An error estimator for real-time simulators based on model order reduction

Model order reduction (MOR) is one of the most appealing choices for real-time simulation of non-linear solids. In this work a method is presented in which real time performance is achieved by means of the o-line solution of a (high dimensional) parametric problem that provides a sort of response surface or computational vademecum. This solution is then evaluated in real-time at feedback rates compatible with haptic devices, for instance (i.e., more than 1kHz). This high dimensional problem can be solved without the limitations imposed by the curse of dimensionality by employing Proper Generalized Decomposition (PGD) methods. Essentially, PGD assumes a separated representation for the essential eld of the problem. Here, an error estimator is proposed for this type of solutions that takes into account the non-linear character of the studied problems. This error estimator allows to compute the necessary number of modes employed to obtain an approximation to the solution within a prescribed error tolerance in a given quantity of interest

A reduced order approach for probabilistic inversions of 3-D magnetotelluric data I: general formulation

Simulation-based probabilistic inversions of 3-D magnetotelluric (MT) data are arguably the best option to deal with the nonlinearity and non-uniqueness of the MT problem. However, the computational cost associated with the modelling of 3-D MT data has so far precluded the community from adopting and/or pursuing full probabilistic inversions of large MT data sets. In this contribution, we present a novel and general inversion framework, driven by Markov Chain Monte Carlo (MCMC) algorithms, which combines (i) an efficient parallel-in-parallel structure to solve the 3-D forward problem, (ii) a reduced order technique to create fast and accurate surrogate models of the forward problem and (iii) adaptive strategies for both the MCMC algorithm and the surrogate model. In particular, and contrary to traditional implementations, the adaptation of the surrogate is integrated into the MCMC inversion. This circumvents the need of costly offline stages to build the surrogate and further increases the overall efficiency of the method. We demonstrate the feasibility and performance of our approach to invert for large-scale conductivity structures with two numerical examples using different parametrizations and dimensionalities. In both cases, we report staggering gains in computational efficiency compared to traditional MCMC implementations. Our method finally removes the main bottleneck of probabilistic inversions of 3-D MT data and opens up new opportunities for both stand-alone MT inversions and multi-observable joint inversions for the physical state of the Earth's interior.Fil: Manassero, María Constanza. Macquarie University; AustraliaFil: Afonso, Juan Carlos. Macquarie University; AustraliaFil: Zyserman, Fabio Ivan. Universidad Nacional de La Plata. Facultad de Ciencias Astronómicas y Geofísicas. Departamento de Geofísica Aplicada; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata; ArgentinaFil: Zlotnik, Sergio. Universidad Politécnica de Catalunya; EspañaFil: Fomin, I.. Macquarie University; Australi

A reduced order approach for probabilistic inversions of 3D magnetotelluric data II: joint inversion of MT and surface-wave data

Joint probabilistic inversions of magnetotelluric (MT) and seismic data have great potential for imaging the thermochemical structure of the lithosphere as well as mapping fluid/melt pathways and regions of mantle metasomatism. In this contribution, we present a novel probabilistic (Bayesian) joint inversion scheme for 3D MT and surface-wave dispersion data particularly designed for large-scale lithospheric studies. The approach makes use of a recently developed strategy for fast solutions of the 3D MT forward problem (Manassero et al., 2020, https://doi.org/10.1093/gji/ggaa415) and combines it with adaptive Markov chain Monte Carlo (MCMC) algorithms and parallel-in-parallel strategies to achieve extremely efficient simulations. To demonstrate the feasibility, benefits and performance of our joint inversion method for imaging the temperature and conductivity structures of the lithosphere, we apply it to two numerical examples of increasing complexity. The inversion approach presented here is timely and will be useful in the joint analysis of MT and surface wave data that are being collected in many parts of the world. This approach also opens up new avenues for the study of trans-lithospheric and trans-crustal magmatic systems, the detection of metasomatized mantle, and the incorporation of MT into multi-observable inversions for the physical state of the Earth's interior.We thank Farshad Salajegheh for providing part of his Matlab codes for plotting results 850 Special thanks to Kate Selway and Anandaroop Ray for their suggestions at different 851 stages of this work. The 3D rendering views were created using ParaView (Ahrens et al., 852 2005). 853 MCM thanks support from an International Macquarie Research Excellence Schol854 arship (iMQRES). MCM and JCA acknowledge support from ARC Grant DP160103502, 855 ARC Linkage Grant LP170100233, the ARC Centre of Excellence Core to Crust Fluids 856 Systems (http://www.ccfs.mq.edu.au) and the Centre for Earth Evolution and Dynam857 ics, Geoscience Australia and the European Space Agency via the “3D Earth - A Dy858 namic Living Planet”. FZ acknowledges support from CONICET through grant PIP 112- 859 201501-00192. SZ has been funded by the Spanish Ministry through grant DPI2017-85139- 860 C2-2-R, by Catalan government through grant 2017-SGR-1278 and by the EU’s Hori861 zon 2020 research and innovation programme under the Marie Sklodowska-Curie grant 862 agreement No 777778.Peer ReviewedPostprint (author's final draft

CXCR2 deficient mice display macrophage-dependent exaggerated acute inflammatory responses

CXCR2 is an essential regulator of neutrophil recruitment to inflamed and damaged sites and plays prominent roles in inflammatory pathologies and cancer. It has therefore been highlighted as an important therapeutic target. However the success of the therapeutic targeting of CXCR2 is threatened by our relative lack of knowledge of its precise in vivo mode of action. Here we demonstrate that CXCR2-deficient mice display a counterintuitive transient exaggerated inflammatory response to cutaneous and peritoneal inflammatory stimuli. In both situations, this is associated with reduced expression of cytokines associated with the resolution of the inflammatory response and an increase in macrophage accumulation at inflamed sites. Analysis using neutrophil depletion strategies indicates that this is a consequence of impaired recruitment of a non-neutrophilic CXCR2 positive leukocyte population. We suggest that these cells may be myeloid derived suppressor cells. Our data therefore reveal novel and previously unanticipated roles for CXCR2 in the orchestration of the inflammatory response

Blood-Brain Barrier Breakdown in a Single Post-stroke Rodent Brain

Stroke is a major cause of global morbidity and mortality. Middle cerebral artery occlusion (MCAO) has historically been the most common animal model of simulating ischemic stroke. The extent of neurological injury after MCAO is typically measured by cerebral edema, infarct zone, and blood-brain barrier (BBB) permeability. A significant limitation of these methods is that separate sets of brains must be used for each measurement. Here we examine an alternative method of measuring cerebral edema, infarct zone and BBB permeability following MCAO in the same set of brain samples. Ninety-six rats were randomly divided into three experimental groups. Group 1 (n = 27) was used for the evaluation of infarct zone and brain edema in rats post-MCAO (n = 17) vs. sham-operated controls (n = 10). Group 2 (n = 27) was used for the evaluation of BBB breakdown in rats post-MCAO (n = 15) vs. sham-operated controls (n = 10). In Group 3 (n = 42), all three parameters were measured in the same set of brain slices in rats post-MCAO (n = 26) vs. sham-operated controls (n = 16). The effect of Evans blue on the accuracy of measuring infarct zone by 2,3,5-triphenyltetrazolium chloride (TTC) staining was determined by measuring infarct zone with and without an applied blue filter. The effects of various concentrations of TTC (0, 0.05, 0.35, 0.5, 1, and 2%) on the accuracy of measuring BBB permeability was also assessed. There was an increase in infarct volume (p < 0.01), brain edema (p < 0.01) and BBB breakdown (p < 0.01) in rats following MCAO compared to sham-operated controls, whether measured separately or together in the same set of brain samples. Evans blue had an effect on measuring infarct volume that was minimized by the application of a blue filter on scanned brain slices. There was no difference in the Evans blue extravasation index for the brain tissue samples without TTC compared to brain tissue samples incubated in TTC. Our results demonstrate that measuring cerebral edema, infarct zone and BBB permeability following MCAO can accurately be measured in the same set of brain samples

СОВРЕМЕННОЕ СОСТОЯНИЕ СТАДА И МОРФОЛОГИЧЕСКАЯ ХАРАКТЕРИСТИКА ЛЕЩА ABRAMIS BRAMA (L.) ИЗ р. ЧУЛЫМА (БАССЕЙН р. ОБИ)

The article reveals data on bream inhabitance and its significance in fishing in the midstream basin of the river Chulym. The paper analyzes the catch and reveals the fact that bream catch is equal to the catch of wild fish in the river Chulym. The authors demonstrate morphological characteristics of the bream. They reveal the tendencies in changes of plastic features according to the sex and age and length features of the bream. The research studied bream males and females and their 25 plastic features; it found out bream males and females have variations on 8 features. Variations on 2 features were of great significance. The analysis of age and length variations revealed 3 groups of features which demonstrated different relation to linear growth of fish (the authors applied method of correlation analysis). The first group contains features which show weak relation between fish length (length of the head) and these features. The second group includes features demonstrating positive allometric growth; the third group contains features demonstrating negative allometric growth. The article reveals comparative analysis of plastic features between the midstream Chulym bream and the midstream Ob bream in order to estimate environmental variation. The samples were compared on 25 features and differed on 6 features. The authors found out the bream inhabited in the midstream Chulym is much similar to population of the Ob bream population.Получены данные по распространению леща и его значению в промысле в пределах бассейна среднего течения р. Чулыма. В ходе анализа данных промыслового улова выявлено, что вылов леща занимает равное положение с выловом основных промысловых рыб Чулыма. Представлены результаты исследований его морфологии. Выявлены тенденции в изменении пластических признаков в зависимости от пола и размерно-возрастных характеристик леща. Из 25 пластических признаков, исследованных у самцов и самок леща, были обнаружены достоверные различия по 8. По двум признакам различия имели самый высокий уровень значимости. Анализ размерно-возрастной изменчивости леща выявил три группы признаков, которые показывали различные фор- мы зависимости от линейного роста рыб (для этих целей был применен метод корреляционного анализа). Первая группа объединила признаки, которые не показали сколько-нибудь выраженную зависимость или обнаружили слабую связь между длиной рыбы (длиной головы) и  значениями этих признаков. Во вторую группу вошли признаки, показывающие положительную аллометрию. В третью группу вошли признаки, которые показали отрицательную аллометрию. Для оценки экологической изменчивости был проведен сравнительный анализ пластических признаков между лещом среднего течения Чулыма и среднего течения Оби. Из 25 сравниваемых признаков различия отмечены по 6. В результате проведенного морфологического анализа выяснили, что лещ среднего течения р. Чулым весьма близок с популяцией леща из р. Оби

3D Profile-Based Approach to Proteome-Wide Discovery of Novel Human Chemokines

Chemokines are small secreted proteins with important roles in immune responses. They consist of a conserved three-dimensional (3D) structure, so-called IL8-like chemokine fold, which is supported by disulfide bridges characteristic of this protein family. Sequence- and profile-based computational methods have been proficient in discovering novel chemokines by making use of their sequence-conserved cysteine patterns. However, it has been recently shown that some chemokines escaped annotation by these methods due to low sequence similarity to known chemokines and to different arrangement of cysteines in sequence and in 3D. Innovative methods overcoming the limitations of current techniques may allow the discovery of new remote homologs in the still functionally uncharacterized fraction of the human genome. We report a novel computational approach for proteome-wide identification of remote homologs of the chemokine family that uses fold recognition techniques in combination with a scaffold-based automatic mapping of disulfide bonds to define a 3D profile of the chemokine protein family. By applying our methodology to all currently uncharacterized human protein sequences, we have discovered two novel proteins that, without having significant sequence similarity to known chemokines or characteristic cysteine patterns, show strong structural resemblance to known anti-HIV chemokines. Detailed computational analysis and experimental structural investigations based on mass spectrometry and circular dichroism support our structural predictions and highlight several other chemokine-like features. The results obtained support their functional annotation as putative novel chemokines and encourage further experimental characterization. The identification of remote homologs of human chemokines may provide new insights into the molecular mechanisms causing pathologies such as cancer or AIDS, and may contribute to the development of novel treatments. Besides, the genome-wide applicability of our methodology based on 3D protein family profiles may open up new possibilities for improving and accelerating protein function annotation processes

Analysis of the temporal expression of chemokines and chemokine receptors during experimental granulomatous inflammation: role and expression of MIP-1Α and MCP-1

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/72640/1/sj.bjp.0704371.pd