'Leptorapide' - a one-step assay for rapid diagnosis of human leptospirosis

Leptospirosis is a globally important zoonotic infection caused by spirochaetes of the genus Leptospira. It is transmitted to humans by direct contact with infected animals or indirectly via contaminated water. It is mainly a problem of the resource-poor developing countries of the tropical and sub-tropical regions of the world but outbreaks due to an increase in travel and recreational activities have been reported in developed and more industrialized areas of the world. Current methods of diagnosis are costly, time-consuming and require the use of specialized laboratory equipment and personnel. The purpose of this paper is to report the validation of the 'Leptorapide®' test (Linnodee Ltd, Northern Ireland) for the diagnosis of human leptospirosis. It is a simple one-step latex agglutination assay performed using equal volumes of serum sample and antigen-bound latex beads. Evidence of leptospiral antibodies is determined within minutes. Agglutination is scored on a scale of 1-5 and the results interpreted using a score card provided with the kit. Validation has been performed with a large sample size obtained from individuals originating from various parts of the world including Brazil and India. The test has shown sensitivity and specificity values of 97·1% and 94·0%, respectively, relative to the microscopic agglutination test. The results demonstrate that Leptorapide offers a cost-effective and accurate alternative to the more historical methods of antibody detection.

A First Step Towards Cost Functions for Quantum-dot Cellular Automata Designs

Quantum-dot cellular automata (QCA) is potentially a very attractive alternative to CMOS for future digital designs. Circuit designs in QCA have been extensively studied. However, how to properly evaluate the QCA circuits has not been carefully considered. To date, metrics and area-delay cost functions directly mapped from CMOS technology have been used to compare QCA designs, which is inappropriate due to the differences between these two technologies. In this paper, several cost metrics specifically aimed at QCA circuits are studied. It is found that delay, the number of QCA logic gates, and the number and type of crossovers, are important metrics that should be considered when comparing QCA designs. A family of new cost functions for QCA circuits is proposed. As fundamental components in QCA computing arithmetic, QCA adders are reviewed and evaluated with the proposed cost functions. By taking the new cost metrics into account, previous best adders become unattractive and it has been shown that different optimization goals lead to different “best” adders.

The first major step in the peace process’? Exploring the impact of the Anglo-Irish Agreement on Irish Republican thinking

This article supports interpretations of the Anglo-Irish Agreement of 1985 as a significant factor contributing to the development of the Northern Ireland peace process. However, it also emphasises a certain serendipity in the Agreement's effect on northern nationalist, and more specifically republican, politics in the region. In particular, it stresses that a specific interpretation of the Agreement promoted by the Social Democratic and Labour Party inspired a dialogue with republicanism, encouraging an ongoing reappraisal within the latter about the nature of Britain's role in Northern Ireland. This, the article argues, reinforced the movement towards a more political approach that republicans had begun in the 1980s, and encouraged their eventual embrace of a constitutional strategy in the 1990s. However, in advancing this argument, the article notes that such an outcome was far from the minds of the British and Irish officials who negotiated the Anglo-Irish Agreement. The Agreement was intended to marginalise rather than accommodate republicans. Despite this, it provided an inadvertent incentive to draw militant republicanism into the democratic process in Northern Ireland.

The first major step in the peace process’? Exploring the impact of the Anglo-Irish Agreement on Irish republican thinking

This article supports interpretations of the Anglo-Irish Agreement of 1985 as a significant factor contributing towards the development of the Northern Ireland peace process. However, it also emphasises a certain serendipity in the Agreement’s effect on northern nationalist, and more specifically republican, politics in the region. In particular, it stresses that a specific interpretation of the Agreement promoted by the SDLP inspired a dialogue with republicanism, encouraging an ongoing re-appraisal within the latter about the nature of Britain’s role in Northern Ireland. This, the article argues, reinforced the movement towards a more political approach that republicans had begun in the 1980s, and encouraged their eventual embrace of a constitutional strategy in the 1990s. However, in advancing this argument, the article notes that such an outcome was far from the minds of the British and Irish officials who negotiated the Anglo-Irish Agreement. The Agreement was intended to marginalise rather than accommodate republicans. Despite this, it provided an inadvertent incentive to draw militant republicanism into the democratic process in Northern Ireland.

Feature recognition & tool path generation for 5 axis step-nc machining of free form / irregular contoured surfaces

This research paper presents a five step algorithm to generate tool paths for machining Free form / Irregular Contoured Surface(s) (FICS) by adopting STEP-NC (AP-238) format. In the first step, a parametrized CAD model with FICS is created or imported in UG-NX6.0 CAD package. The second step recognizes the features and calculates a Closeness Index (CI) by comparing them with the B-Splines / Bezier surfaces. The third step utilizes the CI and extracts the necessary data to formulate the blending functions for identified features. In the fourth step Z-level 5 axis tool paths are generated by adopting flat and ball end mill cutters. Finally, in the fifth step, tool paths are integrated with STEP-NC format and validated. All these steps are discussed and explained through a validated industrial component.

Integration of cad/ tool path data for 5-axis step-nc machining of free form / irrregular contoured surfaces

This research paper presents the work on feature recognition, tool path data generation and integration with STEP-NC (AP-238 format) for features having Free form / Irregular Contoured Surface(s) (FICS). Initially, the FICS features are modelled / imported in UG CAD package and a closeness index is generated. This is done by comparing the FICS features with basic B-Splines / Bezier curves / surfaces. Then blending functions are caculated by adopting convolution theorem. Based on the blending functions, contour offsett tool paths are generated and simulated for 5 axis milling environment. Finally, the tool path (CL) data is integrated with STEP-NC (AP-238) format. The tool path algorithm and STEP- NC data is tested with various industrial parts through an automated UFUNC plugin.

von Hippel Lindau binding protein 1-mediated degradation of integrase affects HIV-1 gene expression at a postintegration step

HIV-1 integrase, the viral enzyme responsible for provirus integration into the host genome, can be actively degraded by the ubiquitin-proteasome pathway. Here, we identify von Hippel-Lindau binding protein 1(VBP1), a subunit of the prefoldin chaperone, as an integrase cellular binding protein that bridges interaction between integrase and the cullin2 (Cul2)-based von Hippel-Lindau (VHL) ubiquitin ligase. We demonstrate that VBP1 and Cul2/VHL are required for proper HIV-1 expression at a step between integrase-dependent proviral integration into the host genome and transcription of viral genes. Using both an siRNA approach and Cul2/VHL mutant cells, we show that VBP1 and the Cul2/VHL ligase cooperate in the efficient polyubiquitylation of integrase and its subsequent proteasome-mediated degradation. Results presented here support a role for integrase degradation by the prefoldin-VHL-proteasome pathway in the integration-transcription transition of the viral replication cycle.

A two-step approach for the analysis of hybrids in comparative social policy analysis: a nuanced typology of childcare policies

Typologies have represented an important tool for the development of comparative social policy research and continue to be widely used in spite of growing criticism of their ability to capture the complexity of welfare states and their internal heterogeneity. In particular, debates have focused on the presence of hybrid cases and the existence of distinct cross-national pattern of variation across areas of social policy. There is growing awareness around these issues, but empirical research often still relies on methodologies aimed at classifying countries in a limited number of unambiguous types. This article proposes a two-step approach based on fuzzy-set-ideal-type analysis for the systematic analysis of hybrids at the level of both policies (step 1) and policy configurations or combinations of policies (step 2). This approach is demonstrated by using the case of childcare policies in European economies. In the first step, parental leave policies are analysed using three methods – direct, indirect, and combinatory – to identify and describe specific hybrid forms at the level of policy analysis. In the second step, the analysis focus on the relationship between parental leave and childcare services in order to develop an overall typology of childcare policies, which clearly shows that many countries display characteristics normally associated with different types (hybrids and. Therefore, this two-step approach enhances our ability to account and make sense of hybrid welfare forms produced from tensions and contradictions within and between policies.

Optimal 5-step nilpotent quadratic algebras

By the Golod–Shafarevich theorem, an associative algebra $R$ given by $n$ generators and $<n^2/3$ homogeneous quadratic relations is not 5-step nilpotent. We prove that this estimate is optimal. Namely, we show that for every positive integer $n$, there is an algebra $R$ given by $n$ generators and $\lceil n^2/3\rceil$ homogeneous quadratic relations such that $R$ is 5-step nilpotent.

Rational Attenuation of a Morbillivirus by Modulating the Activity of the RNA-Dependent RNA Polymerase

Negative-strand RNA viruses encode a single RNA-dependent RNA polymerase (RdRp) which transcribes and replicates the genome. The open reading frame encoding the RdRp from a virulent wild-type strain of rinderpest virus (RPV) was inserted into an expression plasmid. Sequences encoding enhanced green fluorescent protein (EGFP) were inserted into a variable hinge of the RdRp. The resulting polymerase was autofluorescent, and its activity in the replication/transcription of a synthetic minigenome was reduced. We investigated the potential of using this approach to rationally attenuate a virus by inserting the DNA sequences encoding the modified RdRp into a full-length anti-genome plasmid from which a virulent virus (rRPV(KO)) can be rescued. A recombinant virus, rRPV(KO)L-RRegfpR, which grew at an indistinguishable rate and to an identical titer as rRPV(KO) in vitro, was rescued. Fluorescently tagged polymerase was visible in large cytoplasmic inclusions and beneath the cell membrane. Subcutaneous injection of 10(4) TCID(50) of the rRPV(KO) parental recombinant virus into cattle leads to severe disease symptoms (leukopenia/diarrhea and pyrexia) and death by 9 days postinfection. Animals infected with rRPV(KO)L-RRegfpR exhibited transient leukopenia and mild pyrexia, and the only noticeable clinical signs were moderate reddening of one eye and a slight ocular-nasal discharge. Viruses that expressed the modified polymerase were isolated from peripheral blood lymphocytes and eye swabs. This demonstrates that a virulent morbillivirus can be attenuated in a single step solely by modulating RdRp activity and that there is not necessarily a correlation between virus growth in vitro and in vivo.

Finite-Element Time-Step Coupled Generator, Load, AVR and Brushless Exciter Modelling

This paper presented results from a details and comprehensive simulation using finite element method of the practical operation of an electrical machine. The results it displayed have been used in practice to design more efficient equipment.

2D-drop model applied to the calculation of step formation energies on a (111) substrate

A model is presented for obtaining the step formation energy for metallic islands on (1 1 1) surfaces from Monte Carlo simulations. This model is applied to homo (Cu/Cu(1 1 1), Ag/Ag(1 1 1)) and heteroepitaxy (Ag/Pt(1 1 1)) systems. The embedded atom method is used to represent the interaction between the particles of the system, but any other type of potential could be used as well. The formulation can also be employed to consider the case of other single crystal surfaces, since the higher barriers for atom motion on other surfaces are not a hindrance for the simulation scheme proposed.