Type Synthesis of 3-DOF Multi-Mode Translational/Spherical Parallel Mechanisms with Lockable Joints

A 3-DOF (degrees-of-freedom) multi-mode translational/spherical PM (parallel mechanism) with lockable joints is a novel reconfigurable PM. It has both 3-DOF spatial translational operation mode and 3-DOF spherical operation mode. This paper presents an approach to the type synthesis of translational/spherical PMs with lockable joints. Using the proposed approach, several 3-DOF translational/spherical PMs are obtained. It is found that these translational/spherical PMs do not encounter constraint singular configurations and self-motion of sub-chain of a leg during reconfiguration. The approach can also be used for synthesizing other classes of multi-mode PMs with lockable joints, multi-mode PMs with variable kinematic joints, partially decoupled PMs, and reconfigurable PMs with a reconfigurable platform.

'Regina v John Terry': The Discursive Construction of an Alleged Racist Event

This article explores the conformation in discourse of a verbal exchange and its subsequent mediatised and legal ramifications. The event concerns an allegedly racist insult directed by high profile English professional footballer John Terry towards another player, Anton Ferdinand, during a televised match in October 2011. The substance of Terry’s utterance, which included the noun phrase ‘fucking black cunt’, was found by a Chief Magistrate not to be a racist insult, although the fact that these actual words were framed within the utterance was not in dispute. The upshot of this ruling was that Terry was acquitted of a racially aggravated public order offence. A subsequent investigation by the regulatory commission of the English Football Association (FA) ruled, almost a year after the event, that Terry was guilty of racially abusing Ferdinand. Terry was banned for four matches and fined £220,000.

It is our contention that this event, played out in legal rulings, social media and print and broadcast media, constitutes a complex web of linguistic structures and strategies in discourse, and as such lends itself well to analysis with a broad range of tools from pragmatics, discourse analysis and cognitive linguistics. Amongst other things, such an analysis can help explain the seemingly anomalous - even contradictory - position adopted in the legal ruling with regard to the speech act status of ‘fucking black cunt’; namely, that the racist content of the utterance was not contested but that the speaker was found not to have issued a racist insult. Over its course, the article addresses this broader issue by making reference to the systemic-functional interpersonal function of language, particularly to the concepts of modality, polarity and modalisation. It also draws on models of verbal irony from linguistic pragmatics, notably from the theory of irony as echoic mention (c.f. Sperber and Wilson, 1981; Wilson and Sperber, 1992). Furthermore, the article makes use of the cognitive-linguistic framework, Text World Theory (c.f. Gavins, 2007; Werth, 1999) to examine the discourse positions occupied by key actors and adapts, from cognitive poetics, the theory of mind-modelling (c.f. Stockwell, 2009) to explore the conceptual means through which these actors discursively negotiate the event.

It is argued that the pragmatic and cognitive strategies that frame the entire incident go a long way towards mitigating the impact of so ostensibly stark an act of racial abuse. Moreover, it is suggested here that the reconciliation of Terry’s action was a result of the confluence of strategies of discourse with relations of power as embodied by the media, the law and perceptions of nationhood embraced by contemporary football culture. It is further proposed that the outcome of this episode, where the FA was put in the spotlight, and where both the conflict and its key antagonists were ‘intranational’, was strongly impelled by the institution of English football and its governing body both to reproduce and maintain social, cultural and ethnic cohesion and to avoid any sense that the event featured a discernable ‘out-group’.

Small animal image-guided radiotherapy: status, considerations and potential for translational impact.

Radiation biology is being transformed by the implementation of small animal image-guided precision radiotherapy into pre-clinical research programmes worldwide. We report on the current status and developments of the small animal radiotherapy field, suggest criteria for the design and execution of effective studies and contend that this powerful emerging technology, used in combination with relevant small animal models, holds much promise for translational impact in radiation oncology.

A new microtubule-targeting compound PBOX-15 inhibits T-cell migration via post-translational modifications of tubulin

The ordered, directional migration of T-lymphocytes is a key process during immune surveillance, immune response, and development. A novel series of pyrrolo-1,5-benzoxazepines have been shown to potently induce apoptosis in variety of human chemotherapy resistant cancer cell lines, indicating their potential in the treatment of both solid tumors and tumors derived from the hemopoietic system. Pyrrolobenzoxazepine 4-acetoxy-5-(1-naphtyl)naphtho[2,3-b]pyrrolo[1,2-d][1,4]-oxazepine (PBOX-15) has been shown to depolymerize tubulin in vitro and in the MCF7 breast cancer cell line. We hypothesized that this may suggest a role for this compound in modulating integrin-induced T-cell migration, which is largely dependent on the microtubule dynamics. Experiments were performed using human T lymphoma cell line Hut78 and peripheral blood T-lymphocytes isolated from healthy donors. We observed that human T-lymphocytes exposed to PBOX-15 have severely impaired ability to polarize and migrate in response to the triggering stimulus generated via cross-linking of integrin lymphocyte function associated antigen-1 receptor. Here, we show that PBOX-15 can dramatically impair microtubule network via destabilization of tubulin resulting in complete loss of the motile phenotype of T-cells. We demonstrate that PBOX-15 inhibitory mechanisms involve decreased tubulin polymerization and its post-translational modifications. Novel microtubule-targeting effects of PBOX-15 can possibly open new horizons in the treatment of overactive inflammatory conditions as well as cancer and cancer metastatic spreading.

Taking risks with translational research

The recent bankruptcy filing by deCODE, a company with an exceptional pedigree in associating genetic variance with disease onset, highlights the commercial risks of translational research. Indeed, deCODE's approach was similar to that adapted by academic researchers who seek to connect genetics and disease. We argue here that neither a purely corporate nor purely academic model is entirely appropriate for such research. Instead, we suggest that the private sector undertake the high-throughput elements of translational research, while the public sector and governments assume the role of providing long-term funding to develop gifted scientists with the confidence to attempt to use genetic data as a stepping stone to a truly mechanistic understanding of complex disease.

Fast Mining of Interesting Phrases from Subsets of Text Corpora

We address the problem of mining interesting phrases from subsets of a text corpus where the subset is specified using a set of features such as keywords that form a query. Previous algorithms for the problem have proposed solutions that involve sifting through a phrase dictionary based index or a document-based index where the solution is linear in either the phrase dictionary size or the size of the document subset. We propose the usage of an independence assumption between query keywords given the top correlated phrases, wherein the pre-processing could be reduced to discovering phrases from among the top phrases per each feature in the query. We then outline an indexing mechanism where per-keyword phrase lists are stored either in disk or memory, so that popular aggregation algorithms such as No Random Access and Sort-merge Join may be adapted to do the scoring at real-time to identify the top interesting phrases. Though such an approach is expected to be approximate, we empirically illustrate that very high accuracies (of over 90%) are achieved against the results of exact algorithms. Due to the simplified list-aggregation, we are also able to provide response times that are orders of magnitude better than state-of-the-art algorithms. Interestingly, our disk-based approach outperforms the in-memory baselines by up to hundred times and sometimes more, confirming the superiority of the proposed method.

Glycosylation of Vitamin D Binding Protein Reduced in Juvenile Idiopathic Arthritis Patients At Risk of Disease Extension.

Background/Purpose:Juvenile idiopathic arthritis (JIA) comprises a poorly understood group of chronic, childhood onset, autoimmune diseases with variable clinical outcomes. We investigated whether profiling of the synovial fluid (SF) proteome by a fluorescent dye based, two-dimensional gel (DIGE) approach could distinguish the subset of patients in whom inflammation extends to affect a large number of joints, early in the disease process. The post-translational modifications to candidate protein markers were verified by a novel deglycosylation strategy.Methods:SF samples from 57 patients were obtained around time of initial diagnosis of JIA. At 1 year from inclusion patients were categorized according to ILAR criteria as oligoarticular arthritis (n=26), extended oligoarticular (n=8) and polyarticular disease (n=18). SF samples were labeled with Cy dyes and separated by two-dimensional electrophoresis. Multivariate analyses were used to isolate a panel of proteins which distinguish patient subgroups. Proteins were identified using MALDI-TOF mass spectrometry with vitamin D binding protein (VDBP) expression and siaylation further verified by immunohistochemistry, ELISA test and immunoprecipitation. Candidate biomarkers were compared to conventional inflammation measure C-reactive protein (CRP). Sialic acid residues were enzymatically cleaved from immunopurified SF VDBP, enriched by hydrophilic interaction liquid chromatography (HILIC) and analysed by mass spectrometry.Results:Hierarchical clustering based on the expression levels of a set of 23 proteins segregated the extended-to-be oligoarticular from the oligoarticular patients. A cleaved isoform of VDBP, spot 873, is present at significantly reduced levels in the SF of oligoarticular patients at risk of disease extension, relative to other subgroups (p<0.05). Conversely total levels of vitamin D binding protein are elevated in plasma and ROC curves indicate an improved diagnostic sensitivity to detect patients at risk of disease extension, over both spot 873 and CRP levels. Sialysed forms of intact immunopurified VDBP were more prevalent in persistent oligoarticular patient synovial fluids.Conclusion:The data indicate that a subset of the synovial fluid proteome may be used to stratify patients to determine risk of disease extension. Reduced conversion of VDBP to a macrophage activation factor may represent a novel pathway contributing to increased risk of disease extension in JIA patients.