Potent inhibition of cartilage biosynthesis by coincubation with joint capsule through an IL-1-independent pathway

The reason for the increased risk for development of osteoarthritis (OA) after acute joint trauma is not well understood, but the mechanically injured cartilage may be more susceptible to degradative mediators secreted by other tissues in the joint. To establish a model for such interactions, we coincubated bovine cartilage tissue explants together with normal joint capsule and found a profound (∼70%) reduction in cartilage proteoglycan biosynthesis. This reduction is due to release by the joint capsule of a heat-labile and non-toxic factor. Surprisingly, while cultured synovium is a canonical source of interleukin-1 (IL-1), blockade either by soluble IL-1 type II receptor (sIL-1r) or IL-1 receptor antagonist (IL-1RA) had no effect. Combined blockade of IL-1 and tumor necrosis factor α (TNF-α) also had no effect. To support the clinical relevance of the findings, we harvested joint capsule from post-mortem human knees. Human joint capsule from a normal adult knee also released a substance that caused an ∼40% decrease in cartilage proteoglycan biosynthesis. Furthermore, this inhibition was not affected by IL-1 blockade with either sIL-1r or IL-1RA. These results suggest that joint capsule tissue from a normal knee joint can release an uncharacterized cytokine that potently inhibits cartilage biosynthetic activity by an IL-1- and TNF-independent pathway.Whitaker FoundationGlaxoSmithKlineNational Institutes of Health (U.S.) (grant AR-45779)National Institutes of Health (U.S.). Specialized Centers Of Interdisciplinary Research (grant ARP50-39239

Comparison of the behaviour of manufactured and other airborne nanoparticles and the consequences for prioritising research and regulation activities

Currently, there are no air quality regulations in force in any part of the world to control number concentrations of airborne atmospheric nanoparticles (ANPs). This is partly due to a lack of reliable information on measurement methods, dispersion characteristics, modelling, health and other environmental impacts. Because of the special characteristics of manufactured (also termed engineered or synthesised) nanomaterials or nanoparticles (MNPs), a substantial increase is forecast for their manufacture and use, despite understanding of safe design and use, and health and environmental implications being in its early stage. This article discusses a number of underlining technical issues by comparing the properties and behaviour of MNPs with anthropogenically produced ANPs. Such a comparison is essential for the judicious treatment of the MNPs in any potential air quality regulatory framework for ANPs

3d/4f Coordination clusters as cooperative catalysts for highly diastereoselective Michael addition reactions

Michael addition (MA) is one of the most well studied chemical transformation in synthetic chemistry. Here, we re-port the synthesis and crystal structures of a library of 3d/4f coordination clusters (CCs) formulated as ZnII2YIII2L4(solv)X(Z)Y and study their catalytic properties towards the MA of nitrostyrenes with barbituric acid deriva-tives. Each CC presents two borderline hard/soft Lewis acidic ZnII centers and two hard Lewis acidic YIII centers in a defect dicubane topology that brings the two different metals into a proximity of {\~{}}3.3 {\AA}. DFT computational studies suggest that these tetrametallic CCs dissociate in solution to give two catalytically active dimers, each containing one 3d and one 4f metal which act cooperatively. The mechanism of catalysis has been corroborated via NMR, EPR and UV-Vis. The present work demonstrates for the first time the successful use of 3d/4f CCs as efficient and high diastereose-lective catalysts in MA reactions

Follistatin-like 3 (FSTL3) mediated silencing of transforming growth factor (TGF ) signaling is essential for testicular aging and regulating testis size

Follistatin-like 3 (FSTL3) is a glycoprotein that binds and inhibits the action of TGFβ ligands such as activin. The roles played by FSTL3 and activin signaling in organ development and homeostasis are not fully understood. The authors show mice deficient in FSTL3 develop markedly enlarged testes that are also delayed in their age-related regression. These FSTL3 knockout mice exhibit increased Sertoli cell numbers, allowing for increased spermatogenesis but otherwise showing normal testicular function. The data show that FSTL3 deletion leads to increased AKT signaling and SIRT1 expression in the testis. This demonstrates a cross-talk between TGFβ ligand and AKT signaling and leads to a potential mechanism for increased cellular survival and antiaging. The findings identify crucial roles for FSTL3 in limiting testis organ size and promoting age-related testicular regression

Observed Reductions in Schistosoma mansoni Transmission from Large-Scale Administration of Praziquantel in Uganda: A Mathematical Modelling Study

To date schistosomiasis control programmes based on chemotherapy have largely aimed at controlling morbidity in treated individuals rather than at suppressing transmission. In this study, a mathematical modelling approach was used to estimate reductions in the rate of Schistosoma mansoni reinfection following annual mass drug administration (MDA) with praziquantel in Uganda over four years (2003-2006). In doing this we aim to elucidate the benefits of MDA in reducing community transmission.Age-structured models were fitted to a longitudinal cohort followed up across successive rounds of annual treatment for four years (Baseline: 2003, TREATMENT: 2004-2006; n = 1,764). Instead of modelling contamination, infection and immunity processes separately, these functions were combined in order to estimate a composite force of infection (FOI), i.e., the rate of parasite acquisition by hosts.MDA achieved substantial and statistically significant reductions in the FOI following one round of treatment in areas of low baseline infection intensity, and following two rounds in areas with high and medium intensities. In all areas, the FOI remained suppressed following a third round of treatment.This study represents one of the first attempts to monitor reductions in the FOI within a large-scale MDA schistosomiasis morbidity control programme in sub-Saharan Africa. The results indicate that the Schistosomiasis Control Initiative, as a model for other MDA programmes, is likely exerting a significant ancillary impact on reducing transmission within the community, and may provide health benefits to those who do not receive treatment. The results obtained will have implications for evaluating the cost-effectiveness of schistosomiasis control programmes and the design of monitoring and evaluation approaches in general

The Murchison Widefield Array: Design Overview

The Murchison Widefield Array (MWA) is a dipole-based aperture array synthesis telescope designed to operate in the 80-300 MHz frequency range. It is capable of a wide range of science investigations, but is initially focused on three key science projects. These are detection and characterization of 3-dimensional brightness temperature fluctuations in the 21cm line of neutral hydrogen during the Epoch of Reionization (EoR) at redshifts from 6 to 10, solar imaging and remote sensing of the inner heliosphere via propagation effects on signals from distant background sources,and high-sensitivity exploration of the variable radio sky. The array design features 8192 dual-polarization broad-band active dipoles, arranged into 512 tiles comprising 16 dipoles each. The tiles are quasi-randomly distributed over an aperture 1.5km in diameter, with a small number of outliers extending to 3km. All tile-tile baselines are correlated in custom FPGA-based hardware, yielding a Nyquist-sampled instantaneous monochromatic uv coverage and unprecedented point spread function (PSF) quality. The correlated data are calibrated in real time using novel position-dependent self-calibration algorithms. The array is located in the Murchison region of outback Western Australia. This region is characterized by extremely low population density and a superbly radio-quiet environment,allowing full exploitation of the instrumental capabilities.Comment: 9 pages, 5 figures, 1 table. Accepted for publication in Proceedings of the IEE

Activation Energy for Grain Growth in Bismuth Coatings

The knowledge of both activation energy and diffusion coefficient is needed for a predictive processing of grain size in coatings. However, for metals as Bismuth there is insufficient information available in the literature for these parameters. To determine these values, a method is adopted wherein an examination of the grain size is conducted for coatings deposited isothermally. The exponent for grain growth with time is determined, thereby enabling quantification of the activation energy and diffusion coefficient. Bismuth coatings that range from 10 {micro}m to 1 mm thick are deposited using electron-beam evaporation onto temperature-controlled substrate surfaces of glass and lithium fluoride. The grain size of each coating is measured upon examination of the microstructure in cross-section using the intercept method. Ideal grain growth is observed over the experimental range of deposition temperatures examined from 317 to 491 K. The activation energy (Q) for grain growth in bismuth is fit as 0.47 eV {center_dot} atom{sup -1} with a diffusion coefficient (D{sub 0}) of 3.3 x 10{sup -4} cm{sup 2} {center_dot} sec{sup -1}

Emergent dynamic chirality in a thermally driven artificial spin ratchet

Modern nanofabrication techniques have opened the possibility to create novel functional materials, whose properties transcend those of their constituent elements. In particular, tuning the magnetostatic interactions in geometrically frustrated arrangements of nanoelements called artificial spin ice1, 2 can lead to specific collective behaviour3, including emergent magnetic monopoles4, 5, charge screening6, 7 and transport8, 9, as well as magnonic response10, 11, 12. Here, we demonstrate a spin-ice-based active material in which energy is converted into unidirectional dynamics. Using X-ray photoemission electron microscopy we show that the collective rotation of the average magnetization proceeds in a unique sense during thermal relaxation. Our simulations demonstrate that this emergent chiral behaviour is driven by the topology of the magnetostatic field at the edges of the nanomagnet array, resulting in an asymmetric energy landscape. In addition, a bias field can be used to modify the sense of rotation of the average magnetization. This opens the possibility of implementing a magnetic Brownian ratchet13, 14, which may find applications in novel nanoscale devices, such as magnetic nanomotors, actuators, sensors or memory cells

The Summary Index of Malaria Surveillance (SIMS): a stable index of malaria within India

<p>Abstract</p> <p>Background</p> <p>Malaria in India has been difficult to measure. Mortality and morbidity are not comprehensively reported, impeding efforts to track changes in disease burden. However, a set of blood measures has been collected regularly by the National Malaria Control Program in most districts since 1958.</p> <p>Methods</p> <p>Here, we use principal components analysis to combine these measures into a single index, the Summary Index of Malaria Surveillance (SIMS), and then test its temporal and geographic stability using subsets of the data.</p> <p>Results</p> <p>The SIMS correlates positively with all its individual components and with external measures of mortality and morbidity. It is highly consistent and stable over time (1995-2005) and regions of India. It includes measures of both <it>vivax </it>and <it>falciparum </it>malaria, with <it>vivax </it>dominant at lower transmission levels and <it>falciparum </it>dominant at higher transmission levels, perhaps due to ecological specialization of the species.</p> <p>Conclusions</p> <p>This measure should provide a useful tool for researchers looking to summarize geographic or temporal trends in malaria in India, and can be readily applied by administrators with no mathematical or scientific background. We include a spreadsheet that allows simple calculation of the index for researchers and local administrators. Similar principles are likely applicable worldwide, though further validation is needed before using the SIMS outside India.</p

Constraints from Solar and Reactor Neutrinos on Unparticle Long-Range Forces

We have investigated the impact of long-range forces induced by unparticle operators of scalar, vector and tensor nature coupled to fermions in the interpretation of solar neutrinos and KamLAND data. If the unparticle couplings to the neutrinos are mildly non-universal, such long-range forces will not factorize out in the neutrino flavour evolution. As a consequence large deviations from the observed standard matter-induced oscillation pattern for solar neutrinos would be generated. In this case, severe limits can be set on the infrared fix point scale, Lambda_u, and the new physics scale, M, as a function of the ultraviolet (d_UV) and anomalous (d) dimension of the unparticle operator. For a scalar unparticle, for instance, assuming the non-universality of the lepton couplings to unparticles to be of the order of a few per mil we find that, for d_UV=3 and d=1.1, M is constrained to be M > O(10^9) TeV (M > O(10^10) TeV) if Lambda_u= 1 TeV (10 TeV). For given values of Lambda_u and d, the corresponding bounds on M for vector [tensor] unparticles are approximately 100 [3/Sqrt(Lambda_u/TeV)] times those for the scalar case. Conversely, these results can be translated into severe constraints on universality violation of the fermion couplings to unparticle operators with scales which can be accessible at future colliders.Comment: 13 pages, 3 figures. Minor changes due to precision in numerical factors and correction in figure labels. References added. Conclusions remain unchange