The adenomatous polyposis coli protein unambiguously localizes to microtubule plus ends and is involved in establishing parallel arrays of microtubule bundles in highly polarized epithelial cells

Loss of full-length adenomatous polyposis coli (APC) protein correlates with the development of colon cancers in familial and sporadic cases. In addition to its role in regulating β-catenin levels in the Wnt signaling pathway, the APC protein is implicated in regulating cytoskeletal organization. APC stabilizes microtubules in vivo and in vitro, and this may play a role in cell migration (Näthke, I.S., C.L. Adams, P. Polakis, J.H. Sellin, and W.J. Nelson. 1996. J. Cell Biol. 134:165–179; Mimori-Kiyosue, Y., N. Shiina, and S. Tsukita. 2000. J. Cell Biol. 148:505–517; Zumbrunn, J., K. Inoshita, A.A. Hyman, and I.S. Näthke. 2001. Curr. Biol. 11:44–49) and in the attachment of microtubules to kinetochores during mitosis (Fodde, R., J. Kuipers, C. Rosenberg, R. Smits, M. Kielman, C. Gaspar, J.H. van Es, C. Breukel, J. Wiegant, R.H. Giles, and H. Clevers. 2001. Nat. Cell Biol. 3:433–438; Kaplan, K.B., A. Burds, J.R. Swedlow, S.S. Bekir, P.K. Sorger, and I.S. Näthke. 2001. Nat. Cell Biol. 3:429–432). The localization of endogenous APC protein is complex: actin- and microtubule-dependent pools of APC have been identified in cultured cells (Näthke et al., 1996; Mimori-Kiyosue et al., 2000; Reinacher-Schick, A., and B.M. Gumbiner. 2001. J. Cell Biol. 152:491–502; Rosin-Arbesfeld, R., G. Ihrke, and M. Bienz. 2001. EMBO J. 20:5929–5939). However, the localization of APC in tissues has not been identified at high resolution. Here, we show that in fully polarized epithelial cells from the inner ear, endogenous APC protein associates with the plus ends of microtubules located at the basal plasma membrane. Consistent with a role for APC in supporting the cytoskeletal organization of epithelial cells in vivo, the number of microtubules is significantly reduced in apico-basal arrays of microtubule bundles isolated from mice heterozygous for APC

Functional status in ICU survivors and out of hospital outcomes: a cohort study

OBJECTIVES: Functional status at hospital discharge may be a risk factor for adverse events among survivors of critical illness. We sought to examine the association between functional status at hospital discharge in survivors of critical care and risk of 90-day all-cause mortality after hospital discharge. DESIGN: Single-center retrospective cohort study. SETTING: Academic Medical Center. PATIENTS: Ten thousand three hundred forty-three adults who received critical care from 1997 to 2011 and survived hospitalization. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: The exposure of interest was functional status determined at hospital discharge by a licensed physical therapist and rated based on qualitative categories adapted from the Functional Independence Measure. The main outcome was 90-day post hospital discharge all-cause mortality. A categorical risk-prediction score was derived and validated based on a logistic regression model of the function grades for each assessment. In an adjusted logistic regression model, the lowest quartile of functional status at hospital discharge was associated with an increased odds of 90-day postdischarge mortality compared with patients with independent functional status (odds ratio, 7.63 [95% CI, 3.83-15.22; p < 0.001]). In patients who had at least 7 days of physical therapy treatment prior to hospital discharge (n = 2,293), the adjusted odds of 90-day postdischarge mortality in patients with marked improvement in functional status at discharge was 64% less than patients with no change in functional status (odds ratio, 0.36 [95% CI, 0.24-0.53]; p < 0.001). CONCLUSIONS: Lower functional status at hospital discharge in survivors of critical illness is associated with increased postdischarge mortality. Furthermore, patients whose functional status improves before discharge have decreased odds of postdischarge mortality.L30 TR001257 - NCATS NIH HH

Impact of the sea surface temperature forcing on hindcasts of Madden-Julian Oscillation events using the ECMWF model

This paper explores the sensitivity of hindcasts of the Madden Julian Oscillation (MJO) to the use of different sea surface temperture (SST) products as lower boundary conditions in the European Centre for Medium-range Weather Forecasts (ECMWF) atmospheric model. Three sets of monthly hindcast experiments are conducted, starting from initial conditions from the ERA interim reanalysis. First, as a reference, the atmosphere is forced by the SST used to produce ERA interim. In the second and third experiments, the SST is switched to the OSTIA (Operational Sea Surface Temperature and Sea-Ice Analysis) and the AVHRR-only (Advanced Very High Resolution Radiometer) reanalyses, respectively. Tests on the temporal resolution of the SST show that monthly fields are not optimal, while weekly and daily resolutions provide similar MJO scores. When using either OSTIA or AVHRR, the propagation of the MJO is degraded and the resulting scores are lower than in the reference experiment. Further experiments show that this loss of skill cannot be attributed to either the difference in mean state or temporal variability between the SST products. Additional diagnostics show that the phase relationship between either OSTIA or AVHRR SST and the MJO convection is distorted with respect to satellite observations and the ERA interim reanalysis. This distortion is expected to impact the MJO hindcasts, leading to a relative loss of forecast skill. A realistic representation of ocean–atmosphere interactions is thus needed for MJO hindcasts, but not all SST products – though accurate for other purposes – fulfill this requirement

The role of positronium decoherence in the studies of positron annihilation in matter

A small difference between the energy of the para-positronium (p-Ps) and ortho-positronium (o-Ps) states suggests the possibility of superposition of p-Ps and o-Ps during the formation of positronium (Ps) from pre-Ps terminating its migration in the matter in a void ('free volume'). It is shown that such a superposition decohere in the basis of p-Ps and o-Ps and the decoherence time is estimated. The time scale of the decoherence estimated here motivates respective correction in decomposition of the positron annihilation lifetime spectra. The way of the correction is sketched. The timescale of the decoherence suggests a need of awareness when experimental data from positron annihilation techniques are processed. More generally, the superposited state of Ps should contribute to the evolution theory of positronium in matter.Comment: 15 pages, 6 figure

Matter-positronium interaction: An exact diagonalization study of the He atom - positronium system

The many-body system comprising a He nucleus, three electrons, and a positron has been studied using the exact diagonalization technique. The purpose has been to clarify to which extent the system can be considered as a distinguishable positronium (Ps) atom interacting with a He atom and, thereby, to pave the way to a practical atomistic modeling of Ps states and annihilation in matter. The maximum value of the distance between the positron and the nucleus is constrained and the Ps atom at different distances from the nucleus is identified from the electron and positron densities, as well as from the electron-positron distance and center-of-mass distributions. The polarization of the Ps atom increases as its distance from the nucleus decreases. A depletion of the He electron density, particularly large at low density values, has been observed. The ortho-Ps pick-off annihilation rate calculated as the overlap of the positron and the free He electron densities has to be corrected for the observed depletion, specially at large pores/voids.Comment: 18 pages, 8 figure

Detecting Determinacy in Prolog Programs: 22nd International Conference, ICLP 2006, Seattle, WA, USA, August 17-20, 2006. Proceedings

In program development it is useful to know that a call to a Prolog program will not inadvertently leave a choice-point on the stack. Determinacy inference has been proposed for solving this problem yet the analysis was found to be wanting in that it could not infer determinacy conditions for programs that contained cuts or applied certain tests to select a clause. This paper shows how to remedy these serious deficiencies. It also addresses the problem of identifying those predicates which can be rewritten in a more deterministic fashion. To this end, a radically new form of determinacy inference is introduced, which is founded on ideas in ccp, that is capable of reasoning about the way bindings imposed by a rightmost goal can make a leftmost goal deterministic

Type of atrial fibrillation and clinical outcomes in patients with heart failure and reduced ejection fraction

Background: Atrial fibrillation (AF) is common in heart failure (HF), but the outcome by type of AF is largely unknown. Objectives: This study investigated outcomes related to type of AF (paroxysmal, persistent or permanent, or new onset) in 2 recent large trials in patients with HF with reduced ejection fraction. Methods: The study analyzed patients in the PARADIGM-HF (Prospective comparison of ARNI with ACEI to Determine Impact on Global Mortality and morbidity in Heart Failure) and ATMOSPHERE (Aliskiren Trial to Minimize Outcomes in Patients with Heart Failure) trials. Multivariable Cox regression models were used to estimate hazard ratios (HRs) for outcomes related to AF type. Results: Of 15,415 patients, 5,481 (35.6%) had a history of AF at randomization, and of these, 1,645 (30.0%) had paroxysmal AF. Compared with patients without AF, patients with paroxysmal AF at randomization had a higher risk of the primary composite endpoint of cardiovascular death or HF hospitalization (HR: 1.20; 95% confidence interval [CI]: 1.09 to 1.32; p &#60; 0.001), HF hospitalization (HR: 1.34; 95% CI: 1.19 to 1.51; &#60; 0.001), and stroke (HR: 1.34; 95% CI: 1.02 to 1.76; p = 0.037), whereas the corresponding risks in patients with persistent or permanent AF were not elevated. Neither type of AF was associated with higher mortality. New onset AF was associated with the greatest risk of adverse outcomes: primary endpoint (HR: 2.21; 95% CI: 1.80 to 2.71), HF hospitalization (HR: 2.11; 95% CI: 1.58 to 2.81), stroke (HR: 2.20; 95% CI: 1.25 to 3.88), and all-cause mortality (HR: 2.26; 95% CI: 1.86 to 2.74), all p values &#60; 0.001, compared with patients without AF. Anticoagulants were used less often in patients with paroxysmal (53%) and new onset (16%) AF than in patients with persistent or permanent AF (71%). Conclusions: Among HF patients with a history of AF, those with paroxysmal AF were at greater risk of HF hospitalization and stroke than were patients with persistent or permanent AF, underlining the importance of anticoagulant therapy. New onset AF was associated with increased risk of all outcomes. (Prospective comparison of ARNI with ACEI to Determine Impact on Global Mortality and Morbidity in Heart Failure [PARADIGM-HF]; NCT01035255) (Aliskiren Trial to Minimize Outcomes in Patients with Heart Failure [ATMOSPHERE]; NCT00853658