Using nonequilibrium fluctuation theorems to understand and correct errors in equilibrium and nonequilibrium discrete Langevin dynamics simulations

Common algorithms for computationally simulating Langevin dynamics must discretize the stochastic differential equations of motion. These resulting finite time step integrators necessarily have several practical issues in common: Microscopic reversibility is violated, the sampled stationary distribution differs from the desired equilibrium distribution, and the work accumulated in nonequilibrium simulations is not directly usable in estimators based on nonequilibrium work theorems. Here, we show that even with a time-independent Hamiltonian, finite time step Langevin integrators can be thought of as a driven, nonequilibrium physical process. Once an appropriate work-like quantity is defined -- here called the shadow work -- recently developed nonequilibrium fluctuation theorems can be used to measure or correct for the errors introduced by the use of finite time steps. In particular, we demonstrate that amending estimators based on nonequilibrium work theorems to include this shadow work removes the time step dependent error from estimates of free energies. We also quantify, for the first time, the magnitude of deviations between the sampled stationary distribution and the desired equilibrium distribution for equilibrium Langevin simulations of solvated systems of varying size. While these deviations can be large, they can be eliminated altogether by Metropolization or greatly diminished by small reductions in the time step. Through this connection with driven processes, further developments in nonequilibrium fluctuation theorems can provide additional analytical tools for dealing with errors in finite time step integrators.Comment: 11 pages, 4 figure

Calibration of BVRI Photometry for the Wide Field Channel of the HST Advanced Camera for Surveys

We present new observations of two Galactic globular clusters, PAL4 and PAL14, using the Wide-Field Channel of the Advanced Camera for Surveys (ACS) on board the Hubble Space Telescope (HST), and reanalyze archival data from a third, NGC2419. We matched our photometry of hundreds of stars in these fields from the ACS images to existing, ground-based photometry of faint sequences which were calibrated on the standard BVRI system of Landolt. These stars are significantly fainter than those generally used for HST calibration purposes, and therefore are much better matched to supporting precision photometry of ACS science targets. We were able to derive more accurate photometric transformation coefficients for the commonly used ACS broad-band filters compared to those published by Sirianni, et al. (2005), owing to the use of a factor of several more calibration stars which span a greater range of color. We find that the inferred transformations from each cluster individually do not vary significantly from the average, except for a small offset of the photometric zeropoint in the F850LP filter. Our results suggest that the published prescriptions for the time-dependent correction of CCD charge-transfer efficiency appear to work very well over the ~3.5 yr interval that spans our observations of PAL4 and PAL14 and the archived images of NGC2419.Comment: 22 pages, 12 figures. Accepted for publication in PAS

He 2-104: A link between symbiotic stars and planetary nebulae

Ultraviolet, optical and infrared observations of He 2-104 are presented, and estimates for some of the physical properties of the nebular shell are made. It is argued that He 2-104 is in transition between the D-type symbiotic star and bipolar planetary nebula phases and, as such, represents a link between subclasses of these two types of objects. The model includes a binary system with a Mira variable and a hot, evolved star. Previous mass loss has resulted in the formation of a disk of gas and dust around the whole system, while the hot star has an accretion disk which produces the observed highly ionized emission line spectrum. Emission lines from cooler, lower density gas is also observed to come from the nebula. In addition, matter is flowing out of the system in a direction perpendicular to the disk with a high velocity and is impacting upon the previously-ejected red giant wind and/or the ambient interstellar medium

Silent ischemia: Evaluation by exercise and redistribution tomographic thallium-201 myocardial imaging

AbstractTo compare the amount of myocardium jeopardized during silent ischemia and painful ischemia, 112 consecutive patients undergoing coronary arteriography with ischemia demonstrated by exercise and redistribution tomographic thallium-201 myocardial imaging (SPECT) were divided into two groups: 84 patients without anginal pain (silent ischemia) and 28 with pain (painful ischemia). The SPECT apical, mid and basal ventricular levels of the short-axis view and the apical portion of the long-axis view were divided into 20 segments.The results were 1) 7.4 ± 4.7 ischemic segments in silent ischemia and 7.6 ± 3.7 in painful ischemia (p = NS) with 4.7 ± 3.6 segments in silent ischemia undergoing total redistribution compared with 5.4 ± 3.4 in painful ischemia (p = NS); 2) no difference in the incidence of single, double or triple vessel disease between silent and painful ischemic groups; 3) similar anatomic distribution of ischemic segments between the two groups; 4) more positive exercise electrocardiographic (ECG) changes in painful ischemia (70%) than in silent ischemia (32%) (p < 0.001) with equal amounts of ischemia associated with positive and negative exercise ECG findings.Conclusions: 1) Patients with silent and painful ischemia during exercise have similar amounts of ischemic myocardium demonstrated by tomographic thallium-201 imaging and similar extent of angiographically documented coronary artery disease despite the absence of pain and the lower incidence of positive exercise ECG findings in silent ischemia. 2) Positive and negative exercise ECG findings were associated with similar amounts of ischemic myocardium

Fundamental properties of the mammalian innate immune system revealed by multispecies comparison of type I interferon responses

The host innate immune response mediated by type I interferon (IFN) and the resulting up-regulation of hundreds of interferon-stimulated genes (ISGs) provide an immediate barrier to virus infection. Studies of the type I ‘interferome’ have mainly been carried out at a single species level, often lacking the power necessary to understand key evolutionary features of this pathway. Here, using a single experimental platform, we determined the properties of the interferomes of multiple vertebrate species and developed a webserver to mine the dataset. This approach revealed a conserved ‘core’ of 62 ISGs, including genes not previously associated with IFN, underscoring the ancestral functions associated with this antiviral host response. We show that gene expansion contributes to the evolution of the IFN system and that interferomes are shaped by lineage-specific pressures. Consequently, each mammal possesses a unique repertoire of ISGs, including genes common to all mammals and others unique to their specific species or phylogenetic lineages. An analysis of genes commonly down-regulated by IFN suggests that epigenetic regulation of transcription is a fundamental aspect of the IFN response. Our study provides a resource for the scientific community highlighting key paradigms of the type I IFN response

Predonation Health-Related Quality of Life Scores Predict Time to Recovery in Hematopoietic Stem Cell Donors

AbstractThe physical reactions to hematopoietic stem cell donation have been extensively studied, but less is known about factors that predict poorer donation experiences. The aim of this prospective study was to examine demographic and health-related quality of life (HRQOL) factors that might be associated with recovery and side effects. We also described the changes in HRQOL during the donation process. In total, 275 peripheral blood stem cell (PBSC) and 37 bone marrow (BM) consecutive donors completed the SF-36 questionnaire predonation and 4 weeks, and 3 months postdonation. Predonation HRQOL markers were the strongest predictors of time to recovery. Poorer predonation physical health was associated with longer recovery (P = .017) and certain side effects in PBSC donors. Poorer predonation mental health was associated with longer recovery in BM donors (P = .03) and pain after PBSC donation (P = .003). Physical HRQOL scores declined significantly from predonation to 4 weeks postdonation. This was shown both for PBSC and BM donors (P < .001 and P = .009, respectively), but the decline was much greater for BM donors. There was a return to predonation HRQOL values 3 months after donation in both groups with values well above the mean of the general population (P < .001)

The reflexive imperative in the digital age:Using Archer’s ‘fractured reflexivity’ to theorise widening inequities in UK general practice

‘Reflexivity’, as used by Margaret Archer, means creative self-mastery that enables individuals to evaluate their social situation and act purposively within it. People with complex health and social needs may be less able to reflect on their predicament and act to address it. Reflexivity is imperative in complex and changing social situations. The substantial widening of health inequities since the introduction of remote and digital modalities in health care has been well-documented but inadequately theorised. In this article, we use Archer’s theory of fractured reflexivity to understand digital disparities in data from a 28-month longitudinal ethnographic study of 12 UK general practices and a sample of in-depth clinical cases from ‘Deep End’ practices serving highly deprived populations. Through four composite patient cases crafted to illustrate different dimensions of disadvantage, we show how adverse past experiences and structural inequities intersect with patients’ reflexive capacity to self-advocate and act strategically. In some cases, staff were able to use creative workarounds to compensate for patients’ fractured reflexivity, but such actions were limited by workforce capacity and staff awareness. Unless a more systematic safety net is introduced and resourced, people with complex needs are likely to remain multiply disadvantaged by remote and digital health care