211 research outputs found
Distinct cell shapes determine accurate chemotaxis
Biological and Soft Matter Physic
Noise Filtering Strategies of Adaptive Signaling Networks: The Case of E. Coli Chemotaxis
Two distinct mechanisms for filtering noise in an input signal are identified
in a class of adaptive sensory networks. We find that the high frequency noise
is filtered by the output degradation process through time-averaging; while the
low frequency noise is damped by adaptation through negative feedback. Both
filtering processes themselves introduce intrinsic noises, which are found to
be unfiltered and can thus amount to a significant internal noise floor even
without signaling. These results are applied to E. coli chemotaxis. We show
unambiguously that the molecular mechanism for the Berg-Purcell time-averaging
scheme is the dephosphorylation of the response regulator CheY-P, not the
receptor adaptation process as previously suggested. The high frequency noise
due to the stochastic ligand binding-unbinding events and the random ligand
molecule diffusion is averaged by the CheY-P dephosphorylation process to a
negligible level in E.coli. We identify a previously unstudied noise source
caused by the random motion of the cell in a ligand gradient. We show that this
random walk induced signal noise has a divergent low frequency component, which
is only rendered finite by the receptor adaptation process. For gradients
within the E. coli sensing range, this dominant external noise can be
comparable to the significant intrinsic noise in the system. The dependence of
the response and its fluctuations on the key time scales of the system are
studied systematically. We show that the chemotaxis pathway may have evolved to
optimize gradient sensing, strong response, and noise control in different time
scalesComment: 15 pages, 4 figure
Rate-equation calculations of the current flow through two-site molecular device and DNA-based junction
Here we present the calculations of incoherent current flowing through the
two-site molecular device as well as the DNA-based junction within the
rate-equation approach. Few interesting phenomena are discussed in detail.
Structural asymmetry of two-site molecule results in rectification effect,
which can be neutralized by asymmetric voltage drop at the molecule-metal
contacts due to coupling asymmetry. The results received for poly(dG)-poly(dC)
DNA molecule reveal the coupling- and temperature-independent saturation effect
of the current at high voltages, where for short chains we establish the
inverse square distance dependence. Besides, we document the shift of the
conductance peak in the direction to higher voltages due to the temperature
decrease.Comment: 12 pages, 6 figure
Electronic localization at mesoscopic length scales: different definitions of localization and contact effects in a heuristic DNA model
In this work we investigate the electronic transport along model DNA
molecules using an effective tight-binding approach that includes the backbone
on site energies. The localization length and participation number are examined
as a function of system size, energy dependence, and the contact coupling
between the leads and the DNA molecule. On one hand, the transition from an
diffusive regime to a localized regime for short systems is identified,
suggesting the necessity of a further length scale revealing the system borders
sensibility. On the other hand, we show that the lenght localization and
participation number, do not depended of system size and contact coupling in
the thermodynamic limit. Finally we discuss possible length dependent origins
for the large discrepancies among experimental results for the electronic
transport in DNA sample
Tight-binding parameters for charge transfer along DNA
We systematically examine all the tight-binding parameters pertinent to
charge transfer along DNA. The molecular structure of the four DNA bases
(adenine, thymine, cytosine, and guanine) is investigated by using the linear
combination of atomic orbitals method with a recently introduced
parametrization. The HOMO and LUMO wavefunctions and energies of DNA bases are
discussed and then used for calculating the corresponding wavefunctions of the
two B-DNA base-pairs (adenine-thymine and guanine-cytosine). The obtained HOMO
and LUMO energies of the bases are in good agreement with available
experimental values. Our results are then used for estimating the complete set
of charge transfer parameters between neighboring bases and also between
successive base-pairs, considering all possible combinations between them, for
both electrons and holes. The calculated microscopic quantities can be used in
mesoscopic theoretical models of electron or hole transfer along the DNA double
helix, as they provide the necessary parameters for a tight-binding
phenomenological description based on the molecular overlap. We find that
usually the hopping parameters for holes are higher in magnitude compared to
the ones for electrons, which probably indicates that hole transport along DNA
is more favorable than electron transport. Our findings are also compared with
existing calculations from first principles.Comment: 15 pages, 3 figures, 7 table
Primary stroke prevention worldwide : translating evidence into action
Funding Information: The stroke services survey reported in this publication was partly supported by World Stroke Organization and Auckland University of Technology. VLF was partly supported by the grants received from the Health Research Council of New Zealand. MOO was supported by the US National Institutes of Health (SIREN U54 HG007479) under the H3Africa initiative and SIBS Genomics (R01NS107900, R01NS107900-02S1, R01NS115944-01, 3U24HG009780-03S5, and 1R01NS114045-01), Sub-Saharan Africa Conference on Stroke Conference (1R13NS115395-01A1), and Training Africans to Lead and Execute Neurological Trials & Studies (D43TW012030). AGT was supported by the Australian National Health and Medical Research Council. SLG was supported by a National Heart Foundation of Australia Future Leader Fellowship and an Australian National Health and Medical Research Council synergy grant. We thank Anita Arsovska (University Clinic of Neurology, Skopje, North Macedonia), Manoj Bohara (HAMS Hospital, Kathmandu, Nepal), Denis ?erimagi? (Poliklinika Glavi?, Dubrovnik, Croatia), Manuel Correia (Hospital de Santo Ant?nio, Porto, Portugal), Daissy Liliana Mora Cuervo (Hospital Moinhos de Vento, Porto Alegre, Brazil), Anna Cz?onkowska (Institute of Psychiatry and Neurology, Warsaw, Poland), Gloria Ekeng (Stroke Care International, Dartford, UK), Jo?o Sargento-Freitas (Centro Hospitalar e Universit?rio de Coimbra, Coimbra, Portugal), Yuriy Flomin (MC Universal Clinic Oberig, Kyiv, Ukraine), Mehari Gebreyohanns (UT Southwestern Medical Centre, Dallas, TX, USA), Ivete Pillo Gon?alves (Hospital S?o Jos? do Avai, Itaperuna, Brazil), Claiborne Johnston (Dell Medical School, University of Texas, Austin, TX, USA), Kristaps Jurj?ns (P Stradins Clinical University Hospital, Riga, Latvia), Rizwan Kalani (University of Washington, Seattle, WA, USA), Grzegorz Kozera (Medical University of Gda?sk, Gda?sk, Poland), Kursad Kutluk (Dokuz Eylul University, ?zmir, Turkey), Branko Malojcic (University Hospital Centre Zagreb, Zagreb, Croatia), Micha? Maluchnik (Ministry of Health, Warsaw, Poland), Evija Migl?ne (P Stradins Clinical University Hospital, Riga, Latvia), Cassandra Ocampo (University of Botswana, Princess Marina Hospital, Botswana), Louise Shaw (Royal United Hospitals Bath NHS Foundation Trust, Bath, UK), Lekhjung Thapa (Upendra Devkota Memorial-National Institute of Neurological and Allied Sciences, Kathmandu, Nepal), Bogdan Wojtyniak (National Institute of Public Health, Warsaw, Poland), Jie Yang (First Affiliated Hospital of Chengdu Medical College, Chengdu, China), and Tomasz Zdrojewski (Medical University of Gda?sk, Gda?sk, Poland) for their comments on early draft of the manuscript. The views expressed in this article are solely the responsibility of the authors and they do not necessarily reflect the views, decisions, or policies of the institution with which they are affiliated. We thank WSO for funding. The funder had no role in the design, data collection, analysis and interpretation of the study results, writing of the report, or the decision to submit the study results for publication. Funding Information: The stroke services survey reported in this publication was partly supported by World Stroke Organization and Auckland University of Technology. VLF was partly supported by the grants received from the Health Research Council of New Zealand. MOO was supported by the US National Institutes of Health (SIREN U54 HG007479) under the H3Africa initiative and SIBS Genomics (R01NS107900, R01NS107900-02S1, R01NS115944-01, 3U24HG009780-03S5, and 1R01NS114045-01), Sub-Saharan Africa Conference on Stroke Conference (1R13NS115395-01A1), and Training Africans to Lead and Execute Neurological Trials & Studies (D43TW012030). AGT was supported by the Australian National Health and Medical Research Council. SLG was supported by a National Heart Foundation of Australia Future Leader Fellowship and an Australian National Health and Medical Research Council synergy grant. We thank Anita Arsovska (University Clinic of Neurology, Skopje, North Macedonia), Manoj Bohara (HAMS Hospital, Kathmandu, Nepal), Denis Čerimagić (Poliklinika Glavić, Dubrovnik, Croatia), Manuel Correia (Hospital de Santo António, Porto, Portugal), Daissy Liliana Mora Cuervo (Hospital Moinhos de Vento, Porto Alegre, Brazil), Anna Członkowska (Institute of Psychiatry and Neurology, Warsaw, Poland), Gloria Ekeng (Stroke Care International, Dartford, UK), João Sargento-Freitas (Centro Hospitalar e Universitário de Coimbra, Coimbra, Portugal), Yuriy Flomin (MC Universal Clinic Oberig, Kyiv, Ukraine), Mehari Gebreyohanns (UT Southwestern Medical Centre, Dallas, TX, USA), Ivete Pillo Gonçalves (Hospital São José do Avai, Itaperuna, Brazil), Claiborne Johnston (Dell Medical School, University of Texas, Austin, TX, USA), Kristaps Jurjāns (P Stradins Clinical University Hospital, Riga, Latvia), Rizwan Kalani (University of Washington, Seattle, WA, USA), Grzegorz Kozera (Medical University of Gdańsk, Gdańsk, Poland), Kursad Kutluk (Dokuz Eylul University, İzmir, Turkey), Branko Malojcic (University Hospital Centre Zagreb, Zagreb, Croatia), Michał Maluchnik (Ministry of Health, Warsaw, Poland), Evija Miglāne (P Stradins Clinical University Hospital, Riga, Latvia), Cassandra Ocampo (University of Botswana, Princess Marina Hospital, Botswana), Louise Shaw (Royal United Hospitals Bath NHS Foundation Trust, Bath, UK), Lekhjung Thapa (Upendra Devkota Memorial-National Institute of Neurological and Allied Sciences, Kathmandu, Nepal), Bogdan Wojtyniak (National Institute of Public Health, Warsaw, Poland), Jie Yang (First Affiliated Hospital of Chengdu Medical College, Chengdu, China), and Tomasz Zdrojewski (Medical University of Gdańsk, Gdańsk, Poland) for their comments on early draft of the manuscript. The views expressed in this article are solely the responsibility of the authors and they do not necessarily reflect the views, decisions, or policies of the institution with which they are affiliated. We thank WSO for funding. The funder had no role in the design, data collection, analysis and interpretation of the study results, writing of the report, or the decision to submit the study results for publication. Funding Information: VLF declares that the PreventS web app and Stroke Riskometer app are owned and copyrighted by Auckland University of Technology; has received grants from the Brain Research New Zealand Centre of Research Excellence (16/STH/36), Australian National Health and Medical Research Council (NHMRC; APP1182071), and World Stroke Organization (WSO); is an executive committee member of WSO, honorary medical director of Stroke Central New Zealand, and CEO of New Zealand Stroke Education charitable Trust. AGT declares funding from NHMRC (GNT1042600, GNT1122455, GNT1171966, GNT1143155, and GNT1182017), Stroke Foundation Australia (SG1807), and Heart Foundation Australia (VG102282); and board membership of the Stroke Foundation (Australia). SLG is funded by the National Health Foundation of Australia (Future Leader Fellowship 102061) and NHMRC (GNT1182071, GNT1143155, and GNT1128373). RM is supported by the Implementation Research Network in Stroke Care Quality of the European Cooperation in Science and Technology (project CA18118) and by the IRIS-TEPUS project from the inter-excellence inter-cost programme of the Ministry of Education, Youth and Sports of the Czech Republic (project LTC20051). BN declares receiving fees for data management committee work for SOCRATES and THALES trials for AstraZeneca and fees for data management committee work for NAVIGATE-ESUS trial from Bayer. All other authors declare no competing interests. Publisher Copyright: © 2022 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 licenseStroke is the second leading cause of death and the third leading cause of disability worldwide and its burden is increasing rapidly in low-income and middle-income countries, many of which are unable to face the challenges it imposes. In this Health Policy paper on primary stroke prevention, we provide an overview of the current situation regarding primary prevention services, estimate the cost of stroke and stroke prevention, and identify deficiencies in existing guidelines and gaps in primary prevention. We also offer a set of pragmatic solutions for implementation of primary stroke prevention, with an emphasis on the role of governments and population-wide strategies, including task-shifting and sharing and health system re-engineering. Implementation of primary stroke prevention involves patients, health professionals, funders, policy makers, implementation partners, and the entire population along the life course.publishersversionPeer reviewe
Global, regional, and national comparative risk assessment of 79 behavioural, environmental and occupational, and metabolic risks or clusters of risks, 1990-2015: A systematic analysis for the Global Burden of Disease Study 2015
Background: The Global Burden of Diseases, Injuries, and Risk Factors Study 2015 provides an up-to-date synthesis of the evidence for risk factor exposure and the attributable burden of disease. By providing national and subnational assessments spanning the past 25 years, this study can inform debates on the importance of addressing risks in context.
Methods: We used the comparative risk assessment framework developed for previous iterations of the Global Burden of Disease Study to estimate attributable deaths, disability-adjusted life-years (DALYs), and trends in exposure by age group, sex, year, and geography for 79 behavioural, environmental and occupational, and metabolic risks or clusters of risks from 1990 to 2015. This study included 388 risk-outcome pairs that met World Cancer Research Fund-defined criteria for convincing or probable evidence. We extracted relative risk and exposure estimates from randomised controlled trials, cohorts, pooled cohorts, household surveys, census data, satellite data, and other sources. We used statistical models to pool data, adjust for bias, and incorporate covariates. We developed a metric that allows comparisons of exposure across risk factors—the summary exposure value. Using the counterfactual scenario of theoretical minimum risk level, we estimated the portion of deaths and DALYs that could be attributed to a given risk. We decomposed trends in attributable burden into contributions from population growth, population age structure, risk exposure, and risk-deleted cause-specific DALY rates. We characterised risk exposure in relation to a Socio-demographic Index (SDI).
Findings: Between 1990 and 2015, global exposure to unsafe sanitation, household air pollution, childhood underweight, childhood stunting, and smoking each decreased by more than 25%. Global exposure for several occupational risks, high body-mass index (BMI), and drug use increased by more than 25% over the same period. All risks jointly evaluated in 2015 accounted for 57·8% (95% CI 56·6–58·8) of global deaths and 41·2% (39·8–42·8) of DALYs. In 2015, the ten largest contributors to global DALYs among Level 3 risks were high systolic blood pressure (211·8 million [192·7 million to 231·1 million] global DALYs), smoking (148·6 million [134·2 million to 163·1 million]), high fasting plasma glucose (143·1 million [125·1 million to 163·5 million]), high BMI (120·1 million [83·8 million to 158·4 million]), childhood undernutrition (113·3 million [103·9 million to 123·4 million]), ambient particulate matter (103·1 million [90·8 million to 115·1 million]), high total cholesterol (88·7 million [74·6 million to 105·7 million]), household air pollution (85·6 million [66·7 million to 106·1 million]), alcohol use (85·0 million [77·2 million to 93·0 million]), and diets high in sodium (83·0 million [49·3 million to 127·5 million]). From 1990 to 2015, attributable DALYs declined for micronutrient deficiencies, childhood undernutrition, unsafe sanitation and water, and household air pollution; reductions in risk-deleted DALY rates rather than reductions in exposure drove these declines. Rising exposure contributed to notable increases in attributable DALYs from high BMI, high fasting plasma glucose, occupational carcinogens, and drug use. Environmental risks and childhood undernutrition declined steadily with SDI; low physical activity, high BMI, and high fasting plasma glucose increased with SDI. In 119 countries, metabolic risks, such as high BMI and fasting plasma glucose, contributed the most attributable DALYs in 2015. Regionally, smoking still ranked among the leading five risk factors for attributable DALYs in 109 countries; childhood underweight and unsafe sex remained primary drivers of early death and disability in much of sub-Saharan Africa.
Interpretation: Declines in some key environmental risks have contributed to declines in critical infectious diseases. Some risks appear to be invariant to SDI. Increasing risks, including high BMI, high fasting plasma glucose, drug use, and some occupational exposures, contribute to rising burden from some conditions, but also provide opportunities for intervention. Some highly preventable risks, such as smoking, remain major causes of attributable DALYs, even as exposure is declining. Public policy makers need to pay attention to the risks that are increasingly major contributors to global burden.
Funding: Bill & Melinda Gates Foundation
Searches for invisible decays of the Higgs boson in pp collisions at root S=7, 8, and 13 TeV
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