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The Transition Radiation Detector (TRD) was designed and built to enhance the capabilities of the ALICE detector at the Large Hadron Collider (LHC). While aimed at providing electron identification and triggering, the TRD also contributes significantly to the track reconstruction and calibration in the central barrel of ALICE. In this paper the design, construction, operation, and performance of this detector are discussed. A pion rejection factor of up to 410 is achieved at a momentum of 1 GeV/c in p-Pb collisions and the resolution at high transverse momentum improves by about 40% when including the TRD information in track reconstruction. The triggering capability is demonstrated both for jet, light nuclei, and electron selection.
The Transition Radiation Detector (TRD) was designed and built to enhance the capabilities of the ALICE detector at the Large Hadron Collider (LHC). While aimed at providing electron identification and triggering, the TRD also contributes significantly to the track reconstruction and calibration in the central barrel of ALICE. In this paper the design, construction, operation, and performance of this detector are discussed. A pion rejection factor of up to 410 is achieved at a momentum of 1 GeV/c in p-Pb collisions and the resolution at high transverse momentum improves by about 40% when including the TRD information in track reconstruction. The triggering capability is demonstrated both for jet, light nuclei, and electron selection.
The Transition Radiation Detector (TRD) was designed and built to enhance the capabilities of the ALICE detector at the Large Hadron Collider (LHC). While aimed at providing electron identification and triggering, the TRD also contributes significantly to the track reconstruction and calibration in the central barrel of ALICE. In this paper the design, construction, operation, and performance of this detector are discussed. A pion rejection factor of up to 410 is achieved at a momentum of 1 GeV/c in p–Pb collisions and the resolution at high transverse momentum improves by about 40% when including the TRD information in track reconstruction. The triggering capability is demonstrated both for jet, light nuclei, and electron selection.
Previous studies in developing Xenopus and zebrafish reported that the phosphate transporter slc20a1a is expressed in pronephric kidneys. The recent identification of SLC20A1 as a monoallelic candidate gene for cloacal exstrophy further suggests its involvement in the urinary tract and urorectal development. However, little is known of the functional role of SLC20A1 in urinary tract development. Here, we investigated this using morpholino oligonucleotide knockdown of the zebrafish ortholog slc20a1a. This caused kidney cysts and malformations of the cloaca. Moreover, in morphants we demonstrated dysfunctional voiding and hindgut opening defects mimicking imperforate anus in human cloacal exstrophy. Furthermore, we performed immunohistochemistry of an unaffected 6-week-old human embryo and detected SLC20A1 in the urinary tract and the abdominal midline, structures implicated in the pathogenesis of cloacal exstrophy. Additionally, we resequenced SLC20A1 in 690 individuals with bladder exstrophy-epispadias complex (BEEC) including 84 individuals with cloacal exstrophy. We identified two additional monoallelic de novo variants. One was identified in a case-parent trio with classic bladder exstrophy, and one additional novel de novo variant was detected in an affected mother who transmitted this variant to her affected son. To study the potential cellular impact of SLC20A1 variants, we expressed them in HEK293 cells. Here, phosphate transport was not compromised, suggesting that it is not a disease mechanism. However, there was a tendency for lower levels of cleaved caspase-3, perhaps implicating apoptosis pathways in the disease. Our results suggest SLC20A1 is involved in urinary tract and urorectal development and implicate SLC20A1 as a disease-gene for BEEC.
Microangiopathy with subsequent organ damage represents a major complication in several diseases. The mechanisms leading to microvascular occlusion include von Willebrand factor (VWF), notably the formation of ultra-large von Willebrand factor fibers (ULVWFs) and platelet aggregation. To date, the contribution of erythrocytes to vascular occlusion is incompletely clarified. We investigated the platelet-independent interaction between stressed erythrocytes and ULVWFs and its consequences for microcirculation and organ function under dynamic conditions. In response to shear stress, erythrocytes interacted strongly with VWF to initiate the formation of ULVWF/erythrocyte aggregates via the binding of Annexin V to the VWF A1 domain. VWF-erythrocyte adhesion was attenuated by heparin and the VWF-specific protease ADAMTS13. In an in vivo model of renal ischemia/reperfusion injury, erythrocytes adhered to capillaries of wild-type but not VWF-deficient mice and later resulted in less renal damage. In vivo imaging in mice confirmed the adhesion of stressed erythrocytes to the vessel wall. Moreover, enhanced eryptosis rates and increased VWF binding were detected in blood samples from patients with chronic renal failure. Our study demonstrates that stressed erythrocytes have a pronounced binding affinity to ULVWFs. The discovered mechanisms suggest that erythrocytes are essential for the pathogenesis of microangiopathies and renal damage by actively binding to ULVWFs.
Background While there is enough convincing evidence in childhood acute lymphoblastic leukemia (ALL), the data on the pre-natal origin in childhood acute myeloid leukemia (AML) are less comprehensive. Our study aimed to screen Guthrie cards (neonatal blood spots) of non-infant childhood AML and ALL patients for the presence of their respective leukemic markers. Methods We analysed Guthrie cards of 12 ALL patients aged 2–6 years using immunoglobulin (Ig) and T-cell receptor (TCR) gene rearrangements (n = 15) and/or intronic breakpoints of TEL/AML1 fusion gene (n = 3). In AML patients (n = 13, age 1–14 years) PML/RARalpha (n = 4), CBFbeta/MYH11 (n = 3), AML1/ETO (n = 2), MLL/AF6 (n = 1), MLL/AF9 (n = 1) and MLL/AF10 (n = 1) fusion genes and/or internal tandem duplication of FLT3 gene (FLT3/ITD) (n = 2) were used as clonotypic markers. Assay sensitivity determined using serial dilutions of patient DNA into the DNA of a healthy donor allowed us to detect the pre-leukemic clone in Guthrie card providing 1–3 positive cells were present in the neonatal blood spot. Results In 3 patients with ALL (25%) we reproducibly detected their leukemic markers (Ig/TCR n = 2; TEL/AML1 n = 1) in the Guthrie card. We did not find patient-specific molecular markers in any patient with AML. Conclusion In the largest cohort examined so far we used identical approach for the backtracking of non-infant childhood ALL and AML. Our data suggest that either the prenatal origin of AML is less frequent or the load of pre-leukemic cells is significantly lower at birth in AML compared to ALL cases.
The last decade has seen a sharp increase in the number of scientific publications describing physiological and pathological functions of extracellular vesicles (EVs), a collective term covering various subtypes of cell-released, membranous structures, called exosomes, microvesicles, microparticles, ectosomes, oncosomes, apoptotic bodies, and many other names. However, specific issues arise when working with these entities, whose size and amount often make them difficult to obtain as relatively pure preparations, and to characterize properly. The International Society for Extracellular Vesicles (ISEV) proposed Minimal Information for Studies of Extracellular Vesicles (“MISEV”) guidelines for the field in 2014. We now update these “MISEV2014” guidelines based on evolution of the collective knowledge in the last four years. An important point to consider is that ascribing a specific function to EVs in general, or to subtypes of EVs, requires reporting of specific information beyond mere description of function in a crude, potentially contaminated, and heterogeneous preparation. For example, claims that exosomes are endowed with exquisite and specific activities remain difficult to support experimentally, given our still limited knowledge of their specific molecular machineries of biogenesis and release, as compared with other biophysically similar EVs. The MISEV2018 guidelines include tables and outlines of suggested protocols and steps to follow to document specific EV-associated functional activities. Finally, a checklist is provided with summaries of key points.
Non-standard errors
(2021)
In statistics, samples are drawn from a population in a data-generating process (DGP). Standard errors measure the uncertainty in sample estimates of population parameters. In science, evidence is generated to test hypotheses in an evidence-generating process (EGP). We claim that EGP variation across researchers adds uncertainty: non-standard errors. To study them, we let 164 teams test six hypotheses on the same sample. We find that non-standard errors are sizeable, on par with standard errors. Their size (i) co-varies only weakly with team merits, reproducibility, or peer rating, (ii) declines significantly after peer-feedback, and (iii) is underestimated by participants.
Nicht zuletzt durch die Entwicklung und Verbreitung der sogenannten Neuen Medien ist das Thema 'Medialität' im gesamten Bereich der Geistes- und Kulturwissenschaften virulent geworden. Im Rahmen der aktuellen Diskurse um den Begriff des Mediums ist zu beobachten, daß dieser Ausdruck häufig unterschiedslos auf so verschiedene Referenzobjekte wie Internet, Fernsehen, Printmedien, Computer, Schrift, Bilder, Schallwellen u. v. a. bezogen wird. Das Medium orale Sprache gerät dabei sonderbarerweise häufig aus dem Blickfeld. - Warum ist dies so?
Woher kommt das neuerwachte Interesse an Sprachrichtigkeit? Woher kommt die ausgeprägte sprachliche Unsicherheit, die auch bei vielen hochgebildeten Menschen den Wunsch entstehen lässt, von Sprachpflegern über ihr Ureigenstes, nämlich ihre Muttersprache, belehrt zu werden? Obwohl Antworten auf diese Fragen letztlich spekulativ bleiben, wage ich doch die These, dass eine Ursache hierfür die Rechtschreibreform ist, die von einem Großteil der Bevölkerung nach wie vor nicht angenommen wird, die insgesamt weder zur Vereinfachung noch zu einer höheren Einheitlichkeit geführt hat; die aber andererseits ein öffentliches Nachdenken und Diskutieren über Sprachrichtigkeit in Gang setzte. – Jedenfalls ist die Verunsicherung ein Faktum, das von Linguisten nicht ignoriert werden sollte.
Ausgangspunkt: Die Kritik am "Zwei-Welten-Modell": Die grundlegende linguistische Unterscheidung zwischen "Sprache" und "Sprechen" ist im Rahmen der neueren Debatten um Sprachmedialität wieder verstärkt thematisiert und kritisiert worden. Lässt sich dieses schulbildende, in der Linguistik geradezu eherne Begriffspaar überhaupt noch sinnvollerweise aufrechterhalten? Oder muss es mindestens umdefiniert, vielleicht sogar gänzlich verworfen werden? Hat sich insbesondere die auf Chomsky zurückgehende Unterscheidung von Sprachkompetenz und -performanz nicht von selbst ad absurdum geführt, nachdem der linguistische Kognitivismus chomskyscher Provenienz Sprache als lebendiges Phänomen, als Medium menschlicher Kommunikation, vollständig aus dem Blick verloren hat? Führt nicht schon die scheinbar harmlose linguistische Differenzierung zwischen einer Sprachregel und ihrer Anwendung zu einer irreführenden und unangemessenen Verdinglichung von Sprache? ...
Ziel des vorliegenden Aufsatzes ist es, zu einer neuerlichen Diskussion der Begriffe 'Medium' und 'Kommunikation' in der Linguistik beizutragen. Dabei versuche ich insbesondere, den philosophisch-kulturwissenschaftlichen Diskurs, in welchem die Themen 'Medialität' und 'Perfonnanz' seit längerer Zeit intensiv diskutiert werden, zu dem in der Angewandten Linguistik geläufigen Modell der Kommunikationsformen in Beziehung zu setzen und Möglichkeiten einer Verbindung dieser beiden Diskurse zumindest anzudeuten. Der Aufsatz gliedert sich in vier Abschnitte: Zunächst werden einige geläufige Mediendefinitionen vorgestellt. Im zweiten Kapitel stelle ich dann die Frage 'Ist Kommunikation ein Transportvorgang?', um auf dieser Grundlage im dritten Kapitel eine alternative Medienkonzeption vorzustellen. Im letzten Kapitel wird dieser Medienbegriff dann sowohl vom Begriff des Zeichensystems, als auch von dem der Kommunikationsform abgegrenzt.
The medium of (oral) language is mostly disregarded (or overlooked) in contemporary media theories. This "ignoring of language" in media studies is often accompanied by an inadequate transport model of communication, and it converges with an "ignoring of mediality" in mentalistic theories of language. In the present article it will be argued that this misleading opposition of language and media can only be overcome if one already regards oral language, not just written language, as a medium of the human mind. In my argumentation I fall back on Wittgenstein’s conception of language games to try to show how Wittgenstein’s ideas can help us to clear up the problem of the mediality of language and also to show to what extent the mentalistic conception of Chomskyan provenance cannot be adequate to the phenomenon of language.
Die Themen Sprachrichtigkeit und Sprachidentität haben in Deutschland seit einiger Zeit Hochkonjunktur. Der 'Sprachpfleger' Bastian Sick, in der massenmedialen Berichterstattung stereotyp als gleichermaßen "kompetent" wie "lustig" und "gar nicht oberlehrerhaft" angepriesen, verkauft seine Kolumnensammlungen millionenfach und füllt bei seinen Lesungen mühelos ganze Konzertsäle. Der Verein Deutsche Sprache, Speerspitze der Anglizismenkritik im deutschsprachigen Raum, hat nach eigenen Angaben mittlerweile fast 30.000 Mitglieder. Betrachtet man diese Protagonisten des öffentlichen Sprachdiskurses aus linguistischer Perspektive, so stellt man fest, dass sich die von ihnen propagierte Sprachauffassung in der Regel an einer alten Metapher orientiert – der biologistischen Metapher von Sprache als einem Organismus: Ein Organismus kann geboren werden und sterben; er kann krank werden und verfallen, er ist – um es mit einem Ausdruck von Jürgen Spitzmüller zu sagen – eine klar "abgrenzbare Einheit". Ein Sprachsystem erscheint somit als ein abgeschlossenes organisches Gebilde, welches es zu erhalten gilt und das durch schädliche Einflüsse von außen in seiner Identität gefährdet ist.
Sprache als kranker Organismus : linguistische Anmerkungen zum Spiegel-Titel "Rettet dem Deutsch!"
(2007)
In the present article we argue that all communication is medial in the sense that every human sign-based interaction is shaped by medial aspects from the outset. We propose a dynamic, semiotic concept of media that focuses on the process-related aspect of mediality, and we test the applicability of this concept using as an example the second presidential debate between Clinton and Trump in 2016. The analysis shows in detail how the sign processing during the debate is continuously shaped by structural aspects of television and specific traits of political communication in television. This includes how the camerawork creates meaning and how the protagonists both use the affordances of this special mediality. Therefore, it is not adequate in our view to separate the technical aspects of the medium, the ‘hardware’, from the processual aspects and the structural conditions of communication. While some aspects of the interaction are directly constituted by the medium, others are more indirectly shaped and influenced by it, especially by its institutional dimension – we understand them as second-order media effects. The whole medial procedure with its specific mediality is a necessary, but not a sufficient condition of meaning-making. We distinguish the medial procedure from the semiotic modes employed, the language games played and the competence of the players involved.
Dancing is an activity that positively enhances the mood of people that consists of feeling the music and expressing it in rhythmic movements with the body. Learning how to dance can be challenging because it requires proper coordination and understanding of rhythm and beat. In this paper, we present the first implementation of the Dancing Coach (DC), a generic system designed to support the practice of dancing steps, which in its current state supports the practice of basic salsa dancing steps. However, the DC has been designed to allow the addition of more dance styles. We also present the first user evaluation of the DC, which consists of user tests with 25 participants. Results from the user test show that participants stated they had learned the basic salsa dancing steps, to move to the beat and body coordination in a fun way. Results also point out some direction on how to improve the future versions of the DC.
The development of multimodal sensor-based applications designed to support learners with the improvement of their skills is expensive since most of these applications are tailor-made and built from scratch. In this paper, we show how the Presentation Trainer (PT), a multimodal sensor-based application designed to support the development of public speaking skills, can be modularly extended with a Virtual Reality real-time feedback module (VR module), which makes usage of the PT more immersive and comprehensive. The described study consists of a formative evaluation and has two main objectives. Firstly, a technical objective is concerned with the feasibility of extending the PT with an immersive VR Module. Secondly, a user experience objective focuses on the level of satisfaction of interacting with the VR extended PT. To study these objectives, we conducted user tests with 20 participants. Results from our test show the feasibility of modularly extending existing multimodal sensor-based applications, and in terms of learning and user experience, results indicate a positive attitude of the participants towards using the application (PT+VR module).
Learning to solve graph tasks is one of the key prerequisites of acquiring domain-specific knowledge in most study domains. Analyses of graph understanding often use eye-tracking and focus on analyzing how much time students spend gazing at particular areas of a graph—Areas of Interest (AOIs). To gain a deeper insight into students’ task-solving process, we argue that the gaze shifts between students’ fixations on different AOIs (so-termed transitions) also need to be included in holistic analyses of graph understanding that consider the importance of transitions for the task-solving process. Thus, we introduced Epistemic Network Analysis (ENA) as a novel approach to analyze eye-tracking data of 23 university students who solved eight multiple-choice graph tasks in physics and economics. ENA is a method for quantifying, visualizing, and interpreting network data allowing a weighted analysis of the gaze patterns of both correct and incorrect graph task solvers considering the interrelations between fixations and transitions. After an analysis of the differences in the number of fixations and the number of single transitions between correct and incorrect solvers, we conducted an ENA for each task. We demonstrate that an isolated analysis of fixations and transitions provides only a limited insight into graph solving behavior. In contrast, ENA identifies differences between the gaze patterns of students who solved the graph tasks correctly and incorrectly across the multiple graph tasks. For instance, incorrect solvers shifted their gaze from the graph to the x-axis and from the question to the graph comparatively more often than correct solvers. The results indicate that incorrect solvers often have problems transferring textual information into graphical information and rely more on partly irrelevant parts of a graph. Finally, we discuss how the findings can be used to design experimental studies and for innovative instructional procedures in higher education
The representation of small molecules as molecular graphs is a common technique in various fields of cheminformatics. This approach employs abstract descriptions of topology and properties for rapid analyses and comparison. Receptor-based methods in contrast mostly depend on more complex representations impeding simplified analysis and limiting the possibilities of property assignment. In this study we demonstrate that ligand-based methods can be applied to receptor-derived binding site analysis. We introduce the new method PocketGraph that translates representations of binding site volumes into linear graphs and enables the application of graph-based methods to the world of protein pockets. The method uses the PocketPicker algorithm for characterization of binding site volumes and employs a Growing Neural Gas procedure to derive graph representations of pocket topologies. Self-organizing map (SOM) projections revealed a limited number of pocket topologies. We argue that there is only a small set of pocket shapes realized in the known ligand-receptor complexes.