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Schriftenreihe
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- Bavarian Center for Applied Energy Research e.V. (ZAE Bayern) (1)
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Large-Scale Assessment of a Fully Automatic Co-Adaptive Motor Imagery-Based Brain Computer Interface
(2016)
In the last years Brain Computer Interface (BCI) technology has benefited from the development of sophisticated machine leaning methods that let the user operate the BCI after a few trials of calibration. One remarkable example is the recent development of co-adaptive techniques that proved to extend the use of BCIs also to people not able to achieve successful control with the standard BCI procedure. Especially for BCIs based on the modulation of the Sensorimotor Rhythm (SMR) these improvements are essential, since a not negligible percentage of users is unable to operate SMR-BCIs efficiently. In this study we evaluated for the first time a fully automatic co-adaptive BCI system on a large scale. A pool of 168 participants naive to BCIs operated the co-adaptive SMR-BCI in one single session. Different psychological interventions were performed prior the BCI session in order to investigate how motor coordination training and relaxation could influence BCI performance. A neurophysiological indicator based on the Power Spectral Density (PSD) was extracted by the recording of few minutes of resting state brain activity and tested as predictor of BCI performances. Results show that high accuracies in operating the BCI could be reached by the majority of the participants before the end of the session. BCI performances could be significantly predicted by the neurophysiological indicator, consolidating the validity of the model previously developed. Anyway, we still found about 22% of users with performance significantly lower than the threshold of efficient BCI control at the end of the session. Being the inter-subject variability still the major problem of BCI technology, we pointed out crucial issues for those who did not achieve sufficient control. Finally, we propose valid developments to move a step forward to the applicability of the promising co-adaptive methods.
Adolfi, Mateus C. ; Herpin, Amaury ; Regensburger, Martina ; Sacquegno, Jacopo ; Waxman, Joshua S. ; Schartl, Manfred
In vertebrates, one of the first recognizable sex differences in embryos is the onset of meiosis, known to be regulated by retinoic acid (RA) in mammals. We investigated in medaka a possible meiotic function of RA during the embryonic sex determination (SD) period and in mature gonads. We found RA mediated transcriptional activation in germ cells of both sexes much earlier than the SD stage, however, no such activity during the critical stages of SD. In adults, expression of the RA metabolizing enzymes indicates sexually dimorphic RA levels. In testis, RA acts directly in Sertoli, Leydig and pre-meiotic germ cells. In ovaries, RA transcriptional activity is highest in meiotic oocytes. Our results show that RA plays an important role in meiosis induction and gametogenesis in adult medaka but contrary to common expectations, not for initiating the first meiosis in female germ cells at the SD stage.
Adrián-Martínez, S. ; Ageron, M. ; Aharonian, F. ; Aiello, S. ; Albert, A. ; Ameli, F. ; Annasontzis, E. ; Andre, M. ; Androulakis, G. ; Anghinolfi, M. ; Anton, G. ; Ardid, M. ; Avgitas, T. ; Barbarino, G. ; Baret, B. ; Barrios-Martí, J. ; Belhorma, B. ; Belias, A. ; Berbee, A. ; van den Berg, A. ; Bertin, V. ; Beurthey, S. ; van Beeveren, V. ; Beverini, N. ; Biagi, S. ; Biagioni, A. ; Billault, M. ; Bondì, M. ; Bormuth, R. ; Bouhadef, B. ; Bourlis, G. ; Bourret, S. ; Boutonnet, C. ; Bouwhuis, M. ; Bozza, C. ; Bruijn, R. ; Brunner, J. ; Buis, E. ; Busto, J. ; Cacopardo, G. ; Caillat, L. ; Calmai, M. ; Calvo, D. ; Capone, A. ; Caramete, L. ; Cecchini, S. ; Celli, S. ; Champion, C. ; Cherkaoui El Moursli, R. ; Cherubini, S. ; Chiarusi, T. ; Circella, M. ; Classen, L. ; Cocimano, R. ; Coelho, J. A. B. ; Coleiro, A. ; Colonges, S. ; Coniglione, R. ; Cordelli, M. ; Cosquer, A. ; Coyle, P. ; Creusot, A. ; Cuttone, G. ; D'Amico, A. ; De Bonis, G. ; De Rosa, G. ; De Sio, C. ; Di Capua, F. ; Di Palma, I. ; Díaz García, A. F. ; Distefano, C. ; Donzaud, C. ; Dornic, D. ; Dorosti-Hasankiadeh, Q. ; Drakopoulou, E. ; Drouhin, D. ; Drury, L. ; Durocher, M. ; Eberl, T. ; Eichie, S. ; van Eijk, D. ; El Bojaddaini, I. ; El Khayati, N. ; Elsaesser, D. ; Enzenhöfer, A. ; Fassi, F. ; Favali, P. ; Fermani, P. ; Ferrara, G. ; Filippidis, C. ; Frascadore, G. ; Fusco, L. A. ; Gal, T. ; Galatà, S. ; Garufi, F. ; Gay, P. ; Gebyehu, M. ; Giordano, V. ; Gizani, N. ; Gracia, R. ; Graf, K. ; Grégoire, T. ; Grella, G. ; Habel, R. ; Hallmann, S. ; van Haren, H. ; Harissopulos, S. ; Heid, T. ; Heijboer, A. ; Heine, E. ; Henry, S. ; Hernández-Rey, J. J. ; Hevinga, M. ; Hofestädt, J. ; Hugon, C. M. F. ; Illuminati, G. ; James, C. W. ; Jansweijer, P. ; Jongen, M. ; de Jong, M. ; Kadler, M. ; Kalekin, O. ; Kappes, A. ; Katz, U. F. ; Keller, P. ; Kieft, G. ; Kießling, D. ; Koffeman, E. N. ; Kooijman, P. ; Kouchner, A. ; Kulikovskiy, V. ; Lahmann, R. ; Lamare, P. ; Leisos, A. ; Leonora, E. ; Lindsey Clark, M. ; Liolios, A. ; Llorenz Alvarez, C. D. ; Lo Presti, D. ; Löhner, H. ; Lonardo, A. ; Lotze, M. ; Loucatos, S. ; Maccioni, E. ; Mannheim, K. ; Margiotta, A. ; Marinelli, A. ; Mariş, O. ; Markou, C. ; Martínez-Mora, J. A. ; Martini, A. ; Mele, R. ; Melis, K. W. ; Michael, T. ; Migliozzi, P. ; Migneco, E. ; Mijakowski, P. ; Miraglia, A. ; Mollo, C. M. ; Mongelli, M. ; Morganti, M. ; Moussa, A. ; Musico, P. ; Musumeci, M. ; Navas, S. ; Nicoleau, C. A. ; Olcina, I. ; Olivetto, C. ; Orlando, A. ; Papaikonomou, A. ; Papaleo, R. ; Păvălaş, G. E. ; Peek, H. ; Pellegrino, C. ; Perrina, C. ; Pfutzner, M. ; Piattelli, P. ; Pikounis, K. ; Poma, G. E. ; Popa, V. ; Pradier, T. ; Pratolongo, F. ; Pühlhofer, G. ; Pulvirenti, S. ; Quinn, L. ; Racca, C. ; Raffaelli, F. ; Randazzo, N. ; Rapidis, P. ; Razis, P. ; Real, D. ; Resvanis, L. ; Reubelt, J. ; Riccobene, G. ; Rossi, C. ; Rovelli, A. ; Saldaña, M. ; Salvadori, I. ; Samtleben, D. F. E. ; Sánchez García, A. ; Sánchez Losa, A. ; Sanguineti, M. ; Santangelo, A. ; Santonocito, D. ; Sapienza, P. ; Schimmel, F. ; Schmelling, J. ; Sciacca, V. ; Sedita, M. ; Seitz, T. ; Sgura, I. ; Simeone, F. ; Siotis, I. ; Sipala, V. ; Spisso, B. ; Spurio, M. ; Stavropoulos, G. ; Steijger, J. ; Stellacci, S. M. ; Stransky, D. ; Taiuti, M. ; Tayalati, Y. ; Tézier, D. ; Theraube, S. ; Thompson, L. ; Timmer, P. ; Tönnis, C. ; Trasatti, L. ; Trovato, A. ; Tsirigotis, A. ; Tzamarias, S. ; Tzamariudaki, E. ; Vallage, B. ; Van Elewyk, V. ; Vermeulen, J. ; Vicini, P. ; Viola, S. ; Vivolo, D. ; Volkert, M. ; Voulgaris, G. ; Wiggers, L. ; Wilms, J. ; de Wolf, E. ; Zachariadou, K. ; Zornoza, J. D. ; Zúñiga, J.
The main objectives of the KM3NeT Collaboration are (i) the discovery and subsequent observation of high-energy neutrino sources in the Universe and (ii) the determination of the mass hierarchy of neutrinos. These objectives are strongly motivated by two recent important discoveries, namely: (1) the high-energy astrophysical neutrino signal reported by IceCube and (2) the sizable contribution of electron neutrinos to the third neutrino mass eigenstate as reported by Daya Bay, Reno and others. To meet these objectives, the KM3NeT Collaboration plans to build a new Research Infrastructure consisting of a network of deep-sea neutrino telescopes in the Mediterranean Sea. A phased and distributed implementation is pursued which maximises the access to regional funds, the availability of human resources and the synergistic opportunities for the Earth and sea sciences community. Three suitable deep-sea sites are selected, namely off-shore Toulon (France), Capo Passero (Sicily, Italy) and Pylos (Peloponnese, Greece). The infrastructure will consist of three so-called building blocks. A building block comprises 115 strings, each string comprises 18 optical modules and each optical module comprises 31 photo-multiplier tubes. Each building block thus constitutes a three-dimensional array of photo sensors that can be used to detect the Cherenkov light produced by relativistic particles emerging from neutrino interactions. Two building blocks will be sparsely configured to fully explore the IceCube signal with similar instrumented volume, different methodology, improved resolution and
Adrián-Martínez, S. ; Albert, A. ; André, M. ; Anghinolfi, M. ; Anton, G. ; Ardid, M. ; Aubert, J.-J. ; Avgitas, T. ; Baret, B. ; Barrios-Martí, J. ; Basa, S. ; Bertin, V. ; Biagi, S. ; Bormuth, R. ; Bouwhuis, M.C. ; Bruijn, R. ; Brunner, J. ; Busto, J. ; Capone, A. ; Caramete, L. ; Carr, J. ; Celli, S. ; Chiarusi, T. ; Circella, M. ; Coleiro, A. ; Coniglione, R. ; Constantini, H. ; Coyle, P. ; Creusot, A. ; Deschamps, A. ; De Bonis, G. ; Distefano, C. ; Donzaud, C. ; Dornic, D. ; Drouhin, D. ; Eberl, T. ; El Bojaddaini, I. ; Elsässer, D. ; Enzenhöfer, A. ; Fehn, K. ; Felis, I. ; Fusco, L.A. ; Galatà, S. ; Gay, P. ; Geißelsöder, S. ; Geyer, K. ; Giordano, V. ; Gleixner, A. ; Glotin, H. ; Gracia-Ruiz, R. ; Graf, K. ; Hallmann, S. ; van Haren, H. ; Heijboer, A.J. ; Hello, Y. ; Hernández-Rey, J.J. ; Hößl, J. ; Hofestädt, J. ; Hugon, C. ; Illuminati, G. ; James, C.W. ; de Jong, M. ; Kadler, M. ; Kalekin, O. ; Katz, U. ; Kießling, D. ; Kouchner, A. ; Kreter, M. ; Kreykenbohm, I. ; Kulikovskiy, V. ; Lachaud, C. ; Lahmann, R. ; Lefèvre, D. ; Leonora, E. ; Loucatos, S. ; Marcelin, M. ; Margiotta, A. ; Marinelli, A. ; Martínez-Mora, J.A. ; Mathieu, A. ; Michael, T. ; Migliozzi, P. ; Moussa, A. ; Mueller, C. ; Nezri, E. ; Pavalas, G.E. ; Pellegrino, C. ; Perrina, C. ; Piattelli, P. ; Popa, V. ; Pradier, T. ; Racca, C. ; Riccobene, G. ; Roensch, K. ; Saldaña, M. ; Samtleben, D.F.E. ; Sánchez-Losa, A. ; Sanguineti, M. ; Sapienza, P. ; Schnabel, J. ; Schüssler, F. ; Seitz, T. ; Sieger, C. ; Spurio, M. ; Stolarczyk, Th. ; Taiuti, M. ; Trovato, A. ; Tselengidou, M. ; Turpin, D. ; Tönnis, C. ; Vallage, B. ; Vallée, C. ; Van Elewyck, V. ; Visser, E. ; Vivolo, D. ; Wagner, S. ; Wilms, J. ; Zornoza, J.D. ; Zúñiga, J.
A highly significant excess of high-energy astrophysical neutrinos has been reported by the IceCube Collaboration. Some features of the energy and declination distributions of IceCube events hint at a North/South asymmetry of the neutrino flux. This could be due to the presence of the bulk of our Galaxy in the Southern hemisphere. The ANTARES neutrino telescope, located in the Mediterranean Sea, has been taking data since 2007. It offers the best sensitivity to muon neutrinos produced by galactic cosmic ray interactions in this region of the sky. In this letter a search for an extended neutrino flux from the Galactic Ridge region is presented. Different models of neutrino production by cosmic ray propagation are tested. No excess of events is observed and upper limits for different neutrino flux spectral indices Γ are set. For Γ=2.4 the 90% confidence level flux upper limit at 100 TeV for one neutrino flavour corresponds to Φ\(^{1f}_{0}\) (100 TeV) = 2.0 · 10\(^{−17}\) GeV\(^{−1}\) cm\(^{−2}\)s\(^{−1}\)sr\(^{−1}\). Under this assumption, at most two events of the IceCube cosmic candidates can originate from the Galactic Ridge. A simple power-law extrapolation of the Fermi-LAT flux to account for IceCube High Energy Starting Events is excluded at 90% confidence level.
Adrián-Martínez, S. ; Albert, A. ; André, M. ; Anton, G. ; Ardid, M. ; Aubert, J.-J. ; Avgitas, T. ; Baret, B. ; Barrios-Martí, J. ; Basa, S. ; Bertin, V. ; Biagi, S. ; Bormuth, R. ; Bou-Cabo, M. ; Bouwhuis, M.C. ; Bruijn, R. ; Brunner, J. ; Busto, J. ; Capone, A. ; Caramete, L. ; Carr, J. ; Celli, S. ; Chiarusi, T. ; Circella, M. ; Coleiro, A. ; Coniglione, R. ; Costantini, H. ; Coyle, P. ; Creusot, A. ; Deschamps, A. ; De Bonis, G. ; Distefano, C. ; Donzaud, C. ; Dornic, D. ; Drouhin, D. ; Eberl, T. ; El Bojaddaini, I. ; Elsässer, D. ; Enzenhöfer, A. ; Fehn, K. ; Felis, I. ; Fusco, L.A. ; Galatà, S. ; Gay, P. ; Geißelsöder, S. ; Geyer, K. ; Giordano, V. ; Gleixner, A. ; Glotin, H. ; Gracia-Ruiz, R. ; Graf, K. ; Hallmann, S. ; van Haren, H. ; Heijboer, A.J. ; Hello, Y. ; Hernández-Rey, J.-J. ; Hößl, J. ; Hofestädt, J. ; Hugon, C. ; Illuminati, G. ; James, C.W. ; de Jong, M. ; Kadler, M. ; Kalekin, O. ; Katz, U. ; Kießling, D. ; Kouchner, A. ; Kreter, M. ; Kreykenbohm, I. ; Kulikovskiy, V. ; Lachaud, C. ; Lahmann, R. ; Lefèvre, D. ; Leonora, E. ; Loucatos, S. ; Marcelin, M. ; Margiotta, A. ; Marinelli, A. ; Martínez-Mora, J.A. ; Mathieu, A. ; Michael, T. ; Migliozzi, P. ; Moussa, A. ; Mueller, C. ; Nezri, E. ; Păvălaș, G.E. ; Pellegrino, C. ; Perrina, C. ; Piattelli, P. ; Popa, V. ; Pradier, T. ; Racca, C. ; Riccobene, G. ; Roensch, K. ; Saldaña, M. ; Samtleben, D.F.E. ; Sanguineti, M. ; Sapienza, P. ; Schnabel, J. ; Schüssler, F. ; Seitz, T. ; Sieger, C. ; Spurio, M. ; Stolarczyk, Th. ; Sánchez-Losa, A. ; Taiuti, M. ; Trovato, A. ; Tselengidou, M. ; Turpin, D. ; Tönnis, C. ; Vallage, B. ; Vallée, C. ; Van Elewyck, V. ; Vivolo, D. ; Wagner, S. ; Wilms, J. ; Zornoza, J.D. ; Zúñiga, J.
A search for Secluded Dark Matter annihilation in the Sun using 2007-2012 data of the ANTARES neutrino telescope is presented. Three different cases are considered: a) detection of dimuons that result from the decay of the mediator, or neutrino detection from: b) mediator that decays into a dimuon and, in turn, into neutrinos, and c) mediator that decays directly into neutrinos. As no significant excess over background is observed, constraints are derived on the dark matter mass and the lifetime of the mediator.
Adrián-Martínez, S. ; Albert, A. ; André, M. ; Anton, G. ; Ardid, M. ; Aubert, J.-J. ; Avgitas, T. ; Baret, B. ; Barrios-Martí, J. ; Basa, S. ; Bertin, V. ; Biagi, S. ; Bormuth, R. ; Bouwhuis, M.C. ; Bruijn, R. ; Brunner, J. ; Busto, J. ; Capone, A. ; Caramete, L. ; Carr, J. ; Celli, S. ; Chiarusi, T. ; Circella, M. ; Coleiro, A. ; Coniglione, R. ; Costantini, H. ; Coyle, P. ; Creusot, A. ; Deschamps, A. ; De Bonis, G. ; Distefano, C. ; Donzaud, C. ; Dornic, D. ; Drouhin, D. ; Eberl, T. ; El Bojaddaini, I. ; Elsässer, D. ; Enzenhöfer, A. ; Fehn, K. ; Felis, I. ; Fusco, L.A. ; Galatà, S. ; Gay, P. ; Geißelsöder, S. ; Geyer, K. ; Giordano, V. ; Gleixner, A. ; Glotin, H. ; Gracia-Ruiz, R. ; Graf, K. ; Hallmann, S. ; van Haren, H. ; Heijboer, A.J. ; Hello, Y. ; Hernández-Rey, J.J. ; Hößl, J. ; Hofestädt, J. ; Hugon, C. ; Illuminati, G. ; James, C.W. ; de Jong, M. ; Jongen, M. ; Kadler, M. ; Kalekin, O. ; Katz, U. ; Kießling, D. ; Kouchner, A. ; Kreter, M. ; Kreykenbohm, I. ; Kulikovskiy, V. ; Lachaud, C. ; Lahmann, R. ; Lefèvre, D. ; Leonora, E. ; Loucatos, S. ; Marcelin, M. ; Margiotta, A. ; Marinelli, A. ; Martínez-Mora, J.A. ; Mathieu, A. ; Melis, K. ; Michael, T. ; Migliozzi, P. ; Moussa, A. ; Mueller, C. ; Nezri, E. ; Pavalas, G.E. ; Pellegrino, C. ; Perrina, C. ; Piattelli, P. ; Popa, V. ; Pradier, T. ; Racca, C. ; Riccobene, G. ; Roensch, K. ; Saldaña, M. ; Samtleben, D.F.E. ; Sánchez-Losa, A. ; Sanguineti, M. ; Sapienza, P. ; Schnabel, J. ; Schüssler, F. ; Seitz, T. ; Sieger, C. ; Spurio, M. ; Stolarczyk, Th. ; Taiuti, M. ; Tönnis, C. ; Trovato, A. ; Tselengidou, M. ; Turpin, D. ; Vallage, B. ; Vallée, C. ; Van Elewyck, V. ; Vivolo, D. ; Wagner, S. ; Wilms, J. ; Zornoza, J.D. ; Zúñiga, J.
A search for muon neutrinos originating from dark matter annihilations in the Sun is performed using the data recorded by the ANTARES neutrino telescope from 2007 to 2012. In order to obtain the best possible sensitivities to dark matter signals, an optimisation of the event selection criteria is performed taking into account the background of atmospheric muons, atmospheric neutrinos and the energy spectra of the expected neutrino signals. No significant excess over the background is observed and 90% C.L. upper limits on the neutrino flux, the spin-dependent and spin-independent WIMP-nucleon cross-sections are derived for WIMP masses ranging from 50 GeV to 5 TeV for the annihilation channels WIMP + WIMP→ b\(\overline{b}\), W\(^{+}\)W\(^{−}\) and τ\(^{+}\)τ\(^{−}\).
Mining biomedical images towards valuable information retrieval in biomedical and life sciences
(2016)
Biomedical images are helpful sources for the scientists and practitioners in drawing significant hypotheses, exemplifying approaches and describing experimental results in published biomedical literature. In last decades, there has been an enormous increase in the amount of heterogeneous biomedical image production and publication, which results in a need for bioimaging platforms for feature extraction and analysis of text and content in biomedical images to take advantage in implementing effective information retrieval systems. In this review, we summarize technologies related to data mining of figures. We describe and compare the potential of different approaches in terms of their developmental aspects, used methodologies, produced results, achieved accuracies and limitations. Our comparative conclusions include current challenges for bioimaging software with selective image mining, embedded text extraction and processing of complex natural language queries.
Albers, Gregory W. ; Bernstein, Richard A. ; Brachmann, Johannes ; Camm, John ; Easton, J. Donald ; Fromm, Peter ; Goto, Shinya ; Granger, Christopher B. ; Hohnloser, Stefan H. ; Hylek, Elaine ; Jaffer, Amir K. ; Krieger, Derk W. ; Passman, Rod ; Pines, Jesse M. ; Reed, Shelby D. ; Rothwell, Peter M. ; Kowey, Peter R.
An innovative framework has been developed for teamwork of two quadcopter formations, each having its specified formation geometry, assigned task, and matching control scheme. Position control for quadcopters in one of the formations has been implemented through a Linear Quadratic Regulator Proportional Integral (LQR PI) control scheme based on explicit model following scheme. Quadcopters in the other formation are controlled through LQR PI servomechanism control scheme. These two control schemes are compared in terms of their performance and control effort. Both formations are commanded by respective ground stations through virtual leaders. Quadcopters in formations are able to track desired trajectories as well as hovering at desired points for selected time duration. In case of communication loss between ground station and any of the quadcopters, the neighboring quadcopter provides the command data, received from the ground station, to the affected unit. Proposed control schemes have been validated through extensive simulations using MATLAB®/Simulink® that provided favorable results.
A centralized heterogeneous formation flight position control scheme has been formulated using an explicit model following design, based on a Linear Quadratic Regulator Proportional Integral (LQR PI) controller. The leader quadcopter is a stable reference model with desired dynamics whose output is perfectly tracked by the two wingmen quadcopters. The leader itself is controlled through the pole placement control method with desired stability characteristics, while the two followers are controlled through a robust and adaptive LQR PI control method. Selected 3-D formation geometry and static stability are maintained under a number of possible perturbations. With this control scheme, formation geometry may also be switched to any arbitrary shape during flight, provided a suitable collision avoidance mechanism is incorporated. In case of communication loss between the leader and any of the followers, the other follower provides the data, received from the leader, to the affected follower. The stability of the closed-loop system has been analyzed using singular values. The proposed approach for the tightly coupled formation flight of mini unmanned aerial vehicles has been validated with the help of extensive simulations using MATLAB/Simulink, which provided promising results.
Alma, Harma ; de Jong, Corina ; Jelusic, Danijel ; Wittmann, Michael ; Schuler, Michael ; Flokstra-de Blok, Bertine ; Kocks, Janwillem ; Schultz, Konrad ; van der Molen, Thys
The minimal clinically important difference (MCID) defines to what extent change on a health status instrument is clinically relevant, which aids scientists and physicians in measuring therapy effects. This is the first study that aimed to establish the MCID of the Clinical chronic obstructive pulmonary disease (COPD) Questionnaire (CCQ), the COPD Assessment Test (CAT) and the St George’s Respiratory Questionnaire (SGRQ) in the same pulmonary rehabilitation population using multiple approaches. In total, 451 COPD patients participated in a 3-week Pulmonary Rehabilitation (PR) programme (58 years, 65% male, 43 pack-years, GOLD stage II/III/IV 50/39/11%). Techniques used to assess the MCID were anchor-based approaches, including patient-referencing, criterion-referencing and questionnaire-referencing, and the distribution-based methods standard error of measurement (SEM), 1.96SEM and half standard deviation (0.5s.d.). Patient- and criterion-referencing led to MCID estimates of 0.56 and 0.62 (CCQ); 3.12 and 2.96 (CAT); and 8.40 and 9.28 (SGRQ). Questionnaire-referencing suggested MCID ranges of 0.28–0.61 (CCQ), 1.46–3.08 (CAT) and 6.86–9.47 (SGRQ). The SEM, 1.96SEM and 0.5s.d. were 0.29, 0.56 and 0.46 (CCQ); 3.28, 6.43 and 2.80 (CAT); 5.20, 10.19 and 6.06 (SGRQ). Pooled estimates were 0.52 (CCQ), 3.29 (CAT) and 7.91 (SGRQ) for improvement. MCID estimates differed depending on the method used. Pooled estimates suggest clinically relevant improvements needing to exceed 0.40 on the CCQ, 3.00 on the CAT and 7.00 on the SGRQ for moderate to very severe COPD patients. The MCIDs of the CAT and SGRQ in the literature might be too low, leading to overestimation of treatment effects for patients with COPD.
Almanzar, Giovanni ; Klein, Matthias ; Schmalzing, Marc ; Hilligardt, Deborah ; El Hajj, Nady ; Kneitz, Hermann ; Wild, Vanessa ; Rosenwald, Andreas ; Benoit, Sandrine ; Hamm, Henning ; Tony, Hans-Peter ; Haaf, Thomas ; Goebeler, Matthias ; Prelog, Martina
Background: There is much evidence that T cells are strongly involved in the pathogenesis of localized and systemic forms of scleroderma (SSc). A dysbalance between FoxP3+ regulatory CD4+ T cells (Tregs) and inflammatory T-helper (Th) 17 cells has been suggested. Methods: The study aimed (1) to investigate the phenotypical and functional characteristics of Th17 and Tregs in SSc patients depending on disease manifestation (limited vs. diffuse cutaneous SSc, dcSSc) and activity, and (2) the transcriptional level and methylation status of Th17- and Treg-specific transcription factors. Results: There was a concurrent accumulation of circulating peripheral IL-17-producing CCR6+ Th cells and FoxP3+ Tregs in patients with dcSSc. At the transcriptional level, Th17- and Treg-associated transcription factors were elevated in SSc. A strong association with high circulating Th17 and Tregs was seen with early, active, and severe disease presentation. However, a diminished suppressive function on autologous lymphocytes was found in SSc-derived Tregs. Significant relative hypermethylation was seen at the gene level for RORC1 and RORC2 in SSc, particularly in patients with high inflammatory activity. Conclusions: Besides the high transcriptional activity of T cells, attributed to Treg or Th17 phenotype, in active SSc disease, Tregs may be insufficient to produce high amounts of IL-10 or to control proliferative activity of effector T cells in SSc. Our results suggest a high plasticity of Tregs strongly associated with the Th17 phenotype. Future directions may focus on enhancing Treg functions and stabilization of the Treg phenotype.
Alnawaiseh, Maged ; Schubert, Friederike ; Nelis, Pieter ; Wirths, Gabriele ; Rosentreter, André ; Eter, Nicole
Background
Optical coherence tomography angiography is a novel imaging technique that allows dyeless in vivo visualization of the retinal and choroidal vasculature. The purpose of this study was to describe optical coherence tomography (OCT) angiography findings in patients with retinal arterial macroaneurysms (RAMs).
Methods
Three eyes of three patients with RAMs were retrospectively included. Fundus photography, OCT, fluorescein angiography (FA), and OCT angiography were performed. The entire imaging data was analyzed in detail.
Results
OCT angiography could detect the RAMs noninvasively without dye injection. By simultaneously observing the OCT scans, it was possible to determine the depth of the RAMs in the retina, to detect the exact localization in relation to the main vessel, and to determine the level of blood flow in the RAMs.
Conclusions
OCT angiography can clearly visualize RAMs without use of a dye. It also allows layer-specific observation of blood flow in each layer of the RAM. OCT angiography provides additional dynamic information on RAMs, which is not obtained with FA and facilitates a better understanding of its morphology and activity. This information in combination with ICG and fluorescein angiography can help to optimize direct laser treatment.
NFATc1 supports imiquimod-induced skin inflammation by suppressing IL-10 synthesis in B cells
(2016)
Alrefai, Hani ; Muhammad, Khalid ; Rudolf, Ronald ; Pham, Duong Anh Thuy ; Klein-Hessling, Stefan ; Patra, Amiya K. ; Avots, Andris ; Bukur, Valesca ; Sahin,, Ugur ; Tenzer, Stefan ; Goebeler, Matthias ; Kerstan, Andreas ; Serfling, Edgar
Epicutaneous application of Aldara cream containing the TLR7 agonist imiquimod (IMQ) to mice induces skin inflammation that exhibits many aspects of psoriasis, an inflammatory human skin disease. Here we show that mice depleted of B cells or bearing interleukin (IL)-10-deficient B cells show a fulminant inflammation upon IMQ exposure, whereas ablation of NFATc1 in B cells results in a suppression of Aldara-induced inflammation. In vitro, IMQ induces the proliferation and IL-10 expression by B cells that is blocked by BCR signals inducing NFATc1. By binding to HDAC1, a transcriptional repressor, and to an intronic site of the Il10 gene, NFATc1 suppresses IL-10 expression that dampens the production of tumour necrosis factor-α and IL-17 by T cells. These data indicate a close link between NFATc1 and IL-10 expression in B cells and suggest NFATc1 and, in particular, its inducible short isoform, NFATc1/αA, as a potential target to treat human psoriasis.
Anisimov, A. N. ; Simin, D. ; Soltamov, V. A. ; Lebedev, S. P. ; Baranov, P. G. ; Astakhov, G. V. ; Dyakonov, V.
We report a giant thermal shift of 2.1 MHz/K related to the excited-state zero-field splitting in the silicon vacancy centers in 4H silicon carbide. It is obtained from the indirect observation of the optically detected magnetic resonance in the excited state using the ground state as an ancilla. Alternatively, relative variations of the zero-field splitting for small temperature differences can be detected without application of radiofrequency fields, by simply monitoring the photoluminescence intensity in the vicinity of the level anticrossing. This effect results in an all-optical thermometry technique with temperature sensitivity of 100 mK/Hz\(^{1/2}\) for a detection volume of approximately 10\(^{−6}\) mm\(^3\). In contrast, the zero-field splitting in the ground state does not reveal detectable temperature shift. Using these properties, an integrated magnetic field and temperature sensor can be implemented on the same center.
RNA sequencing (RNA-seq) has become a powerful tool to understand molecular mechanisms and/or developmental programs. It provides a fast, reliable and cost-effective method to access sets of expressed elements in a qualitative and quantitative manner. Especially for non-model organisms and in absence of a reference genome, RNA-seq data is used to reconstruct and quantify transcriptomes at the same time. Even SNPs, InDels, and alternative splicing events are predicted directly from the data without having a reference genome at hand. A key challenge, especially for non-computational personnal, is the management of the resulting datasets, consisting of different data types and formats. Here, we present TBro, a flexible de novo transcriptome browser, tackling this challenge. TBro aggregates sequences, their annotation, expression levels as well as differential testing results. It provides an easy-to-use interface to mine the aggregated data and generate publication-ready visualizations. Additionally, it supports users with an intuitive cart system, that helps collecting and analysing biological meaningful sets of transcripts. TBro’s modular architecture allows easy extension of its functionalities in the future. Especially, the integration of new data types such as proteomic quantifications or array-based gene expression data is straightforward. Thus, TBro is a fully featured yet flexible transcriptome browser that supports approaching complex biological questions and enhances collaboration of numerous researchers.
The bis(N-heterocyclic carbene)(diphenylacetylene)palladium complex Pd(ITMe)\(_2\)(PhCCPh)] (ITMe=1,3,4,5-tetramethylimidazol-2-ylidene) acts as a highly active pre-catalyst in the diboration and silaboration of azobenzenes to synthesize a series of novel functionalized hydrazines. The reactions proceed using commercially available diboranes and silaboranes under mild reaction conditions.
Appel, Mirjam ; Scholz, Claus-Jürgen ; Kocabey, Samet ; Savage, Sinead ; König, Christian ; Yarali, Ayse
A painful event establishes two opponent memories: cues that are associated with pain onset are remembered negatively, whereas cues that coincide with the relief at pain offset acquire positive valence. Such punishment-versus relief-memories are conserved across species, including humans, and the balance between them is critical for adaptive behaviour with respect to pain and trauma. In the fruit fly, Drosophila melanogaster as a study case, we found that both punishment-and relief-memories display natural variation across wild-derived inbred strains, but they do not covary, suggesting a considerable level of dissociation in their genetic effectors. This provokes the question whether there may be heritable inter-individual differences in the balance between these opponent memories in man, with potential psycho-clinical implications.
Arimany-Nardi, Cristina ; Minuesa, Gerard ; Pastor-Anglada, Marçal ; Keller, Thorsten ; Erkizia, Itziar ; Koepsell, Hermann ; Martinez-Picado, Javier
Lamivudine (3TC), a drug used in the treatment of HIV infection, needs to cross the plasma membrane to exert its therapeutic action. Human Organic cation transporter 1 (hOCT1), encoded by the SLC22A1 gene, is the transporter responsible for its uptake into target cells. As SLC22A1 is a highly polymorphic gene, the aim of this study was to determine how SNPs in the OCT1-encoding gene affected 3TC internalization and its interaction with other co-administered drugs. HEK293 cells stably transfected with either the wild type form or the polymorphic variants of hOCT1 were used to perform kinetic and drug-drug interaction studies. Protein co-immunoprecipitation was used to assess the impact of selected polymorphic cysteines on the oligomerization of the transporter. Results showed that 3TC transport efficiency was reduced in all polymorphic variants tested (R61C, C88R, S189L, M420del, and G465R). This was not caused by lack of oligomerization in case of variants located at the transporter extracellular loop (R61C and C88R). Drug-drug interaction measurements showed that co-administered drugs [abacavir (ABC), zidovudine (AZT), emtricitabine (FTC), tenofovir diproxil fumarate (TDF), efavirenz (EFV) and raltegravir (RAL)], differently inhibited 3TC uptake depending upon the polymorphic variant analyzed. These data highlight the need for accurate analysis of drug transporter polymorphic variants of clinical relevance, because polymorphisms can impact on substrate (3TC) translocation but even more importantly they can differentially affect drug-drug interactions at the transporter level.
Arrowsmith, Merle ; Böhnke, Julian ; Braunschweig, Holger ; Celik, Mehmet ; Claes, Christina ; Ewing, William ; Krummenacher, Ivo ; Lubitz, Katharina ; Schneider, Christoph
Among the numerous routes organic chemists have developed to synthesize benzene derivatives and heteroaro- matic compounds, transition-metal-catalyzed cycloaddition reactions are the most elegant. In contrast, cycloaddition reactions of heavier alkene and alkyne analogues, though limited in scope, proceed uncatalyzed. In this work we present the first spontaneous cycloaddition reactions of lighter alkene and alkyne analogues. Selective addition of unactivated alkynes to boron–boron multiple bonds under ambient con- ditions yielded diborocarbon equivalents of simple aromatic hydrocarbons, including the first neutral 6p-aromatic dibora- benzene compound, a 2 p-aromatic triplet biradical 1,3-dibor- ete, and a phosphine-stabilized 2 p-homoaromatic 1,3-dihydro- 1,3-diborete. DFT calculations suggest that all three com- pounds are aromatic and show frontier molecular orbitals matching those of the related aromatic hydrocarbons, C6H6 and C4H42+, and homoaromatic C4H5+.