36 research outputs found
The immunoglobulin tail tyrosine motif upgrades memory-type BCRs by incorporating a Grb2-Btk signalling module
No full textThe vigorous response of IgG-switched memory B cells to recurring pathogens involves enhanced signalling from their B-cell antigen receptors (BCRs). However, the molecular signal amplification mechanisms of memory-type BCRs remained unclear. Here, we identify the immunoglobulin tail tyrosine (ITT) motif in the cytoplasmic segments of membrane-bound IgGs (mIgGs) as the principle signal amplification device of memory-type BCRs in higher vertebrates and decipher its signalling microanatomy. We show that different families of protein tyrosine kinases act upstream and downstream of the ITT. Spleen tyrosine kinase (Syk) activity is required for ITT phosphorylation followed by recruitment of the adaptor protein Grb2 into the mIgG-BCR signalosome. Grb2 in turn recruits Bruton's tyrosine kinase (Btk) to amplify BCR-induced Ca2+ mobilization. This molecular interplay of kinases and adaptors increases the antigen sensitivity of memory-type BCRs, which provides a cell-intrinsic trigger mechanism for the rapid reactivation of IgG-switched memory B cells on antigen recall
Recruitment of the cytoplasmic adaptor Grb2 to surface IgG and IgE provides antigen receptor–intrinsic costimulation to class-switched B cells
No full textThe improved antibody responses of class-switched memory B cells depend on enhanced signaling from their B cell antigen receptors (BCRs). However, BCRs on both naive and antigen-experienced B cells use the canonical immunoglobulin-associated alpha and beta-protein signaling subunits. Here we identified a BCR isotype-specific signal-amplification mechanism. Whereas immunoglobulin M (IgM)-containing BCRs initiated intracellular signals exclusively through immunoglobulin-associated alpha- and beta-proteins, IgG- and IgE-containing BCRs also used a conserved tyrosine residue in the cytoplasmic segments of immunoglobulin heavy chains. When phosphorylated, this tyrosine recruited the adaptor Grb2, resulting in sustained protein kinase activation and prolonged generation of second messengers, which together culminated in enhanced B cell proliferation. Hence, membrane-bound IgG and IgE exert antigen recognition as well as costimulatory functions, thereby rendering memory B cells less dependent on T cell help
Tracking A Person Using UWB Pulse Doppler Radar
No full textThere are today a large number of different tracking systems and the subject of tracking targets is not a new one. A lot of the tracking done is in connection with aviation and military uses, but as the "internet of things" has become more popular the possibility to expand to households has appeared. To be able to track people in buildings or your own house opens a lot of possibilities for different applications, for example in home security.
The usage of small radars, in the size of a few square centimeters, for tracking in households was an interesting topic for Novelda AS, which this thesis was written in collaboration with. The task was therefore to create a tracking system using Novelda's Xethru short-range radars, to track a walking person in a room.
A tracking system was developed to be used in said environment. The total system consisted of four main parts. The first part was the kalman filter. The kalman filter smoothed out noisy data and provided estimates of the range and speed of the target. Then the gating was implemented, allowing only measurements from the radar that was within a certain range from the predicted position. Then, in the case when there was received multiple measurements at the same time, the global nearest neighbour method chose the measurement closest to the predicted position. In the end, a triangulation function was made to give out a final position using the two radars.
The thesis first gave a thorough description of the problem. Important parts of the tracking system was then explained and implemented. The system was then tested in simulations and later with real radar measurements. All the simulation and real radar measurements results were then presented in various plots and then discussed.
Topics for further work were discussed and in the end a conclusion was drawn. It was concluded that the tracking system provided satisfactory results relative to the SNRs given. The simulation gave a good track estimation up to 5.66 m distance from origo, while the real radar measurements gave the same at 4 m. The author then concluded that the tracking system algorithm performed well, but not well enough for it to be used in any household tracking system with its current SNR values. The performance could be improved by following some of the suggestions mentioned in further work
Tracking A Person Using UWB Pulse Doppler Radar
No full textThere are today a large number of different tracking systems and the subject of tracking targets is not a new one. A lot of the tracking done is in connection with aviation and military uses, but as the "internet of things" has become more popular the possibility to expand to households has appeared. To be able to track people in buildings or your own house opens a lot of possibilities for different applications, for example in home security.
The usage of small radars, in the size of a few square centimeters, for tracking in households was an interesting topic for Novelda AS, which this thesis was written in collaboration with. The task was therefore to create a tracking system using Novelda's Xethru short-range radars, to track a walking person in a room.
A tracking system was developed to be used in said environment. The total system consisted of four main parts. The first part was the kalman filter. The kalman filter smoothed out noisy data and provided estimates of the range and speed of the target. Then the gating was implemented, allowing only measurements from the radar that was within a certain range from the predicted position. Then, in the case when there was received multiple measurements at the same time, the global nearest neighbour method chose the measurement closest to the predicted position. In the end, a triangulation function was made to give out a final position using the two radars.
The thesis first gave a thorough description of the problem. Important parts of the tracking system was then explained and implemented. The system was then tested in simulations and later with real radar measurements. All the simulation and real radar measurements results were then presented in various plots and then discussed.
Topics for further work were discussed and in the end a conclusion was drawn. It was concluded that the tracking system provided satisfactory results relative to the SNRs given. The simulation gave a good track estimation up to 5.66 m distance from origo, while the real radar measurements gave the same at 4 m. The author then concluded that the tracking system algorithm performed well, but not well enough for it to be used in any household tracking system with its current SNR values. The performance could be improved by following some of the suggestions mentioned in further work
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No full textDecomposing the time-frequency representation of EEG using nonnegative matrix and multi-way factorizatio
Wind Gust Factors in a Coastal Wind Climate
No full textAbstractGust wind speeds in high wind speed conditions are important for load estimation on large structures in exposed locations, like a multi-megawatt wind turbine. Modern wind turbines operate at wind speeds up to 25 m/s so it is important to know the expected amplitude, acceleration and relevant scale of typical wind gusts under operating conditions.The wind measurement station at Frøya is located near the village of Titran on the western tip of the island. The site (Fig. 1) is well suited for measuring coastal and marine wind conditions relevant for offshore and coastal wind farms. The database contains several hundred hours of wind data from high wind speed conditions (>15 m/s). A 100 meter high meteorological mast with 2D ultrasonic anemometers at 6 levels have been used to collect wind data over a time period of 5 years from 2009 to 2014.Gust factors (G) measured at Frøya have been studied and correlated with height, wind speed, turbulence intensity (TI) and atmospheric stability, and compared to existing models.The gust factor mainly depends on turbulence intensity and gust averaging time. This indicates that the “peak factor” (kP) is a better measure for gustiness when turbulence values are available. kP decreases with increasing turbulence intensity and averaging time, but is less dependent on atmospheric stability. Its pdf follows a Gumbel distribution. An asymmetry of the measured gusts could be observed, showing a higher fall time compared to rise time
Stedet i litteraturen
No full textThis rapport studies the experience of place in the novel Jævnet med jorden written by the Danish author Mette Moestrup in 2009. Western thinking has traditionally viewed place as a secondary phenomenon compared to time and space. But this project is based upon the conviction that place is where human experience begins. Moestrups novel consists of 68 fragments, together forming a written collage. The novel follows a female narrator in her attempt to come to terms with the relationship to her childhood home (an old mill). The rapport employs an essayistic method inspired by literature scholar Dan Ringgard and consist of four essays, each dealing with the novel from different angles. The first essay focuses on the meanings of the narrator's white workroom and her attempt to rationally grasp her connection to the childhood place. The second essay examines the narrator's relationship to the mill and her boyfriend Morten. The third essay grapples with the relationship between place and memory. The last essay examines the so called re-enchantment of the place. In the end of the rapport place is discussed in more general terms and it is concluded that place is something that lies between the person who experiencing it and the physical place.This rapport studies the experience of place in the novel Jævnet med jorden written by the Danish author Mette Moestrup in 2009. Western thinking has traditionally viewed place as a secondary phenomenon compared to time and space. But this project is based upon the conviction that place is where human experience begins. Moestrups novel consists of 68 fragments, together forming a written collage. The novel follows a female narrator in her attempt to come to terms with the relationship to her childhood home (an old mill). The rapport employs an essayistic method inspired by literature scholar Dan Ringgard and consist of four essays, each dealing with the novel from different angles. The first essay focuses on the meanings of the narrator's white workroom and her attempt to rationally grasp her connection to the childhood place. The second essay examines the narrator's relationship to the mill and her boyfriend Morten. The third essay grapples with the relationship between place and memory. The last essay examines the so called re-enchantment of the place. In the end of the rapport place is discussed in more general terms and it is concluded that place is something that lies between the person who experiencing it and the physical place
From the 'Rescue of the Nation State' to the Emergence of European Spaces. EUIJ-Kansai Workshop on "New Research Horizons of the History of European Integration", May 10, 2008, Toyonaka (Osaka)
No full textThe aim of this paper is to make some contribution to the discussion on the future direction of the historical research on the European integration processes. What I intend to do here is, broadly, to link the contemporary European studies to the Historical studies, and concretely, to emphasise the transnational dimension of European integration. This exercise should be read as presenting my "wish list" to the Integration Historians
Microbiological Etiology in Patients with IE Undergoing Surgery and for Patients with Medical Treatment Only:A Nationwide Study from 2010 to 2020
No full textfirst_pagesettingsOrder Article ReprintsOpen AccessArticleMicrobiological Etiology in Patients with IE Undergoing Surgery and for Patients with Medical Treatment Only: A Nationwide Study from 2010 to 2020by Peter Laursen Graversen 1,*ORCID,Lauge Østergaard 1,Marianne Voldstedlund 2ORCID,Malthe Faurschou Wandall-Holm 3ORCID,Morten Holdgaard Smerup 4,Lars Køber 1,5 andEmil Loldrup Fosbøl 1,51Department of Cardiology, Copenhagen University Hospital—Rigshospitalet, 2100 Copenhagen, Denmark2Department of Data Integration and Analysis, Statens Serum Institut, 2300 Copenhagen, Denmark3Danish Multiple Sclerosis Registry, Department of Neurology, University of Copenhagen—Rigshospitalet, 2600 Glostrup, Denmark4Department of Cardiothoracic Surgery, Copenhagen University Hospital—Rigshospitalet, 2100 Copenhagen, Denmark5Department of Clinical Medicine, University of Copenhagen, 2200 Copenhagen, Denmark*Author to whom correspondence should be addressed.Microorganisms 2023, 11(10), 2403; https://doi.org/10.3390/microorganisms11102403Original submission received: 10 July 2023 / Revised: 21 September 2023 / Accepted: 23 September 2023 / Published: 26 September 2023(This article belongs to the Special Issue The Infective Endocarditis)Downloadkeyboard_arrow_down Browse Figures Review Reports Versions NotesAbstractMicrobiological etiology has been associated with surgery for infective endocarditis (IE) during admission, especially Staphylococcus aureus. We aimed to compare patient characteristics, microbiological characteristics, and outcomes by treatment choice (surgery or not). We identified patients with first-time IE between 2010 and 2020 and examined the microbiological etiology of IE according to treatment choice. To identify factors associated with surgery during initial admission, we used the Aalen–Johansen estimator and an adjusted cause-specific Cox model. One-year mortality stratified by microbiological etiology and treatment choice was assessed using unadjusted Kaplan–Meier estimates and an adjusted Cox proportional hazard model. A total of 6255 patients were included, of which 1276 (20.4%) underwent surgery during admission. Patients who underwent surgery were younger (65 vs. 74 years) and less frequently had cerebrovascular disease, cardiovascular disease, diabetes, and chronic kidney disease. Patients with Staphylococcus aureus IE were less likely to undergo surgery during admission (13.6%) compared to all other microbiological etiologies. One-year mortality according to microbiological etiology in patients who underwent surgery was 7.0%, 5.3%, 5.5%, 9.6%, 13.2, and 11.2% compared with 24.2%, 19.1%, 27,6%, 25.2%, 21%, and 16.9% in patients who received medical therapy for Staphylococcus aureus, Streptococcus spp., Enterococcus spp., coagulase-negative Staphylococci, “other microbiological etiologies”, and blood culture-negative infective endocarditis, respectively. Patients with IE who underwent surgery differed in terms of microbiology, more often having Streptococci than those who received medical therapy. Contrary to expectations, Staphylococcus aureus was more common among patients who received medical therapy only.Keywords: microorganism; infective endocarditis; surgery; microbiological etiology; microbiological characteristicsMicrobiological etiology has been associated with surgery for infective endocarditis (IE) during admission, especially Staphylococcus aureus. We aimed to compare patient characteristics, microbiological characteristics, and outcomes by treatment choice (surgery or not). We identified patients with first-time IE between 2010 and 2020 and examined the microbiological etiology of IE according to treatment choice. To identify factors associated with surgery during initial admission, we used the Aalen–Johansen estimator and an adjusted cause-specific Cox model. One-year mortality stratified by microbiological etiology and treatment choice was assessed using unadjusted Kaplan–Meier estimates and an adjusted Cox proportional hazard model. A total of 6255 patients were included, of which 1276 (20.4%) underwent surgery during admission. Patients who underwent surgery were younger (65 vs. 74 years) and less frequently had cerebrovascular disease, cardiovascular disease, diabetes, and chronic kidney disease. Patients with Staphylococcus aureus IE were less likely to undergo surgery during admission (13.6%) compared to all other microbiological etiologies. One-year mortality according to microbiological etiology in patients who underwent surgery was 7.0%, 5.3%, 5.5%, 9.6%, 13.2, and 11.2% compared with 24.2%, 19.1%, 27,6%, 25.2%, 21%, and 16.9% in patients who received medical therapy for Staphylococcus aureus, Streptococcus spp., Enterococcus spp., coagulase-negative Staphylococci, “other microbiological etiologies”, and blood culture-negative infective endocarditis, respectively. Patients with IE who underwent surgery differed in terms of microbiology, more often having Streptococci than those who received medical therapy. Contrary to expectations, Staphylococcus aureus was more common among patients who received medical therapy only.</p
A Logical Relation for Monadic Encapsulation of State: Proving contextual equivalences in the presence of runST
No full textWe present a logical relations model of a higher-order functional programming language with impredicative polymorphism, recursive types, and a Haskell-style ST monad type with runST. We use our logical relations model to show that runST provides proper encapsulation of state, by showing that e effectful computations encapsulated by runST are heap independent. Furthermore, we show that contextual refinements and equivalences that are expected to hold for pure computations do indeed hold in the presence of runST. This is the first time such relational results have been proven for a language with monadic encapsulation of state. We have formalized all the technical development and results in Coq.sponsorship: The last author would like to thank Georg Neis for early discussions about the topic of this paper. We would like to thank the anonymous referees for their invaluable constructive comments. This research was supported in part by the ModuRes Sapere Aude Advanced Grant from The Danish Council for Independent Research for the Natural Sciences (FNU), by the EUTypes funding ECOST-STSM-CA15123-150816-080859 and by the Flemish Research Fund grants G.0058.13 (until June 2017) and G.0962.17N (since July 2017). (Danish Council for Independent Research for the Natural Sciences (FNU), EUTypes|ECOST-STSM-CA15123-150816-080859, Flemish Research Fund|G.0058.13, Flemish Research Fund|G.0962.17N)status: Publishe
