Test method for telescopes using a point source at a finite distance

A test method for telescopes that makes use of a focused ring formed by an annular aperture when using a point source at a finite distance is evaluated theoretically and experimentally. The results show that the concept can be applied to near-normal, as well as grazing incidence. It is particularly suited for X-ray telescopes because of their intrinsically narrow annular apertures, and because of the largely reduced diffraction effects

Atomic structures of fibrillar segments of hIAPP suggest tightly mated β-sheets are important for cytotoxicity.

hIAPP fibrils are associated with Type-II Diabetes, but the link of hIAPP structure to islet cell death remains elusive. Here we observe that hIAPP fibrils are cytotoxic to cultured pancreatic β-cells, leading us to determine the structure and cytotoxicity of protein segments composing the amyloid spine of hIAPP. Using the cryoEM method MicroED, we discover that one segment, 19-29 S20G, forms pairs of β-sheets mated by a dry interface that share structural features with and are similarly cytotoxic to full-length hIAPP fibrils. In contrast, a second segment, 15-25 WT, forms non-toxic labile β-sheets. These segments possess different structures and cytotoxic effects, however, both can seed full-length hIAPP, and cause hIAPP to take on the cytotoxic and structural features of that segment. These results suggest that protein segment structures represent polymorphs of their parent protein and that segment 19-29 S20G may serve as a model for the toxic spine of hIAPP

Who Should Decide? Decision-Making Preferences for Primary HPV Testing for Cervical Cancer Screening Among U.S. Women

Revised U.S. guidelines for cervical cancer screening provide the option of primary human papillomavirus (HPV) testing, Pap testing, or co-testing. Primary HPV testing has not yet been an option for American women, and women may be reluctant to change screening methods. The purpose of this study was to assess correlates of women’s preferences for primary HPV testing decision-making (self, provider, or shared) for cervical cancer screening. Women, aged 30-65, completed an online survey in June of 2018 (n = 812). The outcome variable was preference for decision-making for an HPV test instead of a Pap test on a scale of, healthcare provider, me, or shared. Predictor variables included testing attitudes, social norms, information seeking, previous screening, and socio-demographics. Women who disagreed that people important to them think that they should get the HPV test instead of a Pap test, who were not willing to receive an HPV test instead of a Pap test, and who did not receive HPV vaccinations were less likely to include a provider in their decision-making. In contrast, women who were not up-to-date with their cervical cancer screenings, who had some college or technical level education, or who were over 50 years of age were more likely to prefer to have a healthcare provider included in their decision-making process. While some variation was discovered, women mostly preferred a shared decision or personal decision for HPV testing. Resources to facilitate the decision-making process about this new option for cervical cancer screening are needed

An innovative quality improvement curriculum for third-year medical students

Background: Competence in quality improvement (QI) is a priority for medical students. We describe a self-directed QI skills curriculum for medical students in a 1-year longitudinal integrated third-year clerkship: an ideal context to learn and practice QI. Methods: Two groups of four students identified a quality gap, described existing efforts to address the gap, made quantifying measures, and proposed a QI intervention. The program was assessed with knowledge and attitude surveys and a validated tool for rating trainee QI proposals. Reaction to the curriculum was assessed by survey and focus group. Results: Knowledge of QI concepts did not improve (mean knowledge score±SD): pre: 5.9±1.5 vs. post: 6.6±1.3, p=0.20. There were significant improvements in attitudes (mean topic attitude score±SD) toward the value of QI (pre: 9.9±1.8 vs. post: 12.6±1.9, p=0.03) and confidence in QI skills (pre: 13.4±2.8 vs. post: 16.1±3.0, p=0.05). Proposals lacked sufficient analysis of interventions and evaluation plans. Reaction was mixed, including appreciation for the experience and frustration with finding appropriate mentorship. Conclusion: Clinical-year students were able to conduct a self-directed QI project. Lack of improvement in QI knowledge suggests that self-directed learning in this domain may be insufficient without targeted didactics. Higher order skills such as developing measurement plans would benefit from explicit instruction and mentorship. Lessons from this experience will allow educators to better target QI curricula to medical students in the clinical years

Exact Thermodynamics of the Double sinh-Gordon Theory in 1+1-Dimensions

We study the classical thermodynamics of a 1+1-dimensional double-well sinh-Gordon theory. Remarkably, the Schrodinger-like equation resulting from the transfer integral method is quasi-exactly solvable at several temperatures. This allows exact calculation of the partition function and some correlation functions above and below the short-range order (``kink'') transition, in striking agreement with high resolution Langevin simulations. Interesting connections with the Landau-Ginzburg and double sine-Gordon models are also established.Comment: 4 pages, 3 figures (embedded using epsf), uses RevTeX plus macro (included). Minor revision to match journal version, Phys. Rev. Lett. (in press

Noise-Induced Phase Space Transport in Two-Dimensional Hamiltonian Systems

First passage time experiments were used to explore the effects of low amplitude noise as a source of accelerated phase space diffusion in two-dimensional Hamiltonian systems, and these effects were then compared with the effects of periodic driving. The objective was to quantify and understand the manner in which ``sticky'' chaotic orbits that, in the absence of perturbations, are confined near regular islands for very long times, can become ``unstuck'' much more quickly when subjected to even very weak perturbations. For both noise and periodic driving, the typical escape time scales logarithmically with the amplitude of the perturbation. For white noise, the details seem unimportant: Additive and multiplicative noise typically have very similar effects, and the presence or absence of a friction related to the noise by a Fluctuation-Dissipation Theorem is also largely irrelevant. Allowing for colored noise can significantly decrease the efficacy of the perturbation, but only when the autocorrelation time becomes so large that there is little power at frequencies comparable to the natural frequencies of the unperturbed orbit. Similarly, periodic driving is relatively inefficient when the driving frequency is not comparable to these natural frequencies. This suggests strongly that noise-induced extrinsic diffusion, like modulational diffusion associated with periodic driving, is a resonance phenomenon. The logarithmic dependence of the escape time on amplitude reflects the fact that the time required for perturbed and unperturbed orbits to diverge a given distance scales logarithmically in the amplitude of the perturbation.Comment: 15 pages, including 13 Figures and 1 Table, uses Phys. Rev. macro

Chaos and chaotic phase mixing in cuspy triaxial potentials

This paper investigates chaos and chaotic phase mixing in triaxial Dehnen potentials which have been proposed to describe realistic ellipticals. Earlier work is extended by exploring the effects of (1) variable axis ratios, (2) `graininess' associated with stars and bound substructures, idealised as friction and white noise, and (3) large-scale organised motions presumed to induce near-random forces idealised as coloured noise with finite autocorrelation time. Three important conclusions are: (1) not all the chaos can be attributed to the cusp; (2) significant chaos can persist even for axisymmetric systems; and (3) introducing a supermassive black hole can increase both the relative number of chaotic orbits and the size of the largest Lyapunov exponent. Sans perturbations, distribution functions associated with initially localised chaotic ensembles evolve exponentially towards a nearly time-independent form at a rate L that correlates with the finite time Lyapunov exponents associated with the evolving orbits. Perturbations accelerate phase space transport by increasing the rate of phase mixing in a given phase space region and by facilitating diffusion along the Arnold web that connects different phase space regions, thus facilitating an approach towards a true equilibrium. The details of the perturbation appear unimportant. All that matters are the amplitude and the autocorrelation time, upon which there is a weak logarithmic dependence. Even comparatively weak perturbations can increase L by a factor of three or more, a fact that has potentially significant implications for violent relaxation.Comment: 17 pages, 17 figures -- revised and extended manuscript to appear in Monthly Notices of the Royal Astronomical Societ

Phase space transport in cuspy triaxial potentials: Can they be used to construct self-consistent equilibria?

(Abridged) This paper studies chaotic orbit ensembles evolved in triaxial generalisations of the Dehnen potential which have been proposed to model ellipticals with a strong density cusp that manifest significant deviations from axisymmetry. Allowance is made for a possible supermassive black hole, as well as low amplitude friction, noise, and periodic driving which can mimic irregularities associated with discreteness effects and/or an external environment. The degree of chaos is quantified by determining how (1) the relative number of chaotic orbits and (2) the size of the largest Lyapunov exponent depend on the steepness of the cusp and the black hole mass, and (3) the extent to which Arnold webs significantly impede phase space transport, both with and without perturbations. In the absence of irregularities, chaotic orbits tend to be extremely `sticky,' so that different pieces of the same chaotic orbit can behave very differently for 10000 dynamical times or longer, but even very low amplitude perturbations can prove efficient in erasing many -- albeit not all -- these differences. The implications thereof are discussed both for the structure and evolution of real galaxies and for the possibility of constructing approximate near-equilibrium models using Schwarzschild's method. Much of the observed qualitative behaviour can be reproduced with a toy potential given as the sum of an anisotropic harmonic oscillator and a spherical Plummer potential, which suggests that the results may be generic.Comment: 18 pages, including 19 figures; Accepted for publication by MNRAS; higher quality figures available from http://www.astro.ufl.edu/~siopis/papers

Chaos and the continuum limit in the gravitational N-body problem II. Nonintegrable potentials

This paper continues a numerical investigation of orbits evolved in `frozen,' time-independent N-body realisations of smooth time-independent density distributions corresponding to both integrable and nonintegrable potentials, allowing for N as large as 300,000. The principal focus is on distinguishing between, and quantifying, the effects of graininess on initial conditions corresponding, in the continuum limit, to regular and chaotic orbits. Ordinary Lyapunov exponents X do not provide a useful diagnostic for distinguishing between regular and chaotic behaviour. Frozen-N orbits corresponding in the continuum limit to both regular and chaotic characteristics have large positive X even though, for large N, the `regular' frozen-N orbits closely resemble regular characteristics in the smooth potential. Viewed macroscopically both `regular' and `chaotic' frozen-N orbits diverge as a power law in time from smooth orbits with the same initial condition. There is, however, an important difference between `regular' and `chaotic' frozen-N orbits: For regular orbits, the time scale associated with this divergence t_G ~ N^{1/2}t_D, with t_D a characteristic dynamical time; for chaotic orbits t_G ~ (ln N) t_D. At least for N>1000 or so, clear distinctions exist between phase mixing of initially localised orbit ensembles which, in the continuum limit, exhibit regular versus chaotic behaviour. For both regular and chaotic ensembles, finite-N effects are well mimicked, both qualitatively and quantitatively, by energy-conserving white noise with amplitude ~ 1/N. This suggests strongly that earlier investigations of the effects of low amplitude noise on phase space transport in smooth potentials are directly relevant to real physical systems.Comment: 20 pages, including 21 FIGURES, uses RevTeX macro

Regulation of cell survival by sphingosine-1-phosphate receptor S1P1 via reciprocal ERK-dependent suppression of bim and PI-3-kinase/protein kinase C-mediated upregulation of Mcl-1

Although the ability of bioactive lipid sphingosine-1-phosphate (S1P) to positively regulate anti-apoptotic/pro-survival responses by binding to S1P1 is well known, the molecular mechanisms remain unclear. Here we demonstrate that expression of S1P1 renders CCL39 lung fibroblasts resistant to apoptosis following growth factor withdrawal. Resistance to apoptosis was associated with attenuated accumulation of pro-apoptotic BH3-only protein Bim. However, although blockade of extracellular signal-regulated kinase (ERK) activation could reverse S1P1-mediated suppression of Bim accumulation, inhibition of caspase-3 cleavage was unaffected. Instead S1P1-mediated inhibition of caspase-3 cleavage was reversed by inhibition of phosphatidylinositol-3-kinase (PI3K) and protein kinase C (PKC), which had no effect on S1P1 regulation of Bim. However, S1P1 suppression of caspase-3 was associated with increased expression of anti-apoptotic protein Mcl-1, the expression of which was also reduced by inhibition of PI3K and PKC. A role for the induction of Mcl-1 in regulating endogenous S1P receptor-dependent pro-survival responses in human umbilical vein endothelial cells was confirmed using S1P receptor agonist FTY720-phosphate (FTY720P). FTY720P induced a transient accumulation of Mcl-1 that was associated with a delayed onset of caspase-3 cleavage following growth factor withdrawal, whereas Mcl-1 knockdown was sufficient to enhance caspase-3 cleavage even in the presence of FTY720P. Consistent with a pro-survival role of S1P1 in disease, analysis of tissue microarrays from ER+ breast cancer patients revealed a significant correlation between S1P1 expression and tumour cell survival. In these tumours, S1P1 expression and cancer cell survival were correlated with increased activation of ERK, but not the PI3K/PKB pathway. In summary, pro-survival/anti-apoptotic signalling from S1P1 is intimately linked to its ability to promote the accumulation of pro-survival protein Mcl-1 and downregulation of pro-apoptotic BH3-only protein Bim via distinct signalling pathways. However, the functional importance of each pathway is dependent on the specific cellular context