The Analyticity of a Generalized Ruelle's Operator

In this work we propose a generalization of the concept of Ruelle operator for one dimensional lattices used in thermodynamic formalism and ergodic optimization, which we call generalized Ruelle operator, that generalizes both the Ruelle operator proposed in [BCLMS] and the Perron Frobenius operator defined in [Bowen]. We suppose the alphabet is given by a compact metric space, and consider a general a-priori measure to define the operator. We also consider the case where the set of symbols that can follow a given symbol of the alphabet depends on such symbol, which is an extension of the original concept of transition matrices from the theory of subshifts of finite type. We prove the analyticity of the Ruelle operator and present some examples

Weighted composition operators on the Dirichlet space: boundedness and spectral properties

Boundedness of weighted composition operators W u,φ acting on the classical Dirichlet space D as W u,φ f=u(f∘φ) is studied in terms of the multiplier space associated to the symbol φ , i.e., M(φ)={u∈D:W u,φ is bounded on D} . A prominent role is played by the multipliers of the Dirichlet space. As a consequence, the spectrum of W u,φ in D whenever φ is an automorphism of the unit disc is studied, extending a recent work of Hyvärinen et al. (J. Funct. Anal. 265:1749–1777, 2013) to the context of the Dirichlet space

β-Adrenoceptor blockade modulates fusiform gyrus activity to black versus white faces.

INTRODUCTION: The beta-adrenoceptor antagonist propranolol is known to reduce peripheral and central activity of noradrenaline. A recent study found that intervention with propranolol diminished negative implicit racial bias. MATERIALS AND METHOD: The current study used functional magnetic resonance imaging (fMRI) in order to determine the neural correlates of this effect. Healthy volunteers (N = 40) of white ethnic origin received a single oral dose (40 mg) of propranolol, in a randomised, double-blind, parallel group, placebo-controlled design, before viewing unfamiliar faces of same and other race. RESULTS AND DISCUSSION: We found significantly reduced activity in the fusiform gyrus and thalamus following propranolol to out-group faces only. Additionally, propranolol lowered the implicit attitude score, without affecting explicit prejudice measure. CONCLUSION: These findings suggest that noradrenaline pathways might modulate racial bias by acting on the processing of categorisation in the fusiform gyrus

International Variation in Severe Exacerbation Rates in Patients With Severe Asthma.

BACKGROUND: Exacerbation frequency strongly influences treatment choices in patients with severe asthma. RESEARCH QUESTION: What is the extent of the variability of exacerbations rate across countries and its implications in disease management? STUDY DESIGN AND METHODS: We retrieved data from the International Severe Asthma Registry, an international observational cohort of patients with a clinical diagnosis of severe asthma. We identified patients ≥ 18 years of age who did not initiate any biologics prior to baseline visit. A severe exacerbation was defined as the use of oral corticosteroids for ≥ 3 days or asthma-related hospitalization/ED visit. A series of negative binomial models were applied to estimate country-specific severe exacerbation rates during 365 days of follow-up, starting from a naïve model with country as the only variable to an adjusted model with country as a random-effect term and patient and disease characteristics as independent variables. RESULTS: The final sample included 7,510 patients from 17 countries (56% from the United States), contributing to 1,939 severe exacerbations (0.27/person-year). There was large between-country variation in observed severe exacerbation rate (minimum, 0.04 [Argentina]; maximum, 0.88 [Saudi Arabia]; interquartile range, 0.13-0.54), which remained substantial after adjusting for patient characteristics and sampling variability (interquartile range, 0.16-0.39). INTERPRETATION: Individuals with similar patient characteristics but coming from different jurisdictions have varied severe exacerbation risks, even after controlling for patient and disease characteristics. This suggests unknown patient factors or system-level variations at play. Disease management guidelines should recognize such between-country variability. Risk prediction models that are calibrated for each jurisdiction will be needed to optimize treatment strategies

Excess maternal salt intake produces sex-specific hypertension in offspring: putative roles for kidney and gastrointestinal sodium handling.

Hypertension is common and contributes, via cardiovascular disease, towards a large proportion of adult deaths in the Western World. High salt intake leads to high blood pressure, even when occurring prior to birth - a mechanism purported to reside in altered kidney development and later function. Using a combination of in vitro and in vivo approaches we tested whether increased maternal salt intake influences fetal kidney development to render the adult individual more susceptible to salt retention and hypertension. We found that salt-loaded pregnant rat dams were hypernatraemic at day 20 gestation (147±5 vs. 128±5 mmoles/L). Increased extracellular salt impeded murine kidney development in vitro, but had little effect in vivo. Kidneys of the adult offspring had few structural or functional abnormalities, but male and female offspring were hypernatraemic (166±4 vs. 149±2 mmoles/L), with a marked increase in plasma corticosterone (e.g. male offspring; 11.9 [9.3-14.8] vs. 2.8 [2.0-8.3] nmol/L median [IQR]). Furthermore, adult male, but not female, offspring had higher mean arterial blood pressure (effect size, +16 [9-21] mm Hg; mean [95% C.I.]. With no clear indication that the kidneys of salt-exposed offspring retained more sodium per se, we conducted a preliminary investigation of their gastrointestinal electrolyte handling and found increased expression of proximal colon solute carrier family 9 (sodium/hydrogen exchanger), member 3 (SLC9A3) together with altered faecal characteristics and electrolyte handling, relative to control offspring. On the basis of these data we suggest that excess salt exposure, via maternal diet, at a vulnerable period of brain and gut development in the rat neonate lays the foundation for sustained increases in blood pressure later in life. Hence, our evidence further supports the argument that excess dietary salt should be avoided per se, particularly in the range of foods consumed by physiologically immature young

The epidemiology and management of severe hypertension

Hypertension guidelines stress that patients with severe hypertension (systolic blood pressure (BP)⩾180 or diastolic BP⩾110 mm Hg) require multiple drugs to achieve control and should have close follow-up to prevent adverse outcomes. However, little is known about the epidemiology or actual management of these patients. We retrospectively studied 59 207 veterans with hypertension. Patients were categorized based on their highest average BP over an 18-month period (1 July 1999 to 31 December 2000) as controlled (<140/90 mm Hg), mild (140–159/90–99 mm Hg), moderate (160–179/100–109 mm Hg) and severe hypertension. We examined severe hypertension prevalence, pattern, duration, associated patient characteristics, time to subsequent visit, percentage of visits with a medication increase, and final BP control and antihypertensive medication adequacy. Twenty-three per cent had ⩾1 visit with severe hypertension, 42% of whom had at least two such visits; median day with severe hypertension was 80 (range 1–548). These subjects were significantly older, more likely black, and with more comorbidities than other hypertension subjects. Medication increases occurred at 20% of visits with mild hypertension compared to 40% with severe hypertension; P<0.05). At study end, 76% of patients with severe hypertension remained uncontrolled; severe hypertension subjects with uncontrolled BP were less likely to be on adequate therapy than those with controlled BP (43.7 vs 45.4%). Among hypertensive veterans, severe hypertension episodes are common. Many subjects had relatively prolonged elevations, with older, sicker subjects at highest risk. Although, follow-up times are shorter and antihypertensive medication use greater in severe hypertension subjects, they are still not being managed aggressively enough. Interventions to improve providers' management of these high-risk patients are needed

Activity of cortical and thalamic neurons during the slow (<1 Hz) rhythm in the mouse in vivo

During NREM sleep and under certain types of anaesthesia, the mammalian brain exhibits a distinctive slow (<1 Hz) rhythm. At the cellular level, this rhythm correlates with so-called UP and DOWN membrane potential states. In the neocortex, these UP and DOWN states correspond to periods of intense network activity and widespread neuronal silence, respectively, whereas in thalamocortical (TC) neurons, UP/DOWN states take on a more stereotypical oscillatory form, with UP states commencing with a low-threshold Ca2+ potential (LTCP). Whilst these properties are now well recognised for neurons in cats and rats, whether or not they are also shared by neurons in the mouse is not fully known. To address this issue, we obtained intracellular recordings from neocortical and TC neurons during the slow (<1 Hz) rhythm in anaesthetised mice. We show that UP/DOWN states in this species are broadly similar to those observed in cats and rats, with UP states in neocortical neurons being characterised by a combination of action potential output and intense synaptic activity, whereas UP states in TC neurons always commence with an LTCP. In some neocortical and TC neurons, we observed ‘spikelets’ during UP states, supporting the possible presence of electrical coupling. Lastly, we show that, upon tonic depolarisation, UP/DOWN states in TC neurons are replaced by rhythmic high-threshold bursting at ~5 Hz, as predicted by in vitro studies. Thus, UP/DOWN state generation appears to be an elemental and conserved process in mammals that underlies the slow (<1 Hz) rhythm in several species, including humans

Characterization of MgtC, a Virulence Factor of Salmonella enterica Serovar Typhi

The MgtC is a virulence factor in Salmonella Typhimurium that is required for growth at low-Mg2+ concentrations and intramacrophage survival. This gene is codified in a conserved region of the Salmonella pathogenicity island 3 (SPI-3), and is also present in the chromosome of other Salmonella serovars. In this study we characterized the MgtC factor in S. Typhi, a human specific pathogen, by using mgtC and SPI-3 mutant strains. We found that MgtC is the most important factor codified in the SPI-3 of S. Typhi for growth in low-Mg2+ media and survival within human cells. In addition, by using reporter genes we determined that the low-Mg2+ concentration, acidic media and PhoP regulator induce mgtC expression in S. Typhi. We suggest that MgtC is the most important virulence factor codified in the SPI-3 of S. Typhi

Transcriptional Analysis of Distant Signaling Induced by Insect Elicitors and Mechanical Wounding in Zea mays

When plants are under insect herbivore attack defensive measures are activated not only locally, but also in distant and systemic tissues. While insect elicitors (IE) abundant in the oral secretions of the attacking herbivore are essential in the regulation of induced defenses, little is known about their effects on systemic defense signaling in maize (Zea mays). The goal of this study was therefore to identify genetic markers that can be used to further characterize local and systemic signaling events induced by IE or mechanical wounding (MW). We selected genes for this study based on their putative involvement in signaling (allene oxide synthase), regulation of gene expression (transcription factor MYC7), and in direct defenses (ribosome inactivating protein) and analyzed their expression in different sections of the treated leaf as well as in systemic parts of the same plant. We found the most significant transcript accumulation of the selected genes after treatment with insect elicitors in those parts with increased JA levels. Additionally, treatment with IE did also induce the accumulation of MYC7 transcripts in basal parts of the treated leaf and systemically. MW, in contrast, did induce RIP and AOS only locally, but not MYC7. This local suppression of MYC7 was further studied by adding glutathione (GSH) as an electron donor to MW plants to quench putative α, β-unsaturated carbonyls, which build up to significant levels around the damage site. Indeed, GSH-treated MW plants accumulated MYC7 at the damage site and also produced more volatiles, suggesting a putative redox-regulatory element being involved in the suppression of MYC7. The results presented herein provide evidence for the specific induction of distant signaling events triggered by IE, most likely through electric signaling. Additionally, a putative role for MW-induced α, β-unsaturated carbonyls in the transcriptional regulation of defense genes was discovered