The Regulation of Aggrecanase ADAMTS-4 Expression in Human Achilles Tendon and tendon-Derived Cells

Several members of the ADAMTS (A Disintegrin And Metalloproteinase with ThromboSpondin motifs) family have been identified as aggrecanases, whose substrates include versican, the principal large proteoglycan in the tendon extracellular matrix. We have characterized the expression of ADAMTS-4 in human Achilles tendon and tendon-derived cells. ADAMTS-4 mRNA levels were higher in ruptured tendon compared with normal tendon or chronic painful tendinopathy. In tissue extracts probed by Western blotting, mature ADAMTS-4 (68 kDa) was detected only in ruptured tendons, while processed ADAMTS-4 (53 kDa) was detected also in chronic painful tendinopathy and in normal tendon. In cultured Achilles tendon cells, transforming growth factor-ß (TGF-ß) stimulated ADAMTS-4 mRNA expression (typically 20-fold after 24 h), while interleukin-1 induced a smaller, shorter-term stimulation which synergised markedly with that induced by TGF-ß. Increased levels of immunoreactive proteins consistent with mature and processed forms of ADAMTS-4 were detected in TGF-ß-stimulated cells. ADAMTS-4 mRNA was expressed at higher levels by tendon cells in collagen gels than in monolayer cultures. In contrast, the expression of ADAMTS-1 and -5 mRNA was lower in collagen gels compared with monolayers, and these mRNA showed smaller or opposite responses to growth factors and cytokines compared with that of ADAMTS-4 mRNA. We conclude that both ADAMTS-4 mRNA and ADAMTS-4 protein processing may be differentially regulated in normal and damaged tendons and that both the matrix environment and growth factors such as TGF-ß are potentially important factors controlling ADAMTS aggrecanase activities in tendon pathology

Conformal submanifolds, distinguished submanifolds, and integrability

For conformal geometries of Riemannian signature, we provide a comprehensive and explicit treatment of the core local theory for embedded submanifolds of arbitrary dimension. This is based in the conformal tractor calculus and includes a conformally invariant Gauss formula leading to conformal versions of the Gauss, Codazzi, and Ricci equations. It provides the tools for proliferating submanifold conformal invariants, as well for extending to conformally singular Riemannian manifolds the notions of mean curvature and of minimal and CMC submanifolds. A notion of distinguished submanifold is defined by asking the tractor second fundamental form to vanish. We show that for the case of curves this exactly characterises conformal geodesics (a.k.a. conformal circles) while for hypersurfaces it is the totally umbilic condition. So, for other codimensions, this unifying notion interpolates between these extremes, and we prove that in all dimensions this coincides with the submanifold being weakly conformally circular, meaning that ambient conformal circles remain in the submanifold. Stronger notions of conformal circularity are then characterised similarly. Next we provide a very general theory and construction of quantities that are necessarily conserved along distinguished submanifolds. This first integral theory thus vastly generalises the results available for conformal circles in [56]. We prove that any normal solution to an equation from the class of first BGG equations can yield such a conserved quantity, and show that it is easy to provide explicit formulae for these. Finally we prove that the property of being distinguished is also captured by a type of moving incidence relation. This second characterisation is used to show that, for suitable solutions of conformal Killing-Yano equations, a certain zero locus of the solution is necessarily a distinguished submanifold.Comment: 87 page

The room temperature phosphine-free synthesis of near-infrared emitting HgSe quantum dots

Luminescent mercury selenide (HgSe) quantum dots have been synthesised by a phosphine-free method using oleic acid as a capping agent. The modification of experimental conditions such as temperature resulted in particles of various sizes (15–100 nm) and morphologies not previously seen in HgSe, with emission tuneable between 1000 nm and 1350 nm

Optical Studies of Er-doped Yttrium Aluminium Garnet Phosphor Materials

The need for materials application in solid-state lasers, medical devices, and optoelectronic devices has made the investigation of ceramic materials of increasing importance. A detail study of the optical properties of rare earth element typically from luminescent materials when intentionally doped inside the host materials and in particular crystal (such as YAG) is reported for the photoluminescence, power and lifetime measurement. The rare-earth dopants usually form trivalent lanthanide ions and the energy transfer and optical transitions involved originate from 4f-4f transitions of the ions and between these states and the host material. In order to understand the energy transfer processes in more detail we need to better understand the accompanying optical processes that give rise to the emission they display and it is this that forms the focus of the work presented. Following this second (and higher) order processes are considered that lead to upconversion in erbium-doped yttrium aluminum garnet (Er:YAG) materials

Facilitating integrated delivery of services across organisational boundaries: Essential enablers to integration

Introduction: Integrating services is a key tenet to developing services across the United Kingdom. While many aspects ofintegration have been explored, how to facilitate integration of services remains unclear.Method: An exploratory qualitative study was undertaken in 2015 to explore occupational therapists’ perceptions on integratingservice provision across health and social care organisational boundaries. The views of practitioners who had experiencedintegration were sought on a range of aspects of integrating services. This paper focuses on the facilitators for deliveringintegration and the essential enablers are identified.Findings: Numerous factors were noted to facilitate integration and three essential enablers were highlighted. Leadership,communication and joint education were recognised as playing a central role in integrating services across organisationalboundaries; without these three essential enablers, integration is liable to fail.Conclusion: Integration is a process rather than an event; continued emphasis will be required on leadership, communication andjoint education to progress integration achievements made to date

Structural Insights into Differences in Drug-binding Selectivity between Two Forms of Human α1-Acid Glycoprotein Genetic Variants, the A and F1*S Forms

Human α1-acid glycoprotein (hAGP) in serum functions as a carrier of basic drugs. In most individuals, hAGP exists as a mixture of two genetic variants, the F1*S and A variants, which bind drugs with different selectivities. We prepared a mutant of the A variant, C149R, and showed that its drug-binding properties were indistinguishable from those of the wild type. In this study, we determined the crystal structures of this mutant hAGP alone and complexed with disopyramide (DSP), amitriptyline (AMT), and the nonspecific drug chlorpromazine (CPZ). The crystal structures revealed that the drug-binding pocket on the A variant is located within an eight-stranded β-barrel, similar to that found in the F1*S variant and other lipocalin family proteins. However, the binding region of the A variant is narrower than that of the F1*S variant. In the crystal structures of complexes with DSP and AMT, the two aromatic rings of each drug interact with Phe-49 and Phe-112 at the bottom of the binding pocket. Although the structure of CPZ is similar to those of DSP and AMT, its fused aromatic ring system, which is extended in length by the addition of a chlorine atom, appears to dictate an alternative mode of binding, which explains its nonselective binding to the F1*S and A variant hAGPs. Modeling experiments based on the co-crystal structures suggest that, in complexes of DSP, AMT, or CPZ with the F1*S variant, Phe-114 sterically hinders interactions with DSP and AMT, but not CPZ. © 2011 by The American Society for Biochemistry and Molecular Biology, Inc

Virtual Surgical Planning in Subscapular System Free Flap Reconstruction of Midface Defects.

OBJECTIVES: Reconstruction of the midface has many inherent challenges, including orbital support, skull base reconstruction, optimizing midface projection, separation of the nasal cavity and dental rehabilitation. Subscapular system free flaps (SF) have sufficient bone stock to support complex reconstruction and the option of separate soft tissue components. This study analyzes the effect of virtual surgical planning (VSP) in SF for midface on subsite reconstruction, bone segment contact and anatomic position. MATERIALS AND METHODS: Retrospective cohort of patients with midface defects that underwent SF reconstruction at a single tertiary care institution. RESULTS: Nine cases with VSP were compared to fourteen cases without VSP. VSP was associated with a higher number of successfully reconstructed subunits (5.9 vs 4.2, 95% CI of mean difference 0.31-3.04, p = 0.018), a higher number of successful bony contact between segments (2.2 vs 1.4, 95% CI of mean difference 0.0-1.6, p = 0.050), and a higher percent of segments in anatomic position (100% vs 71%, 95% CI of mean difference 2-55%, p = 0.035). When postoperative bone position after VSP reconstruction was compared to preoperative scans, the difference in anteroposterior, vertical and lateral projection compared to the preoperative \u27ideal\u27 bone position was82% of measurements. There were no flap losses. CONCLUSION: VSP may augment SF reconstruction of the midface by allowing for improved subunit reconstruction, bony segment contact and anatomically correct bone segment positioning. VSP can be a useful adjunct for complex midface reconstruction and the benefits should be weighed against cost

Global phylogeography and evolution of chelonid fibropapilloma-associated herpesvirus

A global phylogeny for chelonid fibropapilloma-associated herpesvirus (CFPHV), the most likely aetiological agent of fibropapillomatosis (FP) in sea turtles, was inferred, using dated sequences, through Bayesian Markov chain Monte Carlo analysis and used to estimate the virus evolutionary rate independent of the evolution of the host, and to resolve the phylogenetic positions of new haplotypes from Puerto Rico and the Gulf of Guinea. Four phylogeographical groups were identified: eastern Pacific, western Atlantic/eastern Caribbean, mid-west Pacific and Atlantic. The latter comprises the Gulf of Guinea and Puerto Rico, suggesting recent virus gene flow between these two regions. One virus haplotype from Florida remained elusive, representing either an independent lineage sharing a common ancestor with all other identified virus variants or an Atlantic representative of the lineage giving rise to the eastern Pacific group. The virus evolutionary rate ranged from 1.62x10(-4) to 2.22x10(-4) substitutions per site per year, which is much faster than what is expected for a herpesvirus. The mean time for the most recent common ancestor of the modern virus variants was estimated at 192.90-429.71 years ago, which, although more recent than previous estimates, still supports an interpretation that the global FP pandemic is not the result of a recent acquisition of a virulence mutation(s). The phylogeographical pattern obtained seems partially to reflect sea turtle movements, whereas altered environments appear to be implicated in current FP outbreaks and in the modern evolutionary history of CFPHV.DNER-PR; US NMFS (NMFS-NOAA) [NA08NMF4720436]; US-Fish and Wildlife Service (USFWS); Sociedad Chelonia; WIDECAST; US Environmental Protection Agency (US-EPA); Lisbon Oceanarium, Portugal; Interdisciplinary Research Center for Animal Health of the Faculty of Veterinary Medicine of the Technical University of Lisbon (FMV/TUL)info:eu-repo/semantics/publishedVersio

Geographical information retrieval with ontologies of place

Geographical context is required of many information retrieval tasks in which the target of the search may be documents, images or records which are referenced to geographical space only by means of place names. Often there may be an imprecise match between the query name and the names associated with candidate sources of information. There is a need therefore for geographical information retrieval facilities that can rank the relevance of candidate information with respect to geographical closeness of place as well as semantic closeness with respect to the information of interest. Here we present an ontology of place that combines limited coordinate data with semantic and qualitative spatial relationships between places. This parsimonious model of geographical place supports maintenance of knowledge of place names that relate to extensive regions of the Earth at multiple levels of granularity. The ontology has been implemented with a semantic modelling system linking non-spatial conceptual hierarchies with the place ontology. An hierarchical spatial distance measure is combined with Euclidean distance between place centroids to create a hybrid spatial distance measure. This is integrated with thematic distance, based on classification semantics, to create an integrated semantic closeness measure that can be used for a relevance ranking of retrieved objects