Collagen Biomarkers for Arthritis Applications

The most common form of chronic arthritis is osteoarthritis (OA) with prevalence as high as 80% after age 75 (Arden and Nevitt, 2006). The incidence of OA is expected to increase as the population ages, increasing the socioeconomic burden of OA. Despite the signifi cant burden of this disease, no drug has been identifi ed that can effectively modify disease progression (Moskowitz and Hooper, 2005; Abadie et al. 2004). However, slowing disease progress and improvement in quality of life may be achieved by behavioral modifi cations, such as weight loss and exercise. Many patients with early OA will progress to disability and joint replacement. Physical examination and radiographic studies are relatively poor means for detecting disease early or predicting progression. Therefore, identifi cation of factors to facilitate early OA diagnosis and prognosis is a major focus of current OA research (Lohmander and Felson, 2004; Lohmander, 2004; Garnero and Delmas, 2003)

A geometric discretisation scheme applied to the Abelian Chern-Simons theory

We give a detailed general description of a recent geometrical discretisation scheme and illustrate, by explicit numerical calculation, the scheme's ability to capture topological features. The scheme is applied to the Abelian Chern-Simons theory and leads, after a necessary field doubling, to an expression for the discrete partition function in terms of untwisted Reidemeister torsion and of various triangulation dependent factors. The discrete partition function is evaluated computationally for various triangulations of $S^3$ and of lens spaces. The results confirm that the discretisation scheme is triangulation independent and coincides with the continuum partition functionComment: 27 pages, 5 figures, 6 tables. in late

The AdS/CFT Correspondence and Logarithmic Corrections to Braneworld Cosmology and the Cardy-Verlinde Formula

The AdS/CFT correspondence is employed to derive logarithmic corrections to the Cardy-Verlinde formula when thermal fluctuations in the Anti-de Sitter black hole are accounted for. The qualitative effect of these corrections on the braneworld cosmology is investigated. The role of such terms in enabling a contracting universe to undergo a bounce is demonstrated. Their influence on the stability of black holes in AdS space and the Hawking-Page-Witten phase transitions is also discussed.Comment: 15 pages, 2 figures. Typographical errors corrected. Conclusions unaltere

Diols and anions can control the formation of an exciplex between a pyridinium boronic acid with an aryl group connected via a propylene linker

The exciplex formation between a pyridinium boronic acid and phenyl group connected via a propylene linker can be monitored using fluorescence. Addition of pinacol affords a cyclic boronate ester with enhanced Lewis acidity that increases the strength of its cation-pi stacking interaction causing a four-fold fluorescence enhancement.Royal Society ; University of Xiamen ; University of Birmingham ; University of Bath ; China Scholarship Council (CSC

Research priorities in the field of posttraumatic pain and disability: Results of a transdisciplinary consensus-generating workshop

© Copyright 2016 David M.Walton et al. Background. Chronic or persistent pain and disability following noncatastrophic \u27musculoskeletal\u27 (MSK) trauma is a pervasive public health problem. Recent intervention trials have provided little evidence of benefit from several specific treatments for preventing chronic problems. Such findings may appear to argue against formal targeted intervention for MSK traumas. However, these negative findings may reflect a lack of understanding of the causal mechanisms underlying the transition from acute to chronic pain, rendering informed and objective treatment decisions difficult. The Canadian Institutes of Health Research (CIHR) Institute ofMusculoskeletalHealth and Arthritis (IMHA) has recently identified better understanding of causalmechanisms as one of three priority foci of their most recent strategic plan. Objectives. A 2-day invitation-only active participation workshop was held inMarch 2015 that included 30 academics, clinicians, and consumers with the purpose of identifying consensus research priorities in the field of trauma-relatedMSK pain and disability, prediction, and prevention. Methods. Conversations were recorded, explored thematically, and member-checked for accuracy. Results. From the discussions, 13 themes were generated that ranged from a focus on identifying causal mechanisms and models to challenges with funding and patient engagement. Discussion. Novel priorities included the inclusion of consumer groups in research from the early conceptualization and design stages and interdisciplinary longitudinal studies that include evaluation of integrated phenotypes and mechanisms

Assembly of N-hexadecyl-pyridinium-4-boronic acid hexafluorophosphate monolayer films with catechol sensing selectivity

The highly water insoluble N-hexadecyl-pyridinium-4-boronic acid hexafluorophosphate is synthesised and investigated for sensor applications. This amphiphilic molecule is immobilised by evaporation of an acetonitrile solution at a basal plane pyrolytic graphite (HOPG) electrode surface and is shown to provide a monolayer film. By varying the amount of deposit partial or full coverage can be achieved. The N-hexadecyl-pyridinium-4-boronic acid hexafluorophosphate monolayer acts as an active receptor for 1,2-dihydroxy-benzene (catechol) derivatives in aqueous media. The ability to bind alizarin red S is investigated and the Langmuirian binding constant determined as a function of pH. It is shown that the immobilised boronic acid monolayer acts as sensor film for a wider range of catechols. A comparison of Langmuirian binding constants for alizarin red S (1.4 x 10(5) mol(-1) dm(3)), catechol (8.4 x 10(4) mol(-1) dm(3)), caffeic acid (7.5 x 10(4) mol(-1) dm(3)), dopamine (1.0 x 10(4) mol(-1) dm(3)), and L-dopa (8 x 10(3) mol(-1) dm(3)) reveals that a combination of hydrophobicity and electrostatic interaction causes considerable selectivity effects.China Scholarship Counci

An Intermittent Live Cell Imaging Screen for siRNA Enhancers and Suppressors of a Kinesin-5 Inhibitor

Kinesin-5 (also known as Eg5, KSP and Kif11) is required for assembly of a bipolar mitotic spindle. Small molecule inhibitors of Kinesin-5, developed as potential anti-cancer drugs, arrest cell in mitosis and promote apoptosis of cancer cells. We performed a genome-wide siRNA screen for enhancers and suppressors of a Kinesin-5 inhibitor in human cells to elucidate cellular responses, and thus identify factors that might predict drug sensitivity in cancers. Because the drug's actions play out over several days, we developed an intermittent imaging screen. Live HeLa cells expressing GFP-tagged histone H2B were imaged at 0, 24 and 48 hours after drug addition, and images were analyzed using open-source software that incorporates machine learning. This screen effectively identified siRNAs that caused increased mitotic arrest at low drug concentrations (enhancers), and vice versa (suppressors), and we report siRNAs that caused both effects. We then classified the effect of siRNAs for 15 genes where 3 or 4 out of 4 siRNA oligos tested were suppressors as assessed by time lapse imaging, and by testing for suppression of mitotic arrest in taxol and nocodazole. This identified 4 phenotypic classes of drug suppressors, which included known and novel genes. Our methodology should be applicable to other screens, and the suppressor and enhancer genes we identified may open new lines of research into mitosis and checkpoint biology