Cellular distribution of the prion protein in palatine tonsils of mule deer (Odocoileus hemionus) and Rocky Mountain elk (Cervus elaphus nelsoni)

Chronic wasting disease (CWD) is a transmissible spongiform encephalopathy (TSE) that affects members of the Cervidae family, including deer (Odocoileus spp.), elk (Cervus Canadensis spp.), and moose (Alces alces spp.). While CWD is a neurodegenerative disease, lymphoid accumulation of the abnormal isoform of the prion protein (PrPSc) is detectable early in the course of infection. It has been shown that a large portion of the PrPSc lymphoid accumulation in infected mule deer takes place on the surface of follicular dendritic cells (FDCs). In mice, FDC expression of PrPC has been shown to be essential for PrPSc accumulation. FDCs have been shown to normally express high levels of PrPC in mice and humans but this has not been examined in natural hosts for CWD. We used double immunofluorescent labeling and confocal microscopy to determine the PrPC expression characteristics of B and T lymphocytes as well as FDCs in palatine tonsils of CWD-negative mule deer and elk. We detected substantial PrPC colocalization with all cellular phenotypic markers used in this study, not just with FDC phenotypic markers

Searching for Dark Photons with Maverick Top Partners

In this paper, we present a model in which an up-type vector-like quark (VLQ) is charged under a new $U(1)_d$ gauge force which kinetically mixes with the SM hypercharge. The gauge boson of the $U(1)_d$ is the dark photon, $\gamma_d$. Traditional searches for VLQs rely on decays into Standard Model electroweak bosons $W,Z$ or Higgs. However, since no evidence for VLQs has been found at the Large Hadron Collider (LHC), it is imperative to search for other novel signatures of VLQs beyond their traditional decays. As we will show, if the dark photon is much less massive than the Standard Model electroweak sector, $M_{\gamma_d}\ll M_Z$, for the large majority of the allowed parameter space the VLQ predominately decays into the dark photon and the dark Higgs that breaks the $U(1)_d$ . That is, this VLQ is a `maverick top partner' with nontraditional decays. One of the appeals of this scenario is that pair production of the VLQ at the LHC occurs through the strong force and the rate is determined by the gauge structure. Hence, the production of the dark photon at the LHC only depends on the strong force and is largely independent of the small kinetic mixing with hypercharge. This scenario provides a robust framework to search for a light dark sector via searches for heavy colored particles at the LHC.Comment: 40 pages and 11 figure

Civic Community Theory and Rates of Violence: A Review of Literature on an Emergent Theoretical Perspective

Civic community theory has emerged in the last 10 years as a middle range theory to explain community variation in rates of crime. It has proven to be particularly powerful for explaining variations in violent crime across rural communities in the U.S. This essay provides a review of the available published literature testing components of the theory. The three main conceptual dimensions of the civic community thesis are outlined, and the nature of the empirical evidence is evaluated. The essay concludes with several suggestions for future research

Role of the unique N-terminal domain of CtBP2 in determining the subcellular localisation of CtBP family proteins

BACKGROUND: CtBP1 and CtBP2 are transcriptional co-repressors that modulate the activity of a large number of transcriptional repressors via the recruitment of chromatin modifiers. Many CtBP-regulated proteins are involved in pathways associated with tumorigenesis, including TGF-beta and Wnt signalling pathways and cell cycle regulators such as RB/p130 and HDM2, as well as adenovirus E1A. CtBP1 and CtBP2 are highly similar proteins, although evidence is emerging that their activity can be differentially regulated, particularly through the control of their subcellular localisation. CtBP2s from diverse species contain a unique N-terminus, absent in CtBP1 that plays a key role in controlling the nuclear-cytoplasmic distribution of the protein.RESULTS: Here we show that amino acids (a.a.) 4-14 of CtBP2 direct CtBP2 into an almost exclusively nuclear distribution in cell lines of diverse origins. Whilst this sequence contains similarity to known nuclear localisation motifs, it cannot drive nuclear localisation of a heterologous protein, but rather has been shown to function as a p300 acetyltransferase-dependent nuclear retention sequence. Here we define the region of CtBP2 required to co-operate with a.a. 4-14 to promote CtBP2 nuclear accumulation as being within a.a. 1-119. In addition, we show that a.a. 120-445 of CtBP2 can also promote CtBP2 nuclear accumulation, independently of a.a. 4-14. Finally, CtBP1 and CtBP2 can form heterodimers, and we show that the interaction with CtBP2 is one mechanism whereby CtBP1 can be recruited to the nucleus.CONCLUSION: Together, these findings represent key distinctions in the regulation of the functions of CtBP family members that may have important implications as to their roles in development, and cell differentiation and survival.<br/

Suppressed dependence of polarization on epitaxial strain in highly polar ferroelectrics

A combined experimental and computational investigation of coupling between polarization and epitaxial strain in highly polar ferroelectric PbZr_0.2Ti_0.8O_3 (PZT) thin films is reported. A comparison of the properties of relaxed (tetragonality c/a = 1.05) and highly-strained (c/a = 1.09) epitaxial films shows that polarization, while being amongst the highest reported for PZT or PbTiO_3 in either film or bulk forms (P_r = 82 microC/cm^2), is almost independent of the epitaxial strain. We attribute this behavior to a suppressed sensitivity of the A-site cations to epitaxial strain in these Pb-based perovskites, where the ferroelectric displacements are already large, contrary to the case of less polar perovskites, such as BaTiO_3. In the latter case, the A-site cation (Ba) and equatorial oxygen displacements can lead to substantial polarization increases.Comment: 4 pages, 3 figure

Atomic-scale compensation phenomena at polar interfaces

The interfacial screening charge that arises to compensate electric fields of dielectric or ferroelectric thin films is now recognized as the most important factor in determining the capacitance or polarization of ultrathin ferroelectrics. Here we investigate using aberration-corrected electron microscopy and density functional theory how interfaces cope with the need to terminate ferroelectric polarization. In one case, we show evidence for ionic screening, which has been predicted by theory but never observed. For a ferroelectric film on an insulating substrate, we found that compensation can be mediated by interfacial charge generated, for example, by oxygen vacancies.Comment: 3 figure

A Time-Motion Study of Emergency and Hospitalist Physicians in a Community Hospital Setting

Introduction: Research has shown that low physician work satisfaction correlates with burnout. Having sufficient time at the patient’s bedside is one element that contributes to work satisfaction. Interruptions, on the other hand, have been implicated as a potential cause of both worker dissatisfaction and clinical error. Better understanding how direct patient care and interruptions affect physician satisfaction may aid in developing future interventions to reduce burnout and improve patient safety. Methods: We conducted an observational, time-motion study to assess how physicians spend their time and correlated these findings to physician satisfaction. This study was conducted in July 2020 (7/1/20 - 7/15/20) at a 591-bed community hospital. A total of 114 emergency medicine (EM) physicians and hospitalists were eligible for participation. Participants were recruited by email. Two trained medical students categorized and recorded the activities of 13 EM and 8 hospitalist physicians and documented the number of interruptions they experienced. An anonymous survey was also employed to investigate participants’ perceptions about interruptions and how they spend their time. We compared the responses from the subjective survey to the objective data to identify activities that may positively or negatively impact participant satisfaction. Results: 18.4% of all eligible physicians participated in the study. In summary, our study showed that EM and hospitalist physicians dedicate roughly double the amount of time to indirect patient care (56.3%) compared to direct patient care (25.8%). EM physicians had more than twice the number of interruptions as hospitalists (every 4.4 minutes vs. every 11.3 minutes). From our survey results, we found no statistically significant difference between the perceived and observed proportion of time spent on direct and indirect patient care for EM physicians (p = 0.62 direct; 0.21 indirect) or hospitalists (p = 0.82 direct; 0.69 indirect). However, there was a statistically significant difference between perceived (overestimated) and observed number of interruptions reported by EM physicians (p = 0.02). Conclusion: The observational data along with the survey results indicate a desire to reduce indirect patient care and increase time at the bedside — suggesting that interventions that target this discrepancy may increase physician work satisfaction and therefore decrease burnout. Additionally, we found that EM physicians far overestimate the actual number of interruptions they experience —however, EM does still engender more than double the interruptions as hospitalists encounter, despite experiencing similar percentages of direct and indirect patient care

Gentrification and Displacement in the San Francisco Bay Area: A Comparison of Measurement Approaches.

Gentrification may play an important role in influencing health outcomes, but few studies have examined these associations. One major barrier to producing empirical evidence to establish this link is that there is little consensus on how to measure gentrification. To address this barrier, we compared three gentrification classification methodologies in relation to their ability to identify neighborhood gentrification in nine San Francisco Bay Area counties: the Freeman method, the Landis method, and the Urban Displacement Project (UDP) Regional Early Warning System. In the 1580 census tracts, 43% of the population had a bachelor's degree or higher. The average median household income was $79,671 in 2013. A comparison of gentrification methodologies revealed that the Landis and Freeman methodologies characterized the vast majority of census tracts as stable, and only 5.2% and 6.1% of tracts as gentrifying. UDP characterized 46.7% of tracts at risk, undergoing, or experiencing advanced stages of gentrification and displacement. There was substantial variation in the geographic location of tracts identified as gentrifying across methods. Given the variation in characterizations of gentrification across measures, studies evaluating associations between gentrification and health should consider using multiple measures of gentrification to examine the robustness of the study findings across measures