Structural insights into the role of the Smoothened cysteine-rich domain in Hedgehog signalling.

Smoothened (Smo) is a member of the Frizzled (FzD) class of G-protein-coupled receptors (GPCRs), and functions as the key transducer in the Hedgehog (Hh) signalling pathway. Smo has an extracellular cysteine-rich domain (CRD), indispensable for its function and downstream Hh signalling. Despite its essential role, the functional contribution of the CRD to Smo signalling has not been clearly elucidated. However, given that the FzD CRD binds to the endogenous Wnt ligand, it has been proposed that the Smo CRD may bind its own endogenous ligand. Here we present the NMR solution structure of the Drosophila Smo CRD, and describe interactions between the glucocorticoid budesonide (Bud) and the Smo CRDs from both Drosophila and human. Our results highlight a function of the Smo CRD, demonstrating its role in binding to small-molecule modulators

Can processes make relationships work? The Triple Helix between structure and action

This contribution seeks to explore how complex adaptive theory can be applied at the conceptual level to unpack Triple Helix models. We use two cases to examine this issue – the Finnish Strategic Centres for Science, Technology & Innovation (SHOKs) and the Canadian Business-led Networks of Centres of Excellence (BL-NCE). Both types of centres are organisational structures that aspire to be business-led, with a considerable portion of their activities driven by (industrial) users’ interests and requirements. Reflecting on the centres’ activities along three dimensions – knowledge generation, consensus building and innovation – we contend that conceptualising the Triple Helix from a process perspective will improve the dialogue between stakeholders and shareholders

LEGUS Discovery of a Light Echo Around Supernova 2012aw

We have discovered a luminous light echo around the normal Type II-Plateau Supernova (SN) 2012aw in Messier 95 (M95; NGC 3351), detected in images obtained approximately two years after explosion with the Wide Field Channel 3 on-board the Hubble Space Telescope (HST) by the Legacy ExtraGalactic Ultraviolet Survey (LEGUS). The multi-band observations span from the near-ultraviolet through the optical (F275W, F336W, F438W, F555W, and F814W). The apparent brightness of the echo at the time was ~21--22 mag in all of these bands. The echo appears circular, although less obviously as a ring, with an inhomogeneous surface brightness, in particular, a prominent enhanced brightness to the southeast. The SN itself was still detectable, particularly in the redder bands. We are able to model the light echo as the time-integrated SN light scattered off of diffuse interstellar dust in the SN environment. We have assumed that this dust is analogous to that in the Milky Way with R_V=3.1. The SN light curves that we consider also include models of the unobserved early burst of light from the SN shock breakout. Our analysis of the echo suggests that the distance from the SN to the scattering dust elements along the echo is ~45 pc. The implied visual extinction for the echo-producing dust is consistent with estimates made previously from the SN itself. Finally, our estimate of the SN brightness in F814W is fainter than that measured for the red supergiant star at the precise SN location in pre-SN images, possibly indicating that the star has vanished and confirming it as the likely SN progenitor.Comment: 10 pages, 9 figures, to appear in the Astrophysical Journa

Hierarchical Star Formation in Nearby LEGUS Galaxies

Hierarchical structure in ultraviolet images of 12 late-type LEGUS galaxies is studied by determining the numbers and fluxes of nested regions as a function of size from ~1 to ~200 pc, and the number as a function of flux. Two starburst dwarfs, NGC 1705 and NGC 5253, have steeper number-size and flux-size distributions than the others, indicating high fractions of the projected areas filled with star formation. Nine subregions in 7 galaxies have similarly steep number-size slopes, even when the whole galaxies have shallower slopes. The results suggest that hierarchically structured star-forming regions several hundred parsecs or larger represent common unit structures. Small galaxies dominated by only a few of these units tend to be starbursts. The self-similarity of young stellar structures down to parsec scales suggests that star clusters form in the densest parts of a turbulent medium that also forms loose stellar groupings on larger scales. The presence of super star clusters in two of our starburst dwarfs would follow from the observed structure if cloud and stellar subregions more readily coalesce when self-gravity in the unit cell contributes more to the total gravitational potential.Comment: 9 pages, 4 figures, accepted for ApJ

Association between Sexual Activity and Human Papillomavirus (HPV) Vaccine Initiation and Completion among College Students

HPV vaccination is most effective if received before initiation of sexual activity. Previous studies suggested that young adult women who were not sexually active were not interested in receiving the vaccine because they did not think it was necessary. Whether this misperception is still prevalent today-and also shared by men-is unknown. This study examined whether sexual activity was associated with HPV vaccine uptake (initiation and completion) among university students. A cross-sectional study was conducted between February and May 2021 among students (n = 951) at a public Midwestern University. Sexual activity was categorized as never or ever had oral and/or vaginal sex. Outcome variables were HPV vaccine initiation, defined as receipt of ≥1 dose, and completion, defined as receipt of ≥3 doses. Multivariable logistic regression models estimated the association between sexual activity and HPV vaccine uptake, adjusting for sociodemographic factors. Approximately 18% of students reported never engaging in sexual activity. Overall, 45.5% initiated the HPV vaccine, and 16.5% completed the vaccine series. After adjusting for covariates, compared to students that reported never engaging in sexual activity, those that had ever engaged in sexual activity were more likely to have initiated the vaccine series (aOR = 2.06, 95% CI: 1.34-3.17); however, no difference was observed for completion. HPV vaccination was low; sexually naïve students were less likely to initiate the HPV vaccine. Since sexually naïve students may benefit from receiving the HPV vaccination, targeted interventions should be implemented towards this population to help increase vaccination rates and prevent HPV-associated diseases

Comparing and contrasting the νμ→ντ\nu_{\mu} \to \nu_{\tau} and νμ→νs\nu_{\mu} \to \nu_s solutions to the atmospheric neutrino problem with SuperKamiokande data

The $\nu_{\mu} \to \nu_{\tau}$ and $\nu_{\mu} \to \nu_s$ solutions to the atmospheric neutrino problem are compared with SuperKamiokande data. The differences between these solutions due to matter effects in the Earth are calculated for the ratio of $\mu$-like to $e$-like events and for up-down flux asymmetries. These quantities are chosen because they are relatively insensitive to theoretical uncertainties in the overall neutrino flux normalisation and detection cross-sections and efficiencies. A $\chi^2$ analysis using these quantities is performed yielding $3\sigma$ ranges which are approximately given by $(0.725 - 1.0, 4 \times 10^{-4} - 2 \times 10^{-2} eV^2)$ and $(0.74 - 1.0, 1 \times 10^{-3} - 2 \times 10^{-2} eV^2)$ for $(\sin^2 2\theta,\Delta m^2)$ for the $\nu_{\mu} \to \nu_{\tau}$ and $\nu_{\mu} \to \nu_s$ solutions, respectively. Values of $\Delta m^2$ smaller than about $2 \times 10^{-3}$ eV$^2$ are disfavoured for the $\nu_{\mu} \to \nu_s$ solution, suggesting that future long baseline experiments should see a positive signal if this scenario is the correct one.Comment: revtex, 22 pages, 12 figure

Geophysical constraints on mirror matter within the Earth

We have performed a detailed investigation of geophysical constraints on the possible admixture of mirror matter inside the Earth. On the basis of the Preliminary Reference Earth Model (PREM) -- the `Standard Model' of the Earth's interior -- we have developed a method which allows one to compute changes in various quantities characterising the Earth (mass, moment of inertia, normal mode frequencies etc.)due to the presence of mirror matter. As a result we have been able to obtain for the first time the direct upper bounds on the possible concentration of the mirror matter in the Earth. In terms of the ratio of the mirror mass to the Earth mass a conservative upper bound is $3.8\times 10^{-3}$. We then analysed possible mechanisms (such as lunar and solar tidal forces, meteorite impacts and earthquakes) of exciting mirror matter oscillations around the Earth centre. Such oscillations could manifest themselves through global variations of the gravitational acceleration at the Earth's surface. We conclude that such variations are too small to be observed. Our results are valid for other types of hypothetical matter coupled to ordinary matter by gravitation only (e.g. the shadow matter of superstring theories).Comment: 25 pages, in RevTeX, to appear in Phys.Rev.