Spatiotemporal and functional characterisation of transient receptor potential vanilloid 4 (TRPV4) in the murine intervertebral disc

The molecular regulators of mechano-transduction in intervertebral disc (IVD) cells are not well understood. The aim of the present study was to characterise the expression and function of the mechano-sensitive ion channel TRPV4 in the IVD. A novel transgenic reporter mouse, in which the endogenous Trpv4 locus drove the expression of LacZ, was used to localise Trpv4 expression at specific stages of spine development [embryonic day (E) 8.5, 12.5, 17.5, postnatal day 1] and time points following skeletal maturity (2.5, 6, 9 and 12 months). The TRPV4-specific agonist GSK1016790A and antagonist GSK2193874 were used to assess the functional response of annulus fibrosus (AF) cells using epifluorescence imaging with Ca2+-sensitive Fura-2 dye and F-actin staining. The effects of TRPV4 agonism and antagonism in mechanically stimulated AF cells were quantified by gene expression analysis. Trpv4 expression was specific to the developing notochord and intervertebral mesenchyme at E12.5. At 2.5, 6 and 9 months, Trpv4 expression was detected in the nucleus pulposus, inner AF, cartilage endplate and vertebral growth plate. AF cells treated with GSK1016790A demonstrated heterogeneity in TRPV4-dependent Ca2+ responses (no response, calcium oscillation or sustained response). TRPV4-induced Ca2+ signalling was associated with Rho/ROCK-dependent actin cytoskeleton remodelling and stress-fibre formation. In AF cells, cyclic-tensile-strain-induced changes in Acan and Prg4 expression were mediated by TRPV4 channel activation. These data establish TRPV4 as an important mechano-sensor regulating IVD mechano-biology

Fermion-scalar interactions with domain wall fermions

Domain wall fermions are defined on a lattice with an extra direction the size of which controls the chiral properties of the theory. When gauge fields are coupled to domain wall fermions the extra direction is treated as an internal flavor space. Here it is found that this is not the case for scalar fields. Instead, the interaction takes place only along the link that connects the boundaries of the extra direction. This reveals a richness in the way different spin particles are coupled to domain wall fermions. As an application, 4-Fermi models are studied using large N techniques and the results are supported by numerical simulations with N=2. It is found that the chiral properties of domain wall fermions in these models are good across a large range of couplings and that a phase with parity-flavor broken symmetry can develop for negative bare masses if the number of sites along the extra direction is finite.Comment: LaTeX, 17 pages, 8 eps figures; comment regarding the width of Aoki phase added in sec. 3; references adde

Deriving social relations among organizational units from process models

For companies to sustain competitive advantages, it is required to redesign and improve business processes continuously by monitoring and analyzing process enactment results. Furthermore, organizational structures must be redesigned according to the changes in business processes. However, there are few scientific approaches to redesigning organizational structures. This paper presents a method for deriving and analyzing organizational relations from process models using social network analysis. Process models contain information on who performs which processes or activities, along with the assignment of organizational units such as departments and roles to related activities. To derive social relations among organizational units from process models, three types of metrics are formally defined: transfer of work metrics, subcontracting metrics, and cooperation metrics. By applying these metrics, various relations among organizational units can be derived and analyzed, which can suggest how organizational structure must be redesigned. To verify the method, the proposed metrics are applied to standard process models of the semiconductor and electronic industry in Korea

Singular measures in circle dynamics

Critical circle homeomorphisms have an invariant measure totally singular with respect to the Lebesgue measure. We prove that singularities of the invariant measure are of Holder type. The Hausdorff dimension of the invariant measure is less than 1 but greater than 0

Health technology assessment of health care innovations in chronic lymphocytic leukaemia and glaucoma care

This doctoral thesis addresses the implications of two health care innovations. One in glaucoma care and one in chronic lymphocytic leukaemia. The implications are expressed in terms of costs and health effects. Furthermore, in the case of one innovation, the implications of relations between professions are also discussed

Cholesterol granuloma in the wall of a mandibular dentigerous cyst: a rare case report

Cholesterol granuloma is an inflammatory reaction to cholesterol crystals deposition. It may develop in a variety of sites including the middle ear, mastoid process or even paranasal sinuses. Very few cases of cholesterol granuloma occurring in the jaws were reported. This report presents a rare case of cholesterol granuloma that developed in the wall of a large mandibular dentigerous cyst. The condition was treated with hemimandibulectomy followed by reconstruction with a free fibular flap

A cost-effectiveness study of ICT training among the visually impaired in the Netherlands

Background: Due to the ageing population, the number of visually impaired people in the Netherlands will increase. To ensure the future availability of services in rehabilitative eye care, we aim to assess the cost-effectiveness of information and communication technology (ICT) training among visually impaired adults from a societal perspective, using primary data from two large rehabilitative eye care providers in the Netherlands. Methods: Participants were asked to fill in a questionnaire, which used six different instruments at three different time points: pre training, post training and three months post training. We investigated whether the participants' quality of life and well-being improved after the training and whether this improvement persisted three months post training. Economic evaluation was conducted by comparing costs and outcomes before and after training. Quality of life and well-being were derived from the EQ-5D and ICECAP-O, respectively. Costs for productivity losses and medical consumption were obtained from the questionnaires. Information regarding the costs of training sessions was provided by the providers. Results: Thirty-eight participants filled in all three questionnaires. The mean age at baseline was 63 years (SD = 16). The effect of ICT training on ICT skills and participants' well-being was positive and persisted three months after the last training session. Assuming these effects remain constant for 10 years, this would result in an incremental cost-effectiveness ratio (ICER) of € 11,000 per quality-adjusted life-year (QALY) and € 8000 per year of well-being gained, when only the costs of ICT training are considered. When the total costs of medical consumption are included, the ICER increases to € 17,000 per QALY gained and € 12,000 per year of well-being gained. Furthermore, when the willingness-to-pay threshold is € 20,000 per year of well-being, the probability that ICT training will be cost-effective is 75% (91% when including only the costs of ICT training). Conclusion: Our study suggests that ICT training among the visually impaired is cost-effective when the effects of ICT training on well-being persist for several years. However, further research involving a larger sample and incorporating long-term effects should be conducted

Channeling in direct dark matter detection I: channeling fraction in NaI (Tl) crystals

The channeling of the ion recoiling after a collision with a WIMP changes the ionization signal in direct detection experiments, producing a larger signal than otherwise expected. We give estimates of the fraction of channeled recoiling ions in NaI (Tl) crystals using analytic models produced since the 1960's and 70's to describe channeling and blocking effects. We find that the channeling fraction of recoiling lattice nuclei is smaller than that of ions that are injected into the crystal and that it is strongly temperature dependent.Comment: 37 pages, 35 figures, Accepted for publication in JCAP on 27 October 2010, Minor revisions: added an appendix, updated references, updated Fig. 9, corrected a few typo

Vortex Plastic Flow, B(x,y,H(t)),M(H(t)),Jc(B(t))B(x,y,H(t)), M(H(t)), J_c(B(t)), Deep in the Bose Glass and Mott-Insulator Regimes

We present simulations of flux-gradient-driven superconducting vortices interacting with strong columnar pinning defects as an external field $H(t)$ is quasi-statically swept from zero through a matching field $B_{\phi}$. We analyze several measurable quantities, including the local flux density $B(x,y,H(t))$, magnetization $M(H(t))$, critical current $J_{c}(B(t))$, and the individual vortex flow paths. We find a significant change in the behavior of these quantities as the local flux density crosses $B_{\phi}$, and quantify it for many microscopic pinning parameters. Further, we find that for a given pin density $J_c(B)$ can be enhanced by maximizing the distance between the pins for $B < B_{\phi}$.Comment: 4 pages, 4 PostScript Figure