Identification of a WNT5A-Responsive Degradation Domain in the Kinesin Superfamily Protein KIF26B.

Noncanonical WNT pathways function independently of the β-catenin transcriptional co-activator to regulate diverse morphogenetic and pathogenic processes. Recent studies showed that noncanonical WNTs, such as WNT5A, can signal the degradation of several downstream effectors, thereby modulating these effectors' cellular activities. The protein domain(s) that mediates the WNT5A-dependent degradation response, however, has not been identified. By coupling protein mutagenesis experiments with a flow cytometry-based degradation reporter assay, we have defined a protein domain in the kinesin superfamily protein KIF26B that is essential for WNT5A-dependent degradation. We found that a human disease-causing KIF26B mutation located at a conserved amino acid within this domain compromises the ability of WNT5A to induce KIF26B degradation. Using pharmacological perturbation, we further uncovered a role of glycogen synthase kinase 3 (GSK3) in WNT5A regulation of KIF26B degradation. Lastly, based on the identification of the WNT5A-responsive domain, we developed a new reporter system that allows for efficient profiling of WNT5A-KIF26B signaling activity in both somatic and stem cells. In conclusion, our study identifies a new protein domain that mediates WNT5A-dependent degradation of KIF26B and provides a new tool for functional characterization of noncanonical WNT5A signaling in cells

The Brand Relationship of Cult-Like Following: Developing Scales of Measurement in Apple and Catholic Devotees

The purpose of this research aims to fill in the gap in the religion-brand relationship, and explores what constitutes a cult-like allegiance to a brand, by examining subjects’ relationship to the Apple brand, comparing survey response by subjects who were “devotees” versus “indifferents” to Catholicism and to Apple. This paper uses Ninian Smart’s (1989) “Seven Dimensions of Religion” as a theoretical framework to develop scales of measurement among Apple and Catholic devotees. The contribution of this research is the development of Catholic and Apple scales. The Catholic scale extracted three factors and the Apple scale generated four factors in CFA.

Evaluability assessment: A primer

This paper has two purposes. The first is to increase awareness among policymakers and practitioners for the power and utility of EA, particularly at the state and local level. To this end, the background and rationale for this evaluation strategy is documented. The second is to support and promote its use. The article provides an outline of the procedures for conducting effective EA. While there are detailed resources available (e.g., Nay & Kay, 1982; Smith, 1989; Wholey, 1983), we provide a simplified, accessible presentation of the EA procedure and framework. An example is also provided. Issues and benefits are discussed. Accessed 59,046 times on https://pareonline.net from October 02, 2003 to December 31, 2019. For downloads from January 1, 2020 forward, please click on the PlumX Metrics link to the right

Wafer-Scale Nanopatterning and Translation into High-Performance Piezoelectric Nanowires

The development of a facile method for fabricating one-dimensional, precisely positioned nanostructures over large areas offers exciting opportunities in fundamental research and innovative applications. Large-scale nanofabrication methods have been restricted in accessibility due to their complexity and cost. Likewise, bottom-up synthesis of nanowires has been limited in methods to assemble these structures at precisely defined locations. Nanomaterials such as PbZr_xTi_(1−x)O_3 (PZT) nanowires (NWs)—which may be useful for nonvolatile memory storage (FeRAM), nanoactuation, and nanoscale power generation—are difficult to synthesize without suffering from polycrystallinity or poor stoichiometric control. Here, we report a novel fabrication method which requires only low-resolution photolithography and electrochemical etching to generate ultrasmooth NWs over wafer scales. These nanostructures are subsequently used as patterning templates to generate PZT nanowires with the highest reported piezoelectric performance (d_(eff) ~ 145 pm/V). The combined large-scale nanopatterning with hierarchical assembly of functional nanomaterials could yield breakthroughs in areas ranging from nanodevice arrays to nanodevice powering

Do medical house officers value the health of veterans differently from the health of non-veterans?

BACKGROUND: Little information is available regarding medical residents' perceptions of patients' health-related quality of life. Patients cared for by residents have been shown to receive differing patterns of care at Veterans Affairs facilities than at community or university settings. We therefore examined: 1) how resident physicians value the health of patients; 2) whether values differ if the patient is described as a veteran; and 3) whether residency-associated variables impact values. METHODS: All medicine residents in a teaching hospital were asked to watch a digital video of an actor depicting a 72-year-old patient with mild-moderate congestive heart failure. Residents were randomized to 2 groups: in one group, the patient was described as a veteran of the Korean War, and in the other, he was referred to only as a male. The respondents assessed the patient's health state using 4 measures: rating scale (RS), time tradeoff (TTO), standard gamble (SG), and willingness to pay (WTP). We also ascertained residents' demographics, risk attitudes, residency program type, post-graduate year level, current rotation, experience in a Veterans Affairs hospital, and how many days it had been since they were last on call. We performed univariate and multivariable analyses using the RS, TTO, SG and WTP as dependent variables. RESULTS: Eighty-one residents (89.0% of eligible) participated, with 36 (44.4%) viewing the video of the veteran and 45 (55.6%) viewing the video of the non-veteran. Their mean (SD) age was 28.7 (3.1) years; 51.3% were female; and 67.5% were white. There were no differences in residents' characteristics or in RS, TTO, SG and WTP scores between the veteran and non-veteran groups. The mean RS score was 0.60 (0.14); the mean TTO score was 0.80 (0.20); the mean SG score was 0.91 (0.10); and the median (25th, 75th percentile) WTP was $10,000 ($7600, $20,000) per year. In multivariable analyses, being a resident in the categorical program was associated with assigning higher RS scores, but no residency-associated variables were associated with the TTO, SG or WTP scores. CONCLUSION: Physicians in training appear not to be biased either in favor of or against military veterans when judging the value of a patient's health

An Optical and Infrared Photometric Study of the Young Open Cluster IC 1805 in the Giant H II Region W4

We present deep wide-field optical CCD photometry and mid-infrared Spitzer/IRAC and MIPS 24micron data for about 100,000 stars in the young open cluster IC 1805. The members of IC 1805 were selected from their location in the various color-color and color-magnitude diagrams, and the presence of Halpha emission, mid-infrared excess emission, and X-ray emission. The reddening law toward IC 1805 is nearly normal (R_V = 3.05+/-0.06). However, the distance modulus of the cluster is estimated to be 11.9+/-0.2 mag (d = 2.4+/-0.2 kpc) from the reddening-free color-magnitude diagrams, which is larger than the distance to the nearby massive star-forming region W3(OH) measured from the radio VLBA astrometry. We also determined the age of IC 1805 (tau_MSTO = 3.5 Myr). In addition, we critically compared the age and mass scale from two pre-main-sequence evolution models. The initial mass function with a Salpeter-type slope of Gamma = -1.3+/-0.2 was obtained and the total mass of IC 1805 was estimated to be about 2700+/-200 M_sun. Finally, we found our distance determination to be statistically consistent with the Tycho-Gaia Astrometric Solution Data Release 1, within the errors. The proper motion of the B-type stars shows an elongated distribution along the Galactic plane, which could be explained by some of the B-type stars being formed in small clouds dispersed by previous episodes of star formation or supernova explosions.Comment: 45 pages, 32 figures, 9 tables, accepted for publication in ApJ

The role of snow cover affecting boreal-arctic soil freeze–thaw and carbon dynamics

Northern Hemisphere permafrost affected land areas contain about twice as much carbon as the global atmosphere. This vast carbon pool is vulnerable to accelerated losses through mobilization and decomposition under projected global warming. Satellite data records spanning the past 3 decades indicate widespread reductions (~ 0.8–1.3 days decade−1) in the mean annual snow cover extent and frozen-season duration across the pan-Arctic domain, coincident with regional climate warming trends. How the soil carbon pool responds to these changes will have a large impact on regional and global climate. Here, we developed a coupled terrestrial carbon and hydrology model framework with a detailed 1-D soil heat transfer representation to investigate the sensitivity of soil organic carbon stocks and soil decomposition to climate warming and changes in snow cover conditions in the pan-Arctic region over the past 3 decades (1982–2010). Our results indicate widespread soil active layer deepening across the pan-Arctic, with a mean decadal trend of 6.6 ± 12.0 (SD) cm, corresponding to widespread warming. Warming promotes vegetation growth and soil heterotrophic respiration particularly within surface soil layers (≤ 0.2 m). The model simulations also show that seasonal snow cover has a large impact on soil temperatures, whereby increases in snow cover promote deeper (≥ 0.5 m) soil layer warming and soil respiration, while inhibiting soil decomposition from surface (≤ 0.2 m) soil layers, especially in colder climate zones (mean annual T ≤ −10 °C). Our results demonstrate the important control of snow cover on northern soil freeze–thaw and soil carbon decomposition processes and the necessity of considering both warming and a change in precipitation and snow cover regimes in characterizing permafrost soil carbon dynamics

Attenuation of the association between sugar-sweetened beverages and diabetes risk by adiposity adjustment: a secondary analysis of national health survey data

Purpose: While weight gain and obesity are the dominant factors, dietary sugar and specifically sugar-sweetened beverages (SSB) has been implicated in causing type 2 diabetes (T2DM). We assessed how much of the apparent effect of SSB is explained by adiposity, but not captured by adjustment for BMI, which is a poor index of body fat. Methods: We examined data from 5187 adults (mean age 50.8 years, SD = 16.4, 172 (3.3%) T2DM), from the Scottish Health Survey 2003 and 2008–2010 databases. Logistic regression was used to assess the association between SSB consumption and T2DM (non-insulin treated) and its attenuation (reduction in odds ratios, ORs), after entering published anthropometric indices of adiposity into the regression model, adjusted for age, sex, social class, education, smoking, alcohol consumption and physical activity. Results: Compared with low SSB categories (“less often/never”, once/week or 1–3 times/month), the OR without adiposity adjustment for having T2DM in high SSB consumers (2–3, 4–5, ≥ 6/day) was 2.56 (95% CI 1.12–5.83; p = 0.026). That OR was marginally changed by adjusting for BMI (+ 4.3%), WC (+ 5.5%) or total body fat (− 4.3%), but greatly attenuated by adjusting for estimated %body fat (− 23.4%). These indices had similar influences on the associations between SSB and T2DM combining known T2DM patients with unknown HbA1c > 6.5%, > 48 mmol/mol. Conclusions: Associations between SSB and T2DM are attenuated more markedly by adjustment with estimated %body fat than with BMI, indicating an adiposity effect not captured using BMI. Future research should employ best available estimates of adiposity

Micromachined thick mesh filters for millimeter-wave and terahertz applications

This paper presents several freestanding bandpass mesh filters fabricated using an SU-8-based micromachining technique. The important geometric feature of the filters, which SU8 is able to increase, is the thickness of the cross-shaped micromachined slots. This is five times its width. This thickness offers an extra degree of control over the resonance characteristics. The large thickness not only strengthens the structures, but also enhances the resonance quality factor ( Q-factor). A 0.3-mm-thick, single-layer, mesh filter resonant at 300 GHz has been designed and fabricated and its performance verified. The measured Q-factor is 16.3 and the insertion loss is 0.98 dB. Two multi-layer filter structures have also been demonstrated. The first one is a stacked structure of two single mesh filters producing a double thickness, which achieved a further increased Q-factor of 27. This is over six times higher than a thin mesh filter. The second multilayer filter is an electromagnetically coupled structure forming a two-pole filter. The coupling characteristics are discussed based on experimental and simulation results. These thick mesh filters can potentially be used for sensing and material characterization at millimeter-wave and terahertz frequencies