Which Distributions (or Families of Distributions) Best Represent Interval Uncertainty: Case of Permutation-Invariant Criteria

In many practical situations, we only know the interval containing the quantity of interest, we have no information about the probability of different values within this interval. In contrast to the cases when we know the distributions and can thus use Monte-Carlo simulations, processing such interval uncertainty is difficult -- crudely speaking, because we need to try all possible distributions on this interval. Sometimes, the problem can be simplified: namely, it is possible to select a single distribution (or a small family of distributions) whose analysis provides a good understanding of the situation. The most known case is when we use the Maximum Entropy approach and get the uniform distribution on the interval. Interesting, sensitivity analysis -- which has completely different objectives -- leads to selection of the same uniform distribution. In this paper, we provide a general explanation of why uniform distribution appears in different situations -- namely, it appears every time we have a permutation-invariant objective functions with the unique optimum. We also discuss what happens if there are several optima

Magnetic domain texture and the Dzyaloshinskii-Moriya interaction in Pt/Co/IrMn and Pt/Co/FeMn thin films with perpendicular exchange bias

Antiferromagnetic materials present us with rich and exciting physics, which we can exploit to open new avenues in spintronic device applications. We explore perpendicularly magnetized exchange biased systems of Pt/Co/IrMn and Pt/Co/FeMn, where the crossover from paramagnetic to antiferromagnetic behavior in the IrMn and FeMn layers is accessed by varying the thickness. We demonstrate, through magneto-optical imaging, that the magnetic domain morphology of the ferromagnetic Co layer is influenced by the Néel order of the antiferromagnet (AFM) layers. We relate these variations to the anisotropy energy of the AFM layer and the ferromagnet-antiferromagnet (FM-AFM) interlayer exchange coupling. We also quantify the interfacial Dzyaloshinskii-Moriya interaction (DMI) in these systems by Brillouin light scattering spectroscopy. The DMI remains unchanged, within experimental uncertainty, for different phases of the AFM layers, which allows us to conclude that the DMI is largely insensitive to both AFM layer spin order and exchange bias. Understanding such fundamental mechanisms is crucial for the development of future devices employing chiral spin textures, such as Néel domain walls and skyrmions, in FM-AFM heterostructures

A Survey on Continuous Time Computations

We provide an overview of theories of continuous time computation. These theories allow us to understand both the hardness of questions related to continuous time dynamical systems and the computational power of continuous time analog models. We survey the existing models, summarizing results, and point to relevant references in the literature

Output from VIP cells of the mammalian central clock regulates daily physiological rhythms

The suprachiasmatic nucleus (SCN) circadian clock is critical for optimising daily cycles in mammalian physiology and behaviour. The roles of the various SCN cell types in communicating timing information to downstream physiological systems remain incompletely understood, however. In particular, while vasoactive intestinal polypeptide (VIP) signalling is essential for SCN function and whole animal circadian rhythmicity, the specific contributions of VIP cell output to physiological control remains uncertain. Here we reveal a key role for SCN VIP cells in central clock output. Using multielectrode recording and optogenetic manipulations, we show that VIP neurons provide coordinated daily waves of GABAergic input to target cells across the paraventricular hypothalamus and ventral thalamus, supressing their activity during the mid to late day. Using chemogenetic manipulation, we further demonstrate specific roles for this circuitry in the daily control of heart rate and corticosterone secretion, collectively establishing SCN VIP cells as influential regulators of physiological timing

Domain-wall motion and interfacial Dzyaloshinskii-Moriya interactions in Pt/Co/Ir(tIr)/Ta multilayers

The interfacial Dzyaloshinskii-Moriya interaction (DMI) is important for chiral domain walls (DWs) and for stabilizing magnetic skyrmions. We study the effects of introducing increasing thicknesses of Ir, from zero to 2 nm, into a Pt/Co/Ta multilayer between the Co and Ta layers. There is a marked increase in magnetic moment, due to the suppression of the dead layer at the interface with Ta, but the perpendicular anisotropy is hardly affected. All samples show a universal scaling of the field-driven DW velocity across the creep and depinning regimes. Asymmetric bubble expansion shows that DWs in all of the samples have the left-handed Néel form. The value of in-plane magnetic field at which the creep velocity shows a minimum drops markedly on the introduction of Ir, as does the frequency shift of the Stokes and anti-Stokes peaks in Brillouin light scattering (BLS) measurements. Despite this qualitative similarity, there are quantitative differences in the DMI strength given by the two measurements, with BLS often returning higher values. Many features in bubble expansion velocity curves do not fit simple models commonly used, namely a lack of symmetry about the velocity minimum and no difference in velocities at high in-plane fields. These features are explained by the use of a new model in which the depinning field is allowed to vary with in-plane field in a way determined from micromagnetic simulations. This theory shows that the velocity minimum underestimates the DMI field, consistent with BLS giving higher values. Our results suggest that the DMI at an Ir/Co interface has the same sign as the DMI at a Pt/Co interface

Double-Stranded RNA Attenuates the Barrier Function of Human Pulmonary Artery Endothelial Cells

Circulating RNA may result from excessive cell damage or acute viral infection and can interact with vascular endothelial cells. Despite the obvious clinical implications associated with the presence of circulating RNA, its pathological effects on endothelial cells and the governing molecular mechanisms are still not fully elucidated. We analyzed the effects of double stranded RNA on primary human pulmonary artery endothelial cells (hPAECs). The effect of natural and synthetic double-stranded RNA (dsRNA) on hPAECs was investigated using trans-endothelial electric resistance, molecule trafficking, calcium (Ca2+) homeostasis, gene expression and proliferation studies. Furthermore, the morphology and mechanical changes of the cells caused by synthetic dsRNA was followed by in-situ atomic force microscopy, by vascular-endothelial cadherin and F-actin staining. Our results indicated that exposure of hPAECs to synthetic dsRNA led to functional deficits. This was reflected by morphological and mechanical changes and an increase in the permeability of the endothelial monolayer. hPAECs treated with synthetic dsRNA accumulated in the G1 phase of the cell cycle. Additionally, the proliferation rate of the cells in the presence of synthetic dsRNA was significantly decreased. Furthermore, we found that natural and synthetic dsRNA modulated Ca2+ signaling in hPAECs by inhibiting the sarco-endoplasmic Ca2+-ATPase (SERCA) which is involved in the regulation of the intracellular Ca2+ homeostasis and thus cell growth. Even upon synthetic dsRNA stimulation silencing of SERCA3 preserved the endothelial monolayer integrity. Our data identify novel mechanisms by which dsRNA can disrupt endothelial barrier function and these may be relevant in inflammatory processes

Circulating microRNAs Reveal Time Course of Organ Injury in a Porcine Model of Acetaminophen-Induced Acute Liver Failure

Acute liver failure is a rare but catastrophic condition which can progress rapidly to multi-organ failure. Studies investigating the onset of individual organ injury such as the liver, kidneys and brain during the evolution of acute liver failure, are lacking. MicroRNAs are short, non-coding strands of RNA that are released into the circulation following tissue injury. In this study, we have characterised the release of both global microRNA and specific microRNA species into the plasma using a porcine model of acetaminophen-induced acute liver failure. Pigs were induced to acute liver failure with oral acetaminophen over 19h±2h and death occurred 13h±3h thereafter. Global microRNA concentrations increased 4h prior to acute liver failure in plasma (P<0.0001) but not in isolated exosomes, and were associated with increasing plasma levels of the damage-associated molecular pattern molecule, genomic DNA (P<0.0001). MiR122 increased around the time of onset of acute liver failure (P<0.0001) and was associated with increasing international normalised ratio (P<0.0001). MiR192 increased 8h after acute liver failure (P<0.0001) and was associated with increasing creatinine (P<0.0001). The increase in miR124-1 occurred concurrent with the pre-terminal increase in intracranial pressure (P<0.0001) and was associated with decreasing cerebral perfusion pressure (P<0.002)

Does clinical method mask significant VTE-related mortality and morbidity in malignant disease?

After more than 150 years of a recognised link between cancer and vascular thromboembolic events (VTE), and despite a greatly improved understanding of its pathophysiology, epidemiology and treatment, the management of patients with cancer and VTE is still limited. Limitations can be related to the thromboembolism itself, the underlying cancer, or to the management process. There is significant literature that deals with the first two, but very little regarding the systems we use, or how the inadequacies in documentation, identification and classification of VTE affect the cancer patients themselves. This review aims to raise awareness of this neglected area and stimulate research that may lead to improvements in patient care

A Danish population-based cohort study of newly diagnosed asthmatic children's care pathway – adherence to guidelines

<p>Abstract</p> <p>Background</p> <p>Asthma is the most common chronic disease in childhood. Large variations exist concerning the number of children being treated by general practitioners and by specialists. Consequently, health related costs due to this disease vary as care by specialists is more expensive compared with care by general practitioners. Little is known of the consequences of these variations concerning the quality of care. The aim of the study was to analyse associations between care providers and adherence to guidelines concerning frequency of contacts with the health service due to asthma.</p> <p>Methods</p> <p>A cohort study was performed of 36,940 incident asthmatic children's (aged 6–14) contacts with the health service using the unique personal registration number to link data from five national registries. The prevalence ratios were calculated for associations between provider (general practitioner, primary care specialist, hospital specialist or both GP and specialist) and adherence with guidelines concerning three indicators of quality of care pathway: 1) diagnostic examination of lung function at start of medical treatment 2) follow-up the first six months and 3) follow-up the next six months. The associations were adjusted for sex, age, socioeconomic status, county, and severity of disease.</p> <p>Results</p> <p>Most children (70.3%) had only been seen by their GP. About 80% of the children were treated with inhaled steroids, 70% were treated with inhaled steroids as well as inhaled beta2agonists and 13% were treated with inhaled beta2agonists only. A total of 12,650 children (34.2%) had no registered asthma-related contacts with the health service except when redeeming prescriptions. Care was in accordance with guidelines in all three indicators of quality in 7% of the cases (GPs only: 3%, primary care specialists only: 16%, hospital specialists: 28%, and both GP and specialists: 13%). Primary care specialists had a 5.01, hospital specialists a 8.81 and both GP and specialists a 4.32 times higher propensity to provide a clinical pathway according to guidelines compared to GPs alone.</p> <p>Conclusion</p> <p>The majority of the children were seen in general practice. Hospital specialists provided care in accordance with guidelines nine times more often compared with GPs, but still only one quarter of these children had pathways in accordance with guidelines. It is relevant to study further if these lacks of adherence to guidelines have implications for the asthmatic children or if guidelines are too demanding concerning frequency of follow-up or if asthmatic children should be stratified to different care pathways.</p

Optimization hardness as transient chaos in an analog approach to constraint satisfaction

Boolean satisfiability [1] (k-SAT) is one of the most studied optimization problems, as an efficient (that is, polynomial-time) solution to k-SAT (for $k\geq 3$) implies efficient solutions to a large number of hard optimization problems [2,3]. Here we propose a mapping of k-SAT into a deterministic continuous-time dynamical system with a unique correspondence between its attractors and the k-SAT solution clusters. We show that beyond a constraint density threshold, the analog trajectories become transiently chaotic [4-7], and the boundaries between the basins of attraction [8] of the solution clusters become fractal [7-9], signaling the appearance of optimization hardness [10]. Analytical arguments and simulations indicate that the system always finds solutions for satisfiable formulae even in the frozen regimes of random 3-SAT [11] and of locked occupation problems [12] (considered among the hardest algorithmic benchmarks); a property partly due to the system's hyperbolic [4,13] character. The system finds solutions in polynomial continuous-time, however, at the expense of exponential fluctuations in its energy function.Comment: 27 pages, 14 figure