Dynamical effects induced by long range activation in a nonequilibrium reaction-diffusion system

We both show experimentally and numerically that the time scales separation introduced by long range activation can induce oscillations and excitability in nonequilibrium reaction-diffusion systems that would otherwise only exhibit bistability. Namely, we show that the Chlorite-Tetrathionate reaction, where autocatalytic species diffuses faster than the substrates, the spatial bistability domain in the nonequilibrium phase diagram is extended with oscillatory and excitability domains. A simple model and a more realistic model qualitatively account for the observed behavior. The latter model provides quantitative agreement with the experiments.Comment: 19 pages + 9 figure

Quantitative measures of health policy implementation determinants and outcomes: A systematic review

BACKGROUND: Public policy has tremendous impacts on population health. While policy development has been extensively studied, policy implementation research is newer and relies largely on qualitative methods. Quantitative measures are needed to disentangle differential impacts of policy implementation determinants (i.e., barriers and facilitators) and outcomes to ensure intended benefits are realized. Implementation outcomes include acceptability, adoption, appropriateness, compliance/fidelity, feasibility, penetration, sustainability, and costs. This systematic review identified quantitative measures that are used to assess health policy implementation determinants and outcomes and evaluated the quality of these measures. METHODS: Three frameworks guided the review: Implementation Outcomes Framework (Proctor et al.), Consolidated Framework for Implementation Research (Damschroder et al.), and Policy Implementation Determinants Framework (Bullock et al.). Six databases were searched: Medline, CINAHL Plus, PsycInfo, PAIS, ERIC, and Worldwide Political. Searches were limited to English language, peer-reviewed journal articles published January 1995 to April 2019. Search terms addressed four levels: health, public policy, implementation, and measurement. Empirical studies of public policies addressing physical or behavioral health with quantitative self-report or archival measures of policy implementation with at least two items assessing implementation outcomes or determinants were included. Consensus scoring of the Psychometric and Pragmatic Evidence Rating Scale assessed the quality of measures. RESULTS: Database searches yielded 8417 non-duplicate studies, with 870 (10.3%) undergoing full-text screening, yielding 66 studies. From the included studies, 70 unique measures were identified to quantitatively assess implementation outcomes and/or determinants. Acceptability, feasibility, appropriateness, and compliance were the most commonly measured implementation outcomes. Common determinants in the identified measures were organizational culture, implementation climate, and readiness for implementation, each aspects of the internal setting. Pragmatic quality ranged from adequate to good, with most measures freely available, brief, and at high school reading level. Few psychometric properties were reported. CONCLUSIONS: Well-tested quantitative measures of implementation internal settings were under-utilized in policy studies. Further development and testing of external context measures are warranted. This review is intended to stimulate measure development and high-quality assessment of health policy implementation outcomes and determinants to help practitioners and researchers spread evidence-informed policies to improve population health. REGISTRATION: Not registered

A hepatitis B virus causes chronic infections in equids worldwide

Preclinical testing of novel therapeutics for chronic hepatitis B (CHB) requires suitable animal models. Equids host homologs of hepatitis C virus (HCV). Because coinfections of hepatitis B virus (HBV) and HCV occur in humans, we screened 2,917 specimens from equids from five continents for HBV. We discovered a distinct HBV species (Equid HBV, EqHBV) in 3.2% of donkeys and zebras by PCR and antibodies against EqHBV in 5.4% of donkeys and zebras. Molecular, histopathological, and biochemical analyses revealed that infection patterns of EqHBV resembled those of HBV in humans, including hepatotropism, moderate liver damage, evolutionary stasis, and potential horizontal virus transmission. Naturally infected donkeys showed chronic infections resembling CHB with high viral loads of up to 2.6 × 109 mean copies per milliliter serum for >6 mo and weak antibody responses. Antibodies against Equid HCV were codetected in 26.5% of donkeys seropositive for EqHBV, corroborating susceptibility to both hepatitis viruses. Deltavirus pseudotypes carrying EqHBV surface proteins were unable to infect human cells via the HBV receptor NTCP (Na+/taurocholate cotransporting polypeptide), suggesting alternative viral entry mechanisms. Both HBV and EqHBV deltavirus pseudotypes infected primary horse hepatocytes in vitro, supporting a broad host range for EqHBV among equids and suggesting that horses might be suitable for EqHBV and HBV infections in vivo. Evolutionary analyses suggested that EqHBV originated in Africa several thousand years ago, commensurate with the domestication of donkeys. In sum, EqHBV naturally infects diverse equids and mimics HBV infection patterns. Equids provide a unique opportunity for preclinical testing of novel therapeutics for CHB and to investigate HBV/ HCV interplay upon coinfection

Chromatin and epigenetics: current biophysical views

Recent advances in high-throughput sequencing experiments and their theoretical descriptions have determined fast dynamics of the "chromatin and epigenetics" field, with new concepts appearing at high rate. This field includes but is not limited to the study of DNA-protein-RNA interactions, chromatin packing properties at different scales, regulation of gene expression and protein trafficking in the cell nucleus, binding site search in the crowded chromatin environment and modulation of physical interactions by covalent chemical modifications of the binding partners. The current special issue does not pretend for the full coverage of the field, but it rather aims to capture its development and provide a snapshot of the most recent concepts and approaches. Eighteen open-access articles comprising this issue provide a delicate balance between current theoretical and experimental biophysical approaches to uncover chromatin structure and understand epigenetic regulation, allowing free flow of new ideas and preliminary results

Influence of HAART on Alternative Reading Frame Immune Responses over the Course of HIV-1 Infection

Background: Translational errors can result in bypassing of the main viral protein reading frames and the production of alternate reading frame (ARF) or cryptic peptides. Within HIV, there are many such ARFs in both sense and the antisense directions of transcription. These ARFs have the potential to generate immunogenic peptides called cryptic epitopes (CE). Both antiretroviral drug therapy and the immune system exert a mutational pressure on HIV-1. Immune pressure exerted by ARF CD8(+) T cells on the virus has already been observed in vitro. HAART has also been described to select HIV-1 variants for drug escape mutations. Since the mutational pressure exerted on one location of the HIV-1 genome can potentially affect the 3 reading frames, we hypothesized that ARF responses would be affected by this drug pressure in vivo. Methodology/Principal findings: In this study we identified new ARFs derived from sense and antisense transcription of HIV-1. Many of these ARFs are detectable in circulating viral proteins. They are predominantly found in the HIV-1 env nucleotide region. We measured T cell responses to 199 HIV-1 CE encoded within 13 sense and 34 antisense HIV-1 ARFs. We were able to observe that these ARF responses are more frequent and of greater magnitude in chronically infected individuals compared to acutely infected patients, and in patients on HAART, the breadth of ARF responses increased. Conclusions/Significance: These results have implications for vaccine design and unveil the existence of potential new epitopes that could be included as vaccine targets.International AIDS Vaccine Initiative (IAVI