33 research outputs found

    Strategic research agenda for biomedical imaging

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    This Strategic Research Agenda identifies current challenges and needs in healthcare, illustrates how biomedical imaging and derived data can help to address these, and aims to stimulate dedicated research funding efforts. Medicine is currently moving towards a more tailored, patient-centric approach by providing personalised solutions for the individual patient. Innovation in biomedical imaging plays a key role in this process as it addresses the current needs for individualised prevention, treatment, therapy response monitoring, and image-guided surgery. The use of non-invasive biomarkers facilitates better therapy prediction and monitoring, leading to improved patient outcomes. Innovative diagnostic imaging technologies provide information about disease characteristics which, coupled with biological, genetic and -omics data, will contribute to an individualised diagnosis and therapy approach. In the emerging field of theranostics, imaging tools together with therapeutic agents enable the selection of best treatments and allow tailored therapeutic interventions. For prenatal monitoring, the use of innovative imaging technologies can ensure an early detection of malfunctions or disease. The application of biomedical imaging for diagnosis and management of lifestyle-induced diseases will help to avoid disease development through lifestyle changes. Artificial intelligence and machine learning in imaging will facilitate the improvement of image interpretation and lead to better disease prediction and therapy planning. As biomedical imaging technologies and analysis of existing imaging data provide solutions to current challenges and needs in healthcare, appropriate funding for dedicated research is needed to implement the innovative approaches for the wellbeing of citizens and patients

    Pyramidalization of the Glycosidic Nitrogen Provides the Way for Efficient Cleavage of the N‑Glycosidic Bond of 8‑OxoG with the hOGG1 DNA Repair Protein

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    A mechanistic pathway for cleavage of the N-glycosidic bond of 8-oxo-2′-deoxyguanosine (oxoG) catalyzed with the human 8-oxoguanine glycosylase 1 DNA repair protein (hOGG1) is proposed in this theoretical study. The reaction scheme suggests direct proton addition to the glycosidic nitrogen N9 of oxoG from the Nε-ammonium of Lys249 residue of hOGG1 that is enabled owing to the N9 pyramidal geometry. The N9-pyramidalization of oxoG is induced within hOGG1 active site. The coordination of N9 nitrogen to the Nε-ammonium of Lys249 unveiled by available crystal structures enables concerted, synchronous substitution of the N9−C1′ bond by the N9−H bond. The reaction is compared with other pathways already proposed by means of calculated activation energies. The ΔG# energy for the newly proposed reaction mechanism calculated with the B3LYP/6-31G(d,p) method 17.0 kcal mol−1 is significantly lower than ΔG# energies for other reactions employing attack of the Nε-amino group to the anomeric carbon C1′ of oxoG and attack of the Nε-ammonium to the N3 nitrogen of oxoG base. Moreover, activation energy for the oxoG cleavage proceeding via N9-pyramidalization is lower than energy calculated for normal G because the electronic state of the five-membered aromatic ring of oxoG is better suited for the reaction. The modification of aromatic character introduced by oxidation to the nucleobase thus seems to be the factor that is checked by hOGG1 to achieve base-specific cleavage

    Satellite gravity gradient grids for geophysics

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    The Gravity field and steady-state Ocean Circulation Explorer (GOCE) satellite aimed at determining the Earth’s mean gravity field. GOCE delivered gravity gradients containing directional information, which are complicated to use because of their error characteristics and because they are given in a rotating instrument frame indirectly related to the Earth. We compute gravity gradients in grids at 225 km and 255 km altitude above the reference ellipsoid corresponding to the GOCE nominal and lower orbit phases respectively, and find that the grids may contain additional high-frequency content compared with GOCE-based global models. We discuss the gradient sensitivity for crustal depth slices using a 3D lithospheric model of the North-East Atlantic region, which shows that the depth sensitivity differs from gradient to gradient. In addition, the relative signal power for the individual gradient component changes comparing the 225 km and 255 km grids, implying that using all components at different heights reduces parameter uncertainties in geophysical modelling. Furthermore, since gravity gradients contain complementary information to gravity, we foresee the use of the grids in a wide range of applications from lithospheric modelling to studies on dynamic topography, and glacial isostatic adjustment, to bedrock geometry determination under ice sheets

    Physical activity in an air-polluted environment: behavioral, psychological and neuroimaging protocol for a prospective cohort study (Healthy Aging in Industrial Environment study – Program 4)

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    BackgroundAir pollution has been linked to increased mortality and morbidity. The Program 4 of the Healthy Aging in Industrial Environment study investigates whether the health and wellbeing benefits of physical activity (PA) can be fully realized in individuals living in highly polluted environments. Herein, we introduce the behavioral, psychological and neuroimaging protocol of the study.MethodsThis is a prospective cohort study of N=1500 individuals aged 18-65years comparing: (1) individuals living in the highly polluted, industrial region surrounding the city of Ostrava (n=750), and (2) controls from the comparison region with relative low pollution levels in Southern Bohemia (n=750). Quota sampling is used to obtain samples balanced on age, gender, PA status (60% active runners vs. 40% insufficiently active). Participants are screened and complete baseline assessments through online questionnaires and in-person lab-based assessments of physiological, biomechanical, neuroimaging and cognitive function parameters. Prospective 12-month intensive monitoring of air pollution and behavioral parameters (PA, inactivity, and sleep) follows, with a focus on PA-related injuries and psychological factors through fitness trackers, smartphones, and mobile apps. Subsequently, there will be a 5-year follow-up of the study cohort.DiscussionThe design of the study will allow for (1) the assessment of both short-term variation and long-term change in behavioral parameters, (2) evaluation of the incidence of musculoskeletal injuries and psychological factors impacting behavior and injury recovery, and (3) the impact that air pollution status (and change) has on behavior, psychological resilience, and injury recovery. Furthermore, the integration of MRI techniques and cognitive assessment in combination with data on behavioral, biological and environmental variables will provide an opportunity to examine brain structure and cognitive function in relation to health behavior and air pollution, as well as other factors affecting resilience against and vulnerability to adverse changes in brain structure and cognitive aging. This study will help inform individuals about personal risk factors and decision-makers about the impact of environmental factors on negative health outcomes and potential underlying biological, behavioral and psychological mechanisms. Challenges and opportunities stemming from the timing of the study that coincided with the COVID-19 pandemic are also discussed.Web of Science211art. no. 12
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