Temporal discrimination: Mechanisms and relevance to adult-onset dystonia

Temporal discrimination is the ability to determine that two sequential sensory stimuli are separated in time. For any individual, the temporal discrimination threshold (TDT) is the minimum interval at which paired sequential stimuli are perceived as being asynchronous; this can be assessed, with high test-retest and inter-rater reliability, using a simple psychophysical test. Temporal discrimination is disordered in a number of basal ganglia diseases including adult-onset dystonia, of which the two most common phenotypes are cervical dystonia and blepharospasm. The causes of adult-onset focal dystonia are unknown; genetic, epigenetic, and environmental factors are relevant. Abnormal TDTs in adult-onset dystonia are associated with structural and neurophysiological changes considered to reflect defective inhibitory interneuronal processing within a network which includes the superior colliculus, basal ganglia, and primary somatosensory cortex. It is hypothesized that abnormal temporal discrimination is a mediational endophenotype and, when present in unaffected relatives of patients with adult-onset dystonia, indicates non-manifesting gene carriage. Using the mediational endophenotype concept, etiological factors in adult-onset dystonia may be examined including (i) the role of environmental exposures in disease penetrance and expression; (ii) sexual dimorphism in sex ratios at age of onset; (iii) the pathogenesis of non-motor symptoms of adult-onset dystonia; and (iv) subcortical mechanisms in disease pathogenesis

The Design of a Real-Scale Steel Moment-Resisting Frame for Pseudo-Dynamic Earthquake Testing

Background: Forthe reliable prediction of the non-linear response of structures, severe seismic events have proven to be a challenging task. Although much non-linear analysis software exists, the accuracy of the results depends on the assumptions made in the characterization of the members. Typically, the analytical models are calibrated using experimental observations. With this scope, experimental research remains the most reliable mean for the assessment of the seismic performance of structures, and it is crucial to target the development of new analytical models and design methods. Objective: Quasi-static tests can provide information on the non-linear behaviour of subassemblies, but it is often difficult to relate the imposed force or displacement histories to those that might occur during an earthquake. The pseudo-dynamic method combines an on-line computer simulation with experimental information about the tested structure, providing the application of realistic dynamic response histories. In this paper, the preliminary analysis and the design of a pseudo-dynamic testing facility for the experimental study of a real scale two storeys-two bays steel MRF, with classical and innovative joint details, are shown. Methods: Pushover and Incremental Dynamic Analyses carried out with Seismostruct software estimate the forces and displacements expected at each storey for the selected ground motions. These analyses have been performed by varying the structural detail of the beam-to-column connections. Results / Conclusion: In this paper, the analytical prediction of the performance of two bays-two storeys steel frames equipped with different solutions of beam-to-column joints is focused. Based on the performed analyses, it has been recognized that steel frames with partial strength joints can provide satisfactory performance under severe seismic actions provided that the joints are adequately designed

Search Practices for Discontinuous Innovation: Scale Development and Construct Validation

Managing innovation and particularly searching for new ideas in a steady state environment is really different than in discontinuous conditions where traditional practices and routines may prove ineffective. This paper reviews and empirically explores the field of search strategies and practices for discontinuous innovation and, for the first time, tests the validity of a "Discontinuous Innovation (DI) Search Capacity" construct. Based on a comprehensive literature review on the innovation search stage and on the evidence of more than 80 case studies reported by the Discontinuous Innovation Lab a questionnaire was developed and submitted to a 500 high tech firm sample. Four DI Search dimensions were identified, each consisting of a bundle of interrelated yet distinct practices. We empirically tested the DI Search Capacity and measured it as second-order construct by using the Structural Equation Modelling

F-theory on Quotient Threefolds with (2,0) Discrete Superconformal Matter

We explore 6-dimensional compactifications of F-theory exhibiting (2,0) superconformal theories coupled to gravity that include discretely charged superconformal matter. Beginning with F-theory geometries with Abelian gauge fields and superconformal sectors, we provide examples of Higgsing transitions which break the $U(1)$ gauge symmetry to a discrete remnant in which the matter fields are also non-trivially coupled to a (2,0) SCFT. In the compactification background this corresponds to a geometric transition linking two fibered Calabi-Yau geometries defined over a singular base complex surface. An elliptically fibered Calabi-Yau threefold with non-zero Mordell-Weil rank can be connected to a smooth non-simply connected genus one fibered geometry constructed as a Calabi-Yau quotient. These hyperconifold transitions exhibit multiple fibers in co-dimension 2 over the base.Comment: 60 pages, 11 pages appendices, 18 Figures, 2 Tables, references added, typos corrected, extended introduction, extended discussion of Section 4.3, published versio

Weak-lensing calibration of a stellar mass-based mass proxy for redMaPPer and Voronoi Tessellation clusters in SDSS Stripe 82

We present the first weak lensing calibration of $\mu_{\star}$, a new galaxy cluster mass proxy corresponding to the total stellar mass of red and blue members, in two cluster samples selected from the SDSS Stripe 82 data: 230 redMaPPer clusters at redshift $0.1\leq z<0.33$ and 136 Voronoi Tessellation (VT) clusters at $0.1 \leq z < 0.6$. We use the CS82 shear catalog and stack the clusters in $\mu_{\star}$ bins to measure a mass-observable power law relation. For redMaPPer clusters we obtain $M_0 = (1.77 \pm 0.36) \times 10^{14}h^{-1} M_{\odot}$, $\alpha = 1.74 \pm 0.62$. For VT clusters, we find $M_0 = (4.31 \pm 0.89) \times 10^{14}h^{-1} M_{\odot}$, $\alpha = 0.59 \pm 0.54$ and $M_0 = (3.67 \pm 0.56) \times 10^{14}h^{-1} M_{\odot}$, $\alpha = 0.68 \pm 0.49$ for a low and a high redshift bin, respectively. Our results are consistent, internally and with the literature, indicating that our method can be applied to any cluster finding algorithm. In particular, we recommend that $\mu_{\star}$ be used as the mass proxy for VT clusters. Catalogs including $\mu_{\star}$ measurements will enable its use in studies of galaxy evolution in clusters and cluster cosmology.Comment: Updated to be consistent with the published versio

MicroRNA-155 influences B-cell function through PU.1 in rheumatoid arthritis

MicroRNA-155 (miR-155) is an important regulator of B cells in mice. B cells have a critical role in the pathogenesis of rheumatoid arthritis (RA). Here we show that miR-155 is highly expressed in peripheral blood B cells from RA patients compared with healthy individuals, particularly in the IgD-CD27- memory B-cell population in ACPA+ RA. MiR-155 is highly expressed in RA B cells from patients with synovial tissue containing ectopic germinal centres compared with diffuse synovial tissue. MiR-155 expression is associated reciprocally with lower expression of PU.1 at B-cell level in the synovial compartment. Stimulation of healthy donor B cells with CD40L, anti-IgM, IL-21, CpG, IFN-α, IL-6 or BAFF induces miR-155 and decreases PU.1 expression. Finally, inhibition of endogenous miR-155 in B cells of RA patients restores PU.1 and reduces production of antibodies. Our data suggest that miR-155 is an important regulator of B-cell activation in RA