differences in achievement between the two cohorts prior to entering high school. An independent samples t-test was conducted to analyze the difference between the two schedule designs with respect to graduating GPA. Achievement in the alternate day block schedule design was significantly higher than in the traditional six-period schedule design for some of the locally assigned school grades. The difference between the two types of schedule designs was not significant for the standardized measures (the FCAT-SSS in reading and mathematics and the SRI). This study concludes that the use of an alternate day block schedule design can be considered an educational tool that can help improve the academic achievement of students as measured by local indicators of achievement; but, apparently the design is not an important factor in achievement as measured by state examinations such as the FCAT-SSS or the SRI.

Conceptual designs of multi-degree of freedom compliant parallel manipulators composed of wire-beam based compliant mechanisms

This paper proposes conceptual designs of multi-degree(s) of freedom (DOF) compliant parallel manipulators (CPMs) including 3-DOF translational CPMs and 6-DOF CPMs using a building block based pseudo-rigid-body-model (PRBM) approach. The proposed multi-DOF CPMs are composed of wire-beam based compliant mechanisms (WBBCMs) as distributed-compliance compliant building blocks (CBBs). Firstly, a comprehensive literature review for the design approaches of compliant mechanisms is conducted, and a building block based PRBM is then presented, which replaces the traditional kinematic sub-chain with an appropriate multi-DOF CBB. In order to obtain the decoupled 3-DOF translational CPMs (XYZ CPMs), two classes of kinematically decoupled 3-PPPR (P: prismatic joint, R: revolute joint) translational parallel mechanisms (TPMs) and 3-PPPRR TPMs are identified based on the type synthesis of rigid-body parallel mechanisms, and WBBCMs as the associated CBBs are further designed. Via replacing the traditional actuated P joint and the traditional passive PPR/PPRR sub-chain in each leg of the 3-DOF TPM with the counterpart CBBs (i.e. WBBCMs), a number of decoupled XYZ CPMs are obtained by appropriate arrangements. In order to obtain the decoupled 6-DOF CPMs, an orthogonally-arranged decoupled 6-PSS (S: spherical joint) parallel mechanism is first identified, and then two example 6-DOF CPMs are proposed by the building block based PRBM method. It is shown that, among these designs, two types of monolithic XYZ CPM designs with extended life have been presented.

Tailoring of interface of polypropylene/polystyrene/carbon nanofibre composites by polystyrene-block-poly(ethylene-ran-butylene)-block-polystyrene

Mechanical and physical properties of polypropylene (PP)/polystyrene (PS) blend, PP/PS/polystyrene-block-poly(ethylene-ran-butylene)-block-polystyrene (SEBS) ternary blend and their composites with carbon nanofibers (CNF) were investigated. Composites of ternary blend exhibited superior properties compared to those of binary blends. Mechanical performance of nanocomposites was intimately related to their phase morphology. PP/PS/SEBS/0.1 wt% CNF hybrid composites exhibited excellent impact strength (Four-fold increase compared to PP/PS blend) and ductility (12-fold increase in elongation at break, with respect to PP/PS blend). Moreover, these composites displayed good tensile strength and modulus (15% increase in Young's modulus, compared to PP/PS/SEBS blend) and are suitable for various end-use applications including automobile applications. Although crystallinity of PP phase is decreased by the incorporation of CNF, thermal stability of the composites remained almost unaffected. Contact angle measurements revealed that ternary composites exhibited maximum hydrophobicity.

Security metrics for object-oriented class designs

Measuring quality attributes of object-oriented designs (e.g. maintainability and performance) has been covered by a number of studies. However, these studies have not considered security as much as other quality attributes. Also, most security studies focus at the level of individual program statements. This approach makes it hard and expensive to discover and fix vulnerabilities caused by design errors. In this work, we focus on the security design of an object oriented application and define a number of security metrics. These metrics allow designers to discover and fix security vulnerabilities at an early stage, and help compare the security of various alternative designs. In particular, we propose seven security metrics to measure Data Encapsulation (accessibility) and Cohesion (interactions) of a given object-oriented class from the point of view of potential information flow.

Difference-based meta-analytic procedures for between-participant and/or within-participant designs : a tutorial review for sports and exercise scientists

The aim of this paper is to provide a contemporary summary of statistical and non-statistical meta-analytic procedures that have relevance to the type of experimental designs often used by sport scientists when examining differences/change in dependent measure(s) as a result of one or more independent manipulation(s). Using worked examples from studies on observational learning in the motor behaviour literature, we adopt a random effects model and give a detailed explanation of the statistical procedures for the three types of raw score difference-based analyses applicable to between-participant, within-participant, and mixed-participant designs. Major merits and concerns associated with these quantitative procedures are identified and agreed methods are reported for minimizing biased outcomes, such as those for dealing with multiple dependent measures from single studies, design variation across studies, different metrics (i.e. raw scores and difference scores), and variations in sample size. To complement the worked examples, we summarize the general considerations required when conducting and reporting a meta-analysis, including how to deal with publication bias, what information to present regarding the primary studies, and approaches for dealing with outliers. By bringing together these statistical and non-statistical meta-analytic procedures, we provide the tools required to clarify understanding of key concepts and principles.

Space-frequency block code with matched rotation for MIMO-OFDM system with limited feedback

This paper presents a novel matched rotation precoding (MRP) scheme to design a rate one space-frequency block code (SFBC) and a multirate SFBC for MIMO-OFDM systems with limited feedback. The proposed rate one MRP and multirate MRP can always achieve full transmit diversity and optimal system performance for arbitrary number of antennas, subcarrier intervals, and subcarrier groupings, with limited channel knowledge required by the transmit antennas. The optimization process of the rate one MRP is simple and easily visualized so that the optimal rotation angle can be derived explicitly, or even intuitively for some cases. The multirate MRP has a complex optimization process, but it has a better spectral efficiency and provides a relatively smooth balance between system performance and transmission rate. Simulations show that the proposed SFBC with MRP can overcome the diversity loss for specific propagation scenarios, always improve the system performance, and demonstrate flexible performance with large performance gain. Therefore the proposed SFBCs with MRP demonstrate flexibility and feasibility so that it is more suitable for a practical MIMO-OFDM system with dynamic parameters.

Schematic Representation of Case Study Research Designs

Aim. The paper is a report of a study to demonstrate how the use of schematics can provide procedural clarity and promote rigour in the conduct of case study research. Background. Case study research is a methodologically flexible approach to research design that focuses on a particular case – whether an individual, a collective or a phenomenon of interest. It is known as the 'study of the particular' for its thorough investigation of particular, real-life situations and is gaining increased attention in nursing and social research. However, the methodological flexibility it offers can leave the novice researcher uncertain of suitable procedural steps required to ensure methodological rigour. Method. This article provides a real example of a case study research design that utilizes schematic representation drawn from a doctoral study of the integration of health promotion principles and practices into a palliative care organization. Discussion. The issues discussed are: (1) the definition and application of case study research design; (2) the application of schematics in research; (3) the procedural steps and their contribution to the maintenance of rigour; and (4) the benefits and risks of schematics in case study research. Conclusion. The inclusion of visual representations of design with accompanying explanatory text is recommended in reporting case study research methods.