| 1. |
- Allesøe, Rosa Lundbye, et al.
(författare)
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Discovery of drug–omics associations in type 2 diabetes with generative deep-learning models
- 2023
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Ingår i: Nature Biotechnology. - : Springer Nature. - 1087-0156 .- 1546-1696. ; 41:3, s. 399-408
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Tidskriftsartikel (refereegranskat)abstract
- The application of multiple omics technologies in biomedical cohorts has the potential to reveal patient-level disease characteristics and individualized response to treatment. However, the scale and heterogeneous nature of multi-modal data makes integration and inference a non-trivial task. We developed a deep-learning-based framework, multi-omics variational autoencoders (MOVE), to integrate such data and applied it to a cohort of 789 people with newly diagnosed type 2 diabetes with deep multi-omics phenotyping from the DIRECT consortium. Using in silico perturbations, we identified drug–omics associations across the multi-modal datasets for the 20 most prevalent drugs given to people with type 2 diabetes with substantially higher sensitivity than univariate statistical tests. From these, we among others, identified novel associations between metformin and the gut microbiota as well as opposite molecular responses for the two statins, simvastatin and atorvastatin. We used the associations to quantify drug–drug similarities, assess the degree of polypharmacy and conclude that drug effects are distributed across the multi-omics modalities.
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| 2. |
- Kasai, Y., et al.
(författare)
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Validation of stratospheric and mesospheric ozone observed by SMILES from International Space Station
- 2013
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Ingår i: Atmospheric Measurement Techniques. - : Copernicus GmbH. - 1867-1381 .- 1867-8548. ; 6:9, s. 2311-2338
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Tidskriftsartikel (refereegranskat)abstract
- We observed ozone (O3) in the vertical region between 250 and 0.0005 hPa (~ 12–96 km) using the Superconducting Submillimeter-Wave Limb-Emission Sounder (SMILES) on the Japanese Experiment Module (JEM) of the International Space Station (ISS) between 12 October 2009 and 21 April 2010. The new 4 K superconducting heterodyne receiver technology of SMILES allowed us to obtain a one order of magnitude better signal-to-noise ratio for the O3 line observation compared to past spaceborne microwave instruments. The non-sun-synchronous orbit of the ISS allowed us to observe O3 at various local times. We assessed the quality of the vertical profiles of O3 in the 100–0.001 hPa (~ 16–90 km) region for the SMILES NICT Level 2 product version 2.1.5. The evaluation is based on four components: error analysis; internal comparisons of observations targeting three different instrumental setups for the same O3 625.371 GHz transition; internal comparisons of two different retrieval algorithms; and external comparisons for various local times with ozonesonde, satellite and balloon observations (ENVISAT/MIPAS, SCISAT/ACE-FTS, Odin/OSIRIS, Odin/SMR, Aura/MLS, TELIS). SMILES O3 data have an estimated absolute accuracy of better than 0.3 ppmv (3%) with a vertical resolution of 3–4 km over the 60 to 8 hPa range. The random error for a single measurement is better than the estimated systematic error, being less than 1, 2, and 7%, in the 40–1, 80–0.1, and 100–0.004 hPa pressure regions, respectively. SMILES O3 abundance was 10–20% lower than all other satellite measurements at 8–0.1 hPa due to an error arising from uncertainties of the tangent point information and the gain calibration for the intensity of the spectrum. SMILES O3 from observation frequency Band-B had better accuracy than that from Band-A. A two month period is required to accumulate measurements covering 24 h in local time of O3 profile. However such a dataset can also contain variation due to dynamical, seasonal, and latitudinal effects
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| 3. |
- Mayer, Peter, et al.
(författare)
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Productivity vs security: mitigating conflicting goals in organizations
- 2017
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Ingår i: Information and Computer Security. - Bingley : Emerald Group Publishing Limited. - 2056-4961. ; 25:2, s. 137-151
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Tidskriftsartikel (refereegranskat)abstract
- PurposeThis paper aims to contribute to the understanding of goal setting in organizations, especially regarding the mitigation of conflicting productivity and security goals.Design/methodology/approachThis paper describes the results of a survey with 200 German employees regarding the effects of goal setting on employees’ security compliance. Based on the survey results, a concept for setting information security goals in organizations building on actionable behavioral recommendations from information security awareness materials is developed. This concept was evaluated in three small- to medium-sized organizations (SMEs) with overall 90 employees.FindingsThe survey results revealed that the presence of rewards for productivity goal achievement is strongly associated with a decrease in security compliance. The evaluation of the goal setting concept indicates that setting their own information security goals is welcomed by employees.Research limitations/implicationsBoth studies rely on self-reported data and are, therefore, likely to contain some kind of bias.Practical implicationsGoal setting in organizations has to accommodate for situations, where productivity goals constrain security policy compliance. Introducing the proposed goal setting concept based on relevant actionable behavioral recommendations can help mitigate issues in such situations.Originality/valueThis work furthers the understanding of the factors affecting employee security compliance. Furthermore, the proposed concept can help maximizing the positive effects of goal setting in organizations by mitigating the negative effects through the introduction of meaningful and actionable information security goals.
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| 4. |
- Sarris, Theodore E., et al.
(författare)
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Daedalus MASE (mission assessment through simulation exercise): A toolset for analysis of in situ missions and for processing global circulation model outputs in the lower thermosphere-ionosphere
- 2023
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Ingår i: Frontiers in Astronomy and Space Sciences. - : Frontiers Media SA. - 2296-987X. ; 9
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Tidskriftsartikel (refereegranskat)abstract
- Daedalus MASE (Mission Assessment through Simulation Exercise) is an open-source package of scientific analysis tools aimed at research in the Lower Thermosphere-Ionosphere (LTI). It was created with the purpose to assess the performance and demonstrate closure of the mission objectives of Daedalus, a mission concept targeting to perform in-situ measurements in the LTI. However, through its successful usage as a mission-simulator toolset, Daedalus MASE has evolved to encompass numerous capabilities related to LTI science and modeling. Inputs are geophysical observables in the LTI, which can be obtained either through in-situ measurements from spacecraft and rockets, or through Global Circulation Models (GCM). These include ion, neutral and electron densities, ion and neutral composition, ion, electron and neutral temperatures, ion drifts, neutral winds, electric field, and magnetic field. In the examples presented, these geophysical observables are obtained through NCAR’s Thermosphere-Ionosphere-Electrodynamics General Circulation Model. Capabilities of Daedalus MASE include: 1) Calculations of products that are derived from the above geophysical observables, such as Joule heating, energy transfer rates between species, electrical currents, electrical conductivity, ion-neutral collision frequencies between all combinations of species, as well as height-integrations of derived products. 2) Calculation and cross-comparison of collision frequencies and estimates of the effect of using different models of collision frequencies into derived products. 3) Calculation of the uncertainties of derived products based on the uncertainties of the geophysical observables, due to instrument errors or to uncertainties in measurement techniques. 4) Routines for the along-orbit interpolation within gridded datasets of GCMs. 5) Routines for the calculation of the global coverage of an in situ mission in regions of interest and for various conditions of solar and geomagnetic activity. 6) Calculations of the statistical significance of obtaining the primary and derived products throughout an in situ mission’s lifetime. 7) Routines for the visualization of 3D datasets of GCMs and of measurements along orbit. Daedalus MASE code is accompanied by a set of Jupyter Notebooks, incorporating all required theory, references, codes and plotting in a user-friendly environment. Daedalus MASE is developed and maintained at the Department for Electrical and Computer Engineering of the Democritus University of Thrace, with key contributions from several partner institutions.
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| 5. |
- Vogt, Elinor Chelsom, et al.
(författare)
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Premature menopause and autoimmune primary ovarian insufficiency in two international multi-center cohorts
- 2022
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Ingår i: Endocrine Connections. - : Bioscientifica. - 2049-3614. ; 11:5
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Tidskriftsartikel (refereegranskat)abstract
- Objective: To investigate markers of premature menopause (<40 years) and specifically the prevalence of autoimmune primary ovarian insufficiency (POI) in European women.Design: Postmenopausal women were categorized according to age at menopause and self-reported reason for menopause in a cross-sectional analysis of 6870 women.Methods: Variables associated with the timing of menopause and hormone measurements of 17β-estradiol and follicle-stimulating hormone were explored using multivariable logistic regression analysis. Specific immunoprecipitating assays of steroidogenic autoantibodies against 21-hydroxylase (21-OH), side-chain cleavage enzyme (anti-SCC) and 17alpha-hydroxylase (17 OH), as well as NACHT leucine-rich-repeat protein 5 were used to identify women with likely autoimmune POI.Results: Premature menopause was identified in 2.8% of women, and these women had higher frequencies of nulliparity (37.4% vs 19.7%), obesity (28.7% vs 21.4%), osteoporosis (17.1% vs 11.6%), hormone replacement therapy (59.1% vs 36.9%) and never smokers (60.1% vs 50.9%) (P < 0.05), compared to women with menopause ≥40 years. Iatrogenic causes were found in 91 (47%) and non-ovarian causes in 27 (14%) women, while 77 (39%) women were classified as POI of unknown cause, resulting in a 1.1% prevalence of idiopathic POI. After adjustments nulliparity was the only variable significantly associated with POI (odds ratio 2.46; 95% CI 1.63-3.42). Based on the presence of autoantibodies against 21 OH and SCC, 4.5% of POI cases were of likely autoimmune origin.Conclusion: Idiopathic POI affects 1.1% of all women and almost half of the women with premature menopause. Autoimmunity explains 4.5% of these cases judged by positive steroidogenic autoantibodies.
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| 6. |
- Vogt, Joachim, et al.
(författare)
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Daedalus Ionospheric Profile Continuation (DIPCont) : Monte Carlo studies assessing the quality of in situ measurement extrapolation
- 2023
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Ingår i: Geoscientific Instrumentation, Methods and Data Systems. - : Copernicus Publications. - 2193-0856 .- 2193-0864. ; 12:2, s. 239-257
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Tidskriftsartikel (refereegranskat)abstract
- In situ satellite exploration of the lower thermosphere-ionosphere system (LTI) as anticipated in the recent Daedalus mission proposal to ESA will be essential to advance the understanding of the interface between the Earth's atmosphere and its space environment. To address physical processes also below perigee, in situ measurements are to be extrapolated using models of the LTI. Motivated by the need for assessing how cost-critical mission elements such as perigee and apogee distances as well as the number of spacecraft affect the accuracy of scientific inference in the LTI, the Daedalus Ionospheric Profile Continuation (DIPCont) project is concerned with the attainable quality of in situ measurement extrapolation for different mission parameters and configurations. This report introduces the methodological framework of the DIPCont approach. Once an LTI model is chosen, ensembles of model parameters are created by means of Monte Carlo simulations using synthetic measurements based on model predictions and relative uncertainties as specified in the Daedalus Report for Assessment. The parameter ensembles give rise to ensembles of model altitude profiles for LTI variables of interest. Extrapolation quality is quantified by statistics derived from the altitude profile ensembles. The vertical extent of meaningful profile continuation is captured by the concept of extrapolation horizons defined as the boundaries of regions where the deviations remain below a prescribed error threshold. To demonstrate the methodology, the initial version of the DIPCont package presented in this paper contains a simplified LTI model with a small number of parameters. As a major source of variability, the pronounced change in temperature across the LTI is captured by self-consistent non-isothermal neutral-density and electron density profiles, constructed from scale height profiles that increase linearly with altitude. The resulting extrapolation horizons are presented for dual-satellite measurements at different inter-spacecraft distances but also for the single-satellite case to compare the two basic mission scenarios under consideration. DIPCont models and procedures are implemented in a collection of Python modules and Jupyter notebooks supplementing this report.
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