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The detection of cortical malformations in conventional MR images can be challenging. Prominent examples are focal cortical dysplasias (FCD), the most common cause of drug‐resistant focal epilepsy. The two main MRI hallmarks of cortical malformations are increased cortical thickness and blurring of the gray (GM) and white matter (WM) junction. The purpose of this study was to derive synthetic anatomies from quantitative T1 maps for the improved display of the above imaging characteristics in individual patients.
On the basis of a T1 map, a mask comprising pixels with T1 values characteristic for GM is created from which the local cortical extent (CE) is determined. The local smoothness (SM) of the GM‐WM junctions is derived from the T1 gradient. For display of cortical malformations, the resulting CE and SM maps serve to enhance local intensities in synthetic double inversion recovery (DIR) images calculated from the T1 map.
The resulting CE‐ and/or SM‐enhanced DIR images appear hyperintense at the site of cortical malformations, thus facilitating FCD detection in epilepsy patients. However, false positives may arise in areas with naturally elevated CE and/or SM, such as large GM structures and perivascular spaces.
In summary, the proposed method facilitates the detection of cortical abnormalities such as cortical thickening and blurring of the GM‐WM junction which are typical FCD markers. Still, subject motion artifacts, perivascular spaces, and large normal GM structures may also yield signal hyperintensity in the enhanced synthetic DIR images, requiring careful comparison with clinical MR images by an experienced neuroradiologist to exclude false positives.
Signal transduction and the regulation of gene expression are fundamental processes in every cell. RNA-binding proteins (RBPs) play a key role in the post-transcriptional modulation of gene expression in response to both internal and external stimuli. However, how signaling pathways regulate the assembly of RBPs with mRNAs remains largely unknown. Here, we summarize observations showing that the formation and composition of messenger ribonucleoprotein particles (mRNPs) is dynamically remodeled in space and time by specific signaling cascades and the resulting post-translational modifications. The integration of signaling events with gene expression is key to the rapid adaptation of cells to environmental changes and stress. Only a combined approach analyzing the signal transduction pathways and the changes in post-transcriptional gene expression they cause will unravel the mechanisms coordinating these important cellular processes.
Postoperative thrombotic thrombocytopenic purpura (TTP) shows clinical presentation similar to classical TTP, whereas exact pathophysiological contexts remain unexplained. In this study, we investigated intraoperative and postoperative changes in ADAMTS-13 (a disintegrin and metalloprotease with thrombospondin type 1 motifs, member 13), von Willebrand factor (VWF), large VWF multimers, and interleukin-6 (IL-6) in vascular surgery patients. The objective was to compare the impact of endovascular, peripheral, and aortic surgery on target parameters which are supposed to play a role in surgery-associated TTP. A total of 93 vascular surgery patients were included and divided into 4 groups according to the specific type of intervention they underwent. Blood samples were taken preoperatively, intraoperatively, and postoperatively on days 2 and 4. The ADAMTS-13 activity decreased significantly in 3 of the 4 groups during surgery (from median 81% to 49%, P < .001, in the group undergoing aortoiliacal interventions), whereas the percentage of large VWF multimers increased in all groups of patients. von Willebrand factor antigen increased significantly in all groups on postoperative day 2 and IL-6 increased significantly in the intraoperative and early postoperative period. There was no significant correlation between the intraoperative decrease in ADAMTS-13 and the increase in VWF or IL-6. No patient in this study showed clinical picture of TTP; the precise cause and clinical significance of moderately reduced ADAMTS-13 activity in the perioperative setting have not yet been definitely determined.
Background: Macrophage Migration Inhibitory Factor (MIF) is highly elevated after cardiac surgery and impacts the postoperative inflammation. The aim of this study was to analyze whether the polymorphisms CATT5–7 (rs5844572/rs3063368,“-794”) and G>C single-nucleotide polymorphism (rs755622,-173) in the MIF gene promoter are related to postoperative outcome. Methods: In 1116 patients undergoing cardiac surgery, the MIF gene polymorphisms were analyzed and serum MIF was measured by ELISA in 100 patients. Results: Patients with at least one extended repeat allele (CATT7) had a significantly higher risk of acute kidney injury (AKI) compared to others (23% vs. 13%; OR 2.01 (1.40–2.88), p = 0.0001). Carriers of CATT7 were also at higher risk of death (1.8% vs. 0.4%; OR 5.12 (0.99–33.14), p = 0.026). The GC genotype was associated with AKI (20% vs. GG/CC:13%, OR 1.71 (1.20–2.43), p = 0.003). Multivariate analyses identified CATT7 predictive for AKI (OR 2.13 (1.46–3.09), p < 0.001) and death (OR 5.58 (1.29–24.04), p = 0.021). CATT7 was associated with higher serum MIF before surgery (79.2 vs. 50.4 ng/mL, p = 0.008). Conclusion: The CATT7 allele associates with a higher risk of AKI and death after cardiac surgery, which might be related to chronically elevated serum MIF. Polymorphisms in the MIF gene may constitute a predisposition for postoperative complications and the assessment may improve risk stratification and therapeutic guidance.
Simple Summary: Glioblastomas are very malignant and essentially incurable brain tumors. One problem is the extensive penetration of tumor cells into the adjacent normal brain tissue. Thus, the testing of novel drugs requires appropriate tumor models, preferentially avoiding animal studies. This paper describes so-called brain tissue slice tandem-culture systems. They consist of a slice of normal brain tissue and a second layer of tumor tissue. The microscopic analysis of these slice tandem-cultures allows for the simultaneous assessment of single cells invading into the normal brain tissue and the space occupying growth of the total tumor mass. It is shown that the direct application of test drugs onto the slices exerts inhibitory effects on both mechanisms. We thus describe a system mimicking the situation in glioblastoma patients. It reduces animal studies, allows for the direct application of test drugs and the precise quantitation of their inhibitory effects on tumor growth and invasion.
Abstract: Glioblastomas (GBMs) are the most malignant brain tumors and are essentially incurable even after extensive surgery, radiotherapy, and chemotherapy, mainly because of extensive infiltration of tumor cells into the adjacent normal tissue. Thus, the evaluation of novel drugs in malignant glioma treatment requires sophisticated ex vivo models that approach the authentic interplay between tumor and host environment while avoiding extensive in vivo studies in animals. This paper describes the standardized setup of an organotypic brain tissue slice tandem-culture system, comprising of normal brain tissue from adult mice and tumor tissue from human glioblastoma xenografts, and explore its utility for assessing inhibitory effects of test drugs. The microscopic analysis of vertical sections of the slice tandem-cultures allows for the simultaneous assessment of (i) the invasive potential of single cells or cell aggregates and (ii) the space occupying growth of the bulk tumor mass, both contributing to malignant tumor progression. The comparison of tissue slice co-cultures with spheroids vs. tissue slice tandem-cultures using tumor xenograft slices demonstrates advantages of the xenograft tandem approach. The direct and facile application of test drugs is shown to exert inhibitory effects on bulk tumor growth and/or tumor cell invasion, and allows their precise quantitation. In conclusion, we describe a straightforward ex vivo system mimicking the in vivo situation of the tumor mass and the normal brain in GBM patients. It reduces animal studies and allows for the direct and reproducible application of test drugs and the precise quantitation of their effects on the bulk tumor mass and on the tumor’s invasive properties
In this paper we deal with an implementation as well as numerical experiments for the coupling of interior and exterior problems of the elastodynamic wave equation with transparent boundary conditions in 3D as described in a previous paper by this author. In more detail, the FEM‐BEM‐coupling as well as the time discretization by using leapfrog and convolution quadrature is considered. Our aim is to provide an insight into the necessary steps of the implementation. Based on this, we present numerical experiments for a non‐convex domain and analyze the errors.
Progression of pupil dilation (PD) in response to visual stimuli may indicate distinct internal processes. No study has been performed on PD progression during a social cognition task. Here, we describe PD progression during the Movie for the Assessment of Social Cognition (MASC) test in n = 23 adolescents with Autism Spectrum Disorder (ASD) and n = 24 age, IQ and sex‐matched neurotypical controls (NTC). The MASC consists of 43 video sequences depicting human social interactions, each followed by a multiple‐choice question concerning characters' mental states. PD progression data were extracted by eye tracking and controlled for fixation behavior. Segmenting PD progression during video sequences by principal component analysis, three sequential PD components were unveiled. In ASD compared with NTC, a distinct PD progression was observed with increased constriction amplitude, increased dilation latency, and increased dilation amplitude that correlated with PD progression components. These components predicted social cognition performance. The first and second PD components correlated positively with MASC behavioral performance in ASD but negatively in NTC. These PD components may be interpreted as indicators of sensory‐perceptual processing and attention function. In ASD, aberrant sensory‐perceptual processing and attention function could contribute to attenuated social cognition performance. This needs to be tested by additional studies combining the respective cognitive tests and the outlined PD progression analysis. Phasic activity of the locus coeruleus–norepinephrine system is discussed as putatively shared underlying mechanism.
This thesis investigates the acquisition pace and the typical developmental path in eL2 acquisition of selected phenomena of German morphosyntax and semantics and compared them to monolingual acquisition. In addition, the influence of ‘Age of Onset’ and of external factors on eL2 acquisition is examined.
To date, the most studies on eL2 acquisition focused on language production. Based on mostly longitudinal spontaneous speech data of only small number of children, they indicate that eL2 learners acquire sentence structure and subject-verb-agreement faster than monolingual children, whereas the acquisition of case marking causes them more difficulties. Moreover, similar developmental paths to those of monolingual children are claimed. Only several studies examined comprehension abilities in eL2 learners, however overwhelmingly in cross-sectional design. The findings from comprehension studies on telic and atelic verbs, and on wh-questions indicate that eL2 children acquire their target-like interpretation faster than monolingual children. The same acquisition stages towards target-like interpretation like in monolingual acquisition are assumed as well. Taking together, to date, no study exists, that examines comprehension and production abilities in a large group of eL2 learners of German in a longitudinal design.
This thesis extends the previous results by investigating pace of acquisition, impact of factors, and individual developmental paths in a longitudinal design with large groups of participants. Language data of 29 eL2 learners of German (age at T1: 3;7 years, LoE: 10 months) and 45 monolingual German-speaking children (age at T1: 3;7) are examined. The eL2 learners were tested in six test rounds (age at T6: 6;9 years). The monolingual children were tested in five test rounds (are at T5: 5;7). The standardized test LiSe-DaZ (Schulz & Tracy, 2011) was employed to examine children’s language skills.
eL2 learners show a significantly greater rate of change, thus faster acquisition pace, than monolingual children in the following scales: comprehension of telicity, comprehension of wh-questions, production of prepositions, and production of conjunctions. These phenomena are acquired early in monolingual children. No differences regarding acquisition pace between eL2 children and monolingual children are found for comprehension of negation, production of case marking, and production of focus particles. These phenomena are acquired late in monolingual development and involve semantic and pragmatic knowledge. The findings of faster acquisition pace of several phenomena are in line with several studies that reported that eL2 children develop faster than monolingual children.
Independent on whether a phenomenon is acquired early or late, no effects of external factors on eL2 children’s performance are found. These findings indicate that acquisition of core, rule-based phenomena is not sensitive to external factors if the first exposure to L2 takes place around the age of three.
Moreover, eL2 children show the same developmental stages and error types in comprehension of telicity, comprehension of negation, production of matrix and subordinate clauses. This is also independent on how fast they acquire a structure under consideration. Thus, these findings provide a further support for similar developmental paths of eL2 and monolingual children towards target-like comprehension and production.
Stanley Cavell is one of very few philosophers who systematically reflect on the impact and influence of autobiographical detail, experience, and preferences on their philosophical work. The aim of this essay is to show how Cavell’s use of autobiographical exploration is rooted in his early aesthetic theory, in particular his view of the similarities between philosophy and aesthetic criticism. Cavell argues that criticism starts by exploiting and incorporating a subjective vantage point, eventually bringing the reader to test the significance of a work on herself. In his ‘Aesthetic Problems of Modern Philosophy’, Cavell states exactly this form of appeal to the ‘We’ of author and reader as the basic move of his own version of ‘ordinary language philosophy’. It is because of the connections Cavell sees between criticism and philosophy that his aesthetic diagnosis harks back on his overall critical style of thinking.
The strictly anaerobic acetogenic bacterium Acetobacterium woodii is metabolically diverse and grows on variety of substrates which includes H2 + CO2, sugars, alcohols and diols. It is unique in producing bacterial microcompartments (BMC) during growth on different substrates such as 1,2-propanediol, 2,3-butanediol, ethanol or fructose. In this study, we analyzed the genetic organization and expression of the BMC genes within the A. woodii genome, the previously described 18 gene pdu cluster as well as four other cluster potentially encoding one or two shell proteins. Expression analysis of respective gene clusters revealed that the pdu gene cluster is highly expressed during growth on 1,2-PD, 2,3-BD, ethanol and ethylene glycol. The promoter region upstream of the pduA gene was identified and used to establish a reporter gene assay based on chloramphenicol acetyl transferase as a reporter protein. The reporter gene assay confirmed the qPCR data and demonstrated that 1,2-PD is superior over ethanol and ethylene glycol as inducer. BMCs were enriched from cells grown on 2,3- BD and 1,2-PD and shown to have typical structure in electron micrographs. Biochemical analyses revealed several of the protein encoded by the pdu cluster to be part of the isolated BMCs. These data demonstrate a very unique situation in A. woodii in which apparently one BMC gene cluster in expressed during growth on different substrates.
Background: Balloon pulmonary angioplasty is an evolving, interventional treatment option for inoperable patients with chronic thromboembolic pulmonary hypertension (CTEPH). Pulmonary hypertension at rest as well as exercise capacity is considered to be relevant outcome parameters. The aim of the present study was to determine whether measurement of pulmonary hemodynamics during exercise before and six months after balloon pulmonary angioplasty have an added value.
Methods: From March 2014 to July 2018, 172 consecutive patients underwent balloon pulmonary angioplasty. Of these, 64 consecutive patients with inoperable CTEPH underwent a comprehensive diagnostic workup that included right heart catheterization at rest and during exercise before balloon pulmonary angioplasty treatments and six months after the last intervention.
Results: Improvements in pulmonary hemodynamics at rest and during exercise, in quality of life, and in exercise capacity were observed six months after balloon pulmonary angioplasty: WHO functional class improved in 78% of patients. The mean pulmonary arterial pressure (mPAP) at rest was reduced from 41 ± 9 to 31 ± 9 mmHg (p < 0.0001). The mPAP/cardiac output slope decreased after balloon pulmonary angioplasty (11.2 ± 25.6 WU to 7.7 ± 4.1 WU; p < 0.0001), and correlated with N-terminal fragment of pro-brain natriuretic peptide (p = 0.035) and 6-minute walking distance (p = 0.01).
Conclusions: Exercise right heart catheterization provides valuable information on the changes of pulmonary hemodynamics after balloon pulmonary angioplasty in inoperable CTEPH patients that are not obtainable by measuring resting hemodynamics.
Resistance exercise has been demonstrated to improve brain function. However, the optimal workout characteristics are a matter of debate. This randomized, controlled trial aimed to elucidate differences between free-weight (REfree) and machine-based (REmach) training with regard to their ability to acutely enhance cognitive performance (CP). A total of n = 46 healthy individuals (27 ± 4 years, 26 men) performed a 45-min bout of REfree (military press, barbell squat, bench press) or REmach (shoulder press, leg press, chest press). Pre- and post-intervention, CP was examined using the Stroop test, Trail Making Test and Digit Span test. Mann–Whitney U tests did not reveal between-group differences for performance in the Digit Span test, Trail Making test and the color and word conditions of the Stroop test (p > 0.05). However, REfree was superior to REmach in the Stroop color-word condition (+6.3%, p = 0.02, R = 0.35). Additionally, REfree elicited pre-post changes in all parameters except for the Digit Span test and the word condition of the Stroop test while REmach only improved cognitive performance in part A of the Trail Making test. Using free weights seems to be the more effective RE method to acutely improve cognitive function (i.e., inhibitory control). The mechanisms of this finding merit further investigation.
Obstructive Sleep Apnea is emerging as a global health epidemic, particularly due to the obesity pandemic. However, comprehensive prevalence data are still lacking and global OSA research has not yet been structurally evaluated. Using the latest comprehensive age/gender-specific BMI and obesity data, a global landscape estimating the risk/burden of OSA was created. Results were presented in relation to an in-depth analysis of OSA research and countries’ socioeconomic/scientific background. While the USA, Canada, and Japan are the highest publishing countries on OSA, Iceland, Greece, and Israel appeared at the forefront when relating the scientific output to socioeconomic parameters. Conversely, China, India, and Russia showed relatively low performances in these relations. Analysis of the estimated population at risk (EPR) of OSA showed the USA, China, India, and Brazil as the leading countries. Although the EPR and OSA research correlated strongly, major regional discrepancies between the estimated demand and actual research performances were identified, mainly in, but not limited to, developing nations. Our study highlights regional challenges/imbalances in the global activity on OSA and allows targeted measures to mitigate the burden of undiagnosed/untreated OSA. Furthermore, the inclusion of disadvantaged countries in international collaborations could stimulate local research efforts and provide valuable insights into the regional epidemiology of OSA.
Four main informational elements have been suggested and studied as central aspects of narrative discourse: causality, character, location, time. The research that scholars have previously undertaken on these aspects has been primarily on Indo-European languages, and more specifically on the European side of that language family. The linguistic limitations have indicated that character is the aspect of narrative that readers/listeners attend to most closely. However, in examining narrative discourses from non-Indo-European languages, challenges to the presumed primacy of character emerge. In a partial report on field work conducted in Borneo in 2012-2015, I compare and contrast patterns in the rankings of the four main aspects of narrative in three languages, English, Hobongan and Daqan. I also note the strategies by which the languages make their respective rankings clear, including focus particles (Hobongan), specificity of description (each), and amount of information provided about the aspects (each). I suggest that analyses of the patterns and rankings of information in narrative be included in typological categorizations and linguistic descriptions of languages.
Objective: to systematize the strengths and challenges of Axel Honneth’s Theory of Recognition, and to reflect on these as support for research in health care. Method: this is a reflection article which considers the potential of incorporating the category of recognition in the Honnethian proposition for research, understanding, exercising of practice and management of health care. Results: the process of recognition promotes the exploration and understanding of relations of power and respect, above all in terms of conflict which are ascribed to these. As a result, it indicates support for diagnoses and structuring nuclei for overcoming oppressive and unequal practices, with consequences for dealing with situations of insecurity, weaknesses in self-esteem and vulnerabilities in the interactions between the subjects, which are configured as contemporary challenges. Conclusion: in the scientific exploration of care, management and public policies in health, this theoretical framework can assist in the visibility of the context and in its critical knots, in order to promote autonomy and human dignity, which are relevant for the interpersonal relations in the processes of care, with fruitful contributions to the qualification of the health care.
From reciprocal recognition to a society that is properly 'social' : on Axel Honneth's recent work
(2017)
This paper addresses Axel Honneth's recent endeavors to defend his theory of justice, broadly described in Freedom's right (2011) as an analysis of society. The paper begins by exposing Honneth's model as a theory of institutional intersubjectivity rather than a theory of the struggle for recognition. This model, however, was subject to criticism due to its supposed acceptance of the capitalistic market economy as a social order. In order to defend it from such objections, Honneth (2016) exposes the normative core of socialist ideals as a version of social freedom. Finally, he presents a distinction between two forms of political intervention: an internal and an external struggle for recognition – and asserts the advantages of the former.
Space optimizations in deterministic and concurrent call-by-need functional programming languages
(2020)
In this thesis the space consumption and runtime of lazy-evaluating functional programming languages are analyzed.
The typed and extended lambda-calculi LRP and CHF* as core languages for Haskell and Concurrent Haskell are used. For each LRP and CHF* compatible abstract machines are introduced.
Too lower the distortion of space measurement a classical implementable garbage collector is applied after each LRP reduction step. Die size of expressions and the space measure spmax as maximal size of all garbage-free expressions during an LRP-evaluation, are defined.
Program-Transformations are considered as code-to-code transformations. The notions Space Improvement and Space Equivalence as properties of transformations are defined. A Space Improvement does neither change the semantics nor it increases the needed space consumption, for a space equivalence the space consumption is required to remain the same. Several transformations are shown as Space Improvements and Equivalences.
An abstract machine for space measurements is introduced. An implementation of this machine is used for more complex space- and runtime-analyses.
Total Garbage Collection replaces subexpressions by a non-terminating constant with size zero, if the overall termination is not affected. Thereby the notion of improvement is more independent from the used garbage collector.
Analogous to Space Improvements and Equivalences the notions Total Space Improvement and Total Space Equivalence are defined, which use Total Garbage Collection during the space measurement. Several Total Space Improvements and Equivalences are shown.
Space measures for CHF* are defined, that are compatible to the space measure of LRP. An algorithm with sort-complexity is developed, that calculates the required space of independent processes that all start and end together. If a constant amount of synchronization restrictions is added and a constant number of processors is used, the runtime is polynomial, if arbitrary synchronizations are used, then the problem is NP-complete.
Abstract machines for space- and time-analyses in CHF* are developed and implementations of these are used for space and runtime analyses.
Viele Methoden wurden in dieser Arbeit vorgestellt, die sich mit dem Hauptziel der automatischen Dokumentenanalyse auf semantischer Ebene befassen. Um das Hauptziel zu erreichen, mussten wir jedoch zunächst eine solide Basis entwickeln, um das Gesamtbild zu vervollständigen. So wurden verschiedene Methoden und Werkzeuge entwickelt, die verschiedene Aspekte des NLP abdecken. Das Zusammenspiel dieser Methoden ermöglichte es, unser Ziel erfolgreich zu erreichen. Neben der automatischen Dokumentenanalyse legen wir großen Wert auf die drei Prinzipien von Effizienz, Anwendbarkeit und Sprachunabhängigkeit. Dadurch waren die entwickelten Tools für die Anwendungen bereit. Die Größe und Sprache der zu analysierenden Daten ist kein Hindernis mehr, zumindest für die im Bezug auf die von Wikipedia unterstützten Sprachen.
Einen großen Beitrag dazu leistete TextImager, das Framework, dass für die zugrunde liegende Architektur verschiedener Methoden und die gesamte Vorverarbeitung der Texte verantwortlich ist. TextImager ist als Multi-Server und Multi-Instanz-Cluster konzipiert, sodass eine verteilte Verarbeitung von Daten ermöglicht wird. Hierfür werden Cluster-Management-Dienste UIMA-AS und UIMA-DUCC verwendet. Darüber hinaus ermöglicht die Multi-Service-Architektur von TextImager die Integration beliebiger NLP-Tools und deren gemeinsame Ausführung. Zudem bietet der TextImager eine webbasierte Benutzeroberfläche, die eine Reihe von interaktiven Visualisierungen bietet, die die Ergebnisse der Textanalyse darstellen. Das Webinterface erfordert keine Programmierkenntnisse - durch einfaches Auswählen der NLP-Komponenten und der Eingabe des Textes wird die Analyse gestartet und anschließend visualisiert, so dass auch Nicht-Informatiker mit diesen Tools arbeiten können.
Zudem haben wir die Integration des statistischen Frameworks R in die Funktionalität und Architektur von TextImager demonstriert. Hier haben wir die OpenCPU-API verwendet, um R-Pakete auf unserem eigenen R-Server bereitzustellen. Dies ermöglichte die Kombination von R-Paketen mit den modernsten NLP-Komponenten des TextImager. So erhielten die Funktionen der R-Pakete extrahierte Informationen aus dem TextImager, was zu verbesserten Analysen führte.
Darüber hinaus haben wir interaktive Visualisierungen integriert, um die von R abgeleiteten Informationen zu visualisieren.
Einige der im TextImager entwickelten Visualisierungen sind besonders herausragend und haben in vielen Bereichen Anwendung gefunden. Ein Beispiel dafür ist PolyViz, ein interaktives Visualisierungssystem, das die Darstellung eines multipartiten Graphen ermöglicht. Wir haben PolyViz anhand von zwei verschiedenen Anwendungsfällen veranschaulicht.
SemioGraph, eine Visualisierungstechnik zur Darstellung multikodaler Graphen wurde auch vorgestellt. Die visuellen und interaktiven Funktionen von SemioGraph wurden mit einer Anwendung zur Visualisierung von Worteinbettungen vorgestellt. Wir haben gezeigt, dass verschiedene Modelle zu völlig unterschiedlichen Grafiken führen können. So kann Semiograph bei der Suche nach Worteinbettungen für bestimmte NLP-Aufgaben helfen.
Inspiriert von all den Textvisualisierungen im TextImager ist die Idee für text2voronoi geboren. Hier stellten wir einen neuartigen Ansatz zur bildgetriebenen Textklassifizierung vor, der auf einem Voronoi-Diagram linguistischer Merkmale basiert. Dieser Klassifikationsansatz wurde auf die automatische Patientendiagnose angewendet und wir haben gezeigt, dass wir das traditionelle Bag-Of-Words-Modell sogar übertreffen. Dieser Ansatz ermöglicht es, die zugrunde liegenden Merkmale anschließend zu analysieren und damit einen ersten Schritt zur Lösung der Black Box zu machen.
Wir haben text2voronoi auf literarische Werke angewendet und die entstandenen Visualisierungen auf einer webbasierten Oberfläche (LitViz) präsentiert. Hier ermöglichen wir den Vergleich von Voronoi-Diagrammen der verschiedenen Literaturen und damit den visuellen Vergleich der Sprachstile der zugrunde liegenden Autoren.
Mit unserer Kompetenz in der Vorverarbeitung und der Analyse von Texten sind wir unserem Ziel der semantischen Dokumentenanalyse einen Schritt näher gekommen. Als nächstes haben wir die Auflösung der Sinne auf der Wortebene untersucht. Hier stellten wir fastSense vor, ein Disambigierungsframework, das mit großen Datenmengen zurecht kommt. Um dies zu erreichen, haben wir einen Disambiguierungskorpus erstellt, der auf Wikipedias 221965 Disambiguierungsseiten basiert, wobei die sich auf 825179 Sinne beziehen. Daraus resultierten mehr als 50 Millionen Datensätze, die fast 50 GB Speicherplatz benötigten. Wir haben nicht nur gezeigt, dass fastSense eine so große Datenmenge problemlos verarbeiten kann, sondern auch, dass wir mit unseren Wettbewerbern mithalten und sie bei einigen NLP-Aufgaben sogar übertreffen können.
Jetzt, da wir den Wörtern Sinne zuordnen können, sind wir der semantischen Dokumentenanalyse einen weiteren Schritt näher gekommen. Je mehr Informationen wir aus einem Text und seinen Wörtern gewinnen können, desto genauer können wir seinen Inhalt analysieren. Wir stellten zudem einen netzwerktheoretischen Ansatz zur Modellierung der Semantik großer Textnetzwerke am Beispiel der deutschen Wikipedia vor. Zu diesem Zweck haben wir einen Algorithmus namens text2ddc entwickelt, um die thematische Struktur eines Textes zu modellieren. Dabei basiert das Modell auf einem etablierten Klassifikationsschema, nämlich der Dewey Decimal Classification. Mit diesem Modell haben wir gezeigt, wie man aus der Vogelperspektive die Hervorhebung und Verknüpfung von Themen, die sich in Millionen von Dokumenten manifestiert, darstellt. So haben wir eine Möglichkeit geschaffen, die thematische Dynamik von Dokumentnetzwerken automatisch zu visualisieren. Die Trainings- und Testdaten, die wir in diesem Kapitel hatten, bestanden jedoch hauptsächlich aus kurzen Textausschnitten. Zudem haben wir DDC Korpora erstellt, indem wir Informationen aus Wikidata, Wikipedia und der von der Deutschen Nationalbibliothek verwalteten Gemeinsamen Normdatei (GND) vereinigt haben. Auf diese Weise konnten wir nicht nur die Datenmenge erhöhen, sondern auch Datensätze für viele bisher unzugängliche Sprachen erstellen. Wir haben text2ddc so weit optimiert, dass wir einen F-score von 87.4% erzielen für die 98 Klassen der zweiten DDC-Stufe. Die Vorverarbeitung von TextImager und die Disambiguierung durch fastSense hatten einen großen Einfluss darauf. Für jedes Textstück berechnet text2ddc eine Wahrscheinlichkeitsverteilung über die DDC-Klassen berechnen
Der klassifikatorinduzierte semantische Raum von text2ddc wurde auch zur Verbesserung weiterer NLP-Methoden genutzt. Dazu gehört auch text2wiki, ein Framework für automatisches Tagging nach dem Wikipedia-Kategoriensystem. Auch hier haben wir einen klassifikatorinduzierten semantischen Raum, aber diesmal basiert er auf dem Wikipedia-Kategoriensystem. Ein großer Vorteil dieses Modells ist die Präzision und Tiefe der behandelten Themen und das sich ständig weiterentwickelnde Kategoriesystem. Damit sind auch die Kriterien eines offenen Themenmodells erfüllt. Um die Vorteile von text2wiki zu demonstrieren, haben wir anschließend die von text2wiki bereitgestellten Themenvektoren verwendet, um text2ddc zu verbessern, so dass sich beide Systeme gegenseitig verbessern können. Die Synergie zwischen den erstellten Methoden in dieser Dissertation war entscheidend für den Erfolg jeder einzelnen Methode.
Die CXCR4/CXCL12-Achse ist von entscheidender Bedeutung für die Entstehung und Aufrechterhaltung einer gesunden, reifen Hämatopoese. Erstmals beschrieben wurde der später als CXCR4 bezeichnete Rezeptor 1996 allerdings als Co-Rezeptor für den Eintritt humaner HI-Viren in Lymphozyten. Ein großes Interesse bestand daraufhin darin, sowohl natürliche Inhibitoren des G-Protein gekoppelten Rezeptors zu identifizieren, als auch synthetische herzustellen, um einen Eintritt des Virus in den menschlichen Organismus zu verhindern bzw. seine Ausbreitung zu unterbinden. Ein natürlich vorkommender CXCR4-Ligand, der 2015 von Zirafi und Kollegen erstmals beschrieben wurde, fand sich im Hämofiltrat von Dialysepatienten. Der im weiteren Verlauf als EPI-X4 bezeichnete CXCR4-Antagonist wurde als Spaltprodukt von Albumin identifiziert, welches über viele Spezies hochkonserviert ist. Diese Eigenschaft interpretieren wir als Hinweis auf eine relevante physiologische Funktion des Peptids. Da die Halbwertszeit von natürlich vorkommendem EPI-X4 beim Menschen vermutlich sehr kurz ist, sind in vivo- und darauffolgende in vitro-Analysen schwierig durchzuführen. In-vitro-Spike-Analysen von synthetischem EPI-X4 in humanem Plasma ergaben eine Halbwertszeit von nur 17 Minuten. Die geringen auftretenden Konzentrationen erschweren die Problematik zusätzlich. In dieser Arbeit sollen deshalb im Mausmodell in vivo-Analysen durchgeführt werden, um die Effekte von potentiell entstehendem EPI-X4 in verschiedenen experimentellen Ansätzen aufzudecken. Ein probates, hier verwendetes Mittel, ist die Analyse einer Knock-out (KO)-Maus. Die für die Bindung an CXCR4 entscheidende Aminosäure von EPI-X4, das am N-Terminus gelegene Leucin, wurde durch Alanin ersetzt, welches die Entstehung von EPI-X4 unterbindet und zusätzlich dessen Bindung an CXCR4 verhindert. Mit Hilfe zweier Mausmodelle können nun Analysen im EPI-X4-defizienten Modell durchgeführt werden, die im Umkehrschluss Informationen über die organismische Wirkung von EPI-X4 beinhalten. Zunächst wurde in beiden Modellen die physiologisch normale reife und unreife Hämatopoese charakterisiert. Hierbei zeigte sich kein signifikanter systematischer Einfluss von EPI-X4 auf reife Leukozyten (WBC), lediglich eine leichte Lymphozytose in der HR-Ala-Variante. Im weiteren Verlauf der homöostatischen Analyse der Hämatopoese der Ala-EPI-X4-Mäuse zeigten sich keine signifikanten Unterschiede zu wildtypischen Mäusen. Sowohl reife als auch unreife Zellen zeigten, außer in der T- und B-Zelllinie, keine zahlenmäßigen oder funktionalen Auffälligkeiten, weder im Blut, noch in der Milz oder im Knochenmark. Analysen der Zellzyklusaktivität unterschiedlicher Unreifestufen wiesen ebenfalls keine Auffälligkeiten auf. Diese Daten einer normalen, von einer C57Bl/6-Maus zu erwartenden Ergebnisse dienten als Grundlage zur Bewertung und Analyse von durchgeführten hämatopoetischen Stressmodellen. Hierfür wurden
zunächst hämatopoetische Stamm- und Vorläuferzellen (HSPC) mobilisiert. In den angewandten Mobilisierungsmodellen fanden sich lediglich unter G-CSF-Behandlung im Knochenmark eine größere Anzahl Granulozyten, was auf einen Einfluss von EPI-X4 auf HSPC schließen lässt. Um potentielle Auswirkungen von EPI-X4 im Knochenmark weiter zu untersuchen, wurde ein weiteres Stressmodell gewählt, welches ebenfalls mutmaßlich die Bedingungen zur EPI-X4-Generierung schafft: Subletale Bestrahlung der Mäuse sorgt für Schäden an allen Zellarten im Knochenmark, es wird ein steriles entzündliches Milieu kreiert. Unter diesen Umständen wurde die Regeneration von Blutzellen analysiert. Es zeigten sich keine nennenswerten Unterschiede sowohl in der akuten Phase des Schadens als auch in regelmäßigen Blutentnahmen während der Regenerierung.
Die Beschreibung von natürlich vorkommendem EPI-X4 in Vaginal- und Rektalschleimhaut zeigt seine Entstehung an Schleimhautbarrieren auf. Ala-EPI-X4-Muse werden deshalb auf deren Durchlässigkeit untersucht: LPS-Konzentrationen als Marker für eindringende pathogene Bakterien wurden im Plasma untersucht. Hierbei zeigten sich keine Unterschiede zwischen den Gruppen, eine Störung scheint hier nicht vorzuliegen. Zusätzlich wurde die Zusammensetzung des Mikrobioms im Darm untersucht, da beschrieben wurde, dass sich Mikrobiom und die Integrität der Darmschleimhaut gegenseitig beeinflussen. Im Falle der EPI-X4-defizienten Mäuse liegt zwar keine offensichtliche pathologische Veränderung vor, dennoch konnte in männlichen HR-Ala-Mäusen die Abwesenheit des Proteobakteriums Parasutterella nachgewiesen werden. Um eine mögliche Defizienz der Barrierefunktion weiter zu testen, wurden zwei Stressmodelle gewählt: Zunächst wurde den Mäusen eine akute, sterile Peritonitis zugefügt, woraufhin die Anzahl und Zusammensetzung der ins Peritoneum einströmenden Leukozyten analysiert wird. Die Reaktion auf diesen Entzündungsprozess war nicht verändert. Ähnliche Ergebnisse zeigten sich auch in einem akuten Colitis-Stressmodell.
Insgesamt konnte in dieser Arbeit mithilfe zweier KO-Mausmodelle die Rolle von EPI-X4 in der Hämatopoese und der Immunologie von Mäusen beginnend charakterisiert werden. Die homöostatische Hämatopoese scheint kaum von EPI-X4 abhängig zu sein, lediglich die Zahl der B- und T-Zellen, insbesondere der regulatorischen T-Zellen, scheint beeinflusst. Damit einhergehend konnten Veränderungen in Zytokinlevels bei inflammatorischen Ereignissen gezeigt werden. Experimente zur beeinflussten, eventuell gestörten Barrierefunktion von Ala-EPI-X4-Mäusen zeigten vielversprechende Ansätze und sollten in Zukunft weiter analysiert werden.
Natural science is only just beginning to understand the complex processes surrounding transcription. Epitranscriptional regulation is in large parts conveyed by transcription factors (TFs) and two recently discovered small RNA (smRNA) species: microRNAs (miRNAs) and transfer RNA fragments (tRFs). As opposed to the fairly well-characterised function of TFs in shaping the phenotype of the cell, the effects and mechanism of action of smRNA species is less well understood. In particular, the multi-levelled combinatorial interaction (many-to-many) of smRNAs presents new challenges to molecular biology. This dissertation contributes to the study of smRNA dynamics in mammalian cells in several ways, which are presented in three main chapters.
I) The exhaustive analysis of the many-to-many network of smRNA regulation is reliant on bioinformatic support. Here, I describe the development of an integrative database capable of fast and efficient computation of complex multi-levelled transcriptional interactions, named miRNeo. This infrastructure is then applied to two use cases. II) To elucidate smRNA dynamics of cholinergic systems and their relevance to psychiatric disease, an integrative transcriptomics analysis is performed on patient brain sample data, single-cell sequencing data, and two closely related in vitro human cholinergic cellular models reflecting male and female phenotypes. III) The dynamics between small and large RNA transcripts in the blood of stroke victims are analysed via a combination of sequencing, analysis of sorted blood cell populations, and bioinformatic methods based on the miRNeo infrastructure. Particularly, importance and practicality of smRNA:TF:gene feedforward loops are assessed.
In both analytic scenarios, I identify the most pertinent regulators of disease-relevant processes and biological pathways implicated in either pathogenesis or responses to the disease. While the examples described in chapters three and four of this dissertation are disease-specific applications of miRNeo, the database and methods described have been developed to be applicable to the whole genome and all known smRNAs.
The subject matter of this article is Axel Honneth’s theory of recognition as it has been exposed in his more recent book, Das Recht der Freiheit. Throughout the paper his attempts to describe injustices within modern capitalist societies using the notions of pathologies and anomie will be analyzed and criticized, especially from the viewpoint of their inability to deal with processes and contexts of disrecognition (Aberkennung). With help of this category, Honneth’s diagnosis regarding the moral progress in modern societies, as well as his notion of second order disorders, as injustices will be confronted and, hopefully, complemented.
While liberal, redistributive views seek to correct and compensate for past injustices, by resorting to compensatory, procedural arguments for corrective justice, the recognition-based, communitarian arguments tend to promote by means of social movements and struggles for recognition a society free from prejudice and disrespect. In developing democratic societies such as Brazil, Axel Honneth’s contribution to the ongoing debates on Affirmative Action has been evoked, confirming that the dialectics of recognition does not merely seek a theoretical solution to the structural and economic inequalities that constitute some of their worst social pathologies, but allows for practices of self-respect and subjectivation that defy all technologies of social control, as pointed out in Foucault’s critique of power. The phenomenological deficit of critical theory consists thus in recasting the critique of power with a view to unveiling lifeworldly practices that resist systemic domination.
This paper describes the revision of the Vietnamese version of the Multilingual Assessment Instrument for Narratives (LITMUS-MAIN). We first introduce the Vietnamese language and Vietnamese-speaking populations after which we describe the translation and adaptation process of the Vietnamese MAIN and present results from monolingual and bilingual children.
The Multilingual Assessment Instrument for Narratives (MAIN), an assessment tool in the Language Impairment Testing in Multilingual Settings (LITMUS) battery, aims to improve the assessment of bilingual children. This paper describes the process of adapting MAIN to Urdu. Given the lack of language assessment tools for Urdu-speaking children, the Urdu MAIN is an important new instrument that is made widely and freely accessible to researchers and practitioners, allowing them to examine the narrative abilities of children acquiring Urdu as a first, heritage, second, or additional language.
This paper presents a short overview of Turkey and the Turkish language, and then outlines the process of adapting the Multilingual Assessment Instrument for Narratives (MAIN) to Turkish and how the Turkish MAIN has been used with monolingual and bilingual children. The grammatical features of Turkish, the critical points in the adaptation process of MAIN to Turkish and our experiences of extensive piloting of the Turkish MAIN with typically developing monolingual children are described.
Torwali, a Dardic language of the Indo-Aryan family spoken in the District Swat in Pakistan, is an endangered language that lacks a literary tradition. This paper gives a background on the Torwali language and people, and describes the development of an orthography for Torwali and the establishment of Torwali-medium schools by the local organization Idara Baraye Taleem-o-Taraqi ‘institute for education and development’ (IBT). Finally, the process of adapting the Multilingual Assessment Instruments for Narratives (MAIN) to Torwali is outlined.
This paper briefly presents the current situation of bilingualism in the Philippines, specifically that of Tagalog-English bilingualism. More importantly, it describes the process of adapting the Multilingual Assessment Instrument for Narratives (LITMUS-MAIN) to Tagalog, the basis of Filipino, which is the country’s national language. Finally, the results of a pilot study conducted on Tagalog-English bilingual children and adults (N=27) are presented. The results showed that Story Structure is similar across the two languages and that it develops significantly with age.
In this paper, we present some features of the European Spanish adaptation of the Multilingual Assessment Instrument for Narratives (LITMUS-MAIN), most of them related to specificities of the Spanish grammar as compared to English, the source language of the original MAIN (Gagarina et al., 2012). These two languages differ in e.g. 1) the use of 3rd grammatical person to address the hearer; 2) the ways of maintaining nominal cohesion: English (non-pro drop) vs. Spanish (pro-drop); 3) the verbal paradigm with regard to morphological tense and aspect morphology. Finally, preliminary results for micro- and macrostructure measures in the narratives of children with Spanish as L1 and L2 confirm their consistency across MAIN stories and procedures.
Using MAIN in South Africa
(2020)
South Africa is a country marked by cultural and linguistic diversity with 11 official languages. The majority of school children do not receive their formal schooling in their home language. There is a need for language assessment tools in education and rehabilitation contexts to distinguish between children with language learning problems and/or SLI, and language delay as a result of limited exposure to the language of learning. The Multilingual Assessment Instrument for Narratives (LITMUS-MAIN) provides clinicians and researchers with an appropriate and culturally relevant tool to assess bilingual children in both languages. So far MAIN has been widely used in Afrikaans-English bilingual children. However, translating and adapting MAIN to our other nine official languages to achieve functional and cultural equivalence is more challenging.
The adaptation of the Multilingual Assessment Instrument for Narratives (LITMUS-MAIN) for use with Slovak speaking children is a vital step in the process of creating a transparent evaluation of children’s narrative abilities. Since its first translation and adaptation in 2012, new pilot data from different groups of children has been collected in Slovakia. This paper describes the process of adapting the instrument to fit the Slovak language and reports on analyses of narrative production in monolingual (103 Slovak-speaking children) and bilingual (37 Slovak-English speaking) pre-school children. Within a pilot study, the story elicitation method was also compared (telling vs. retelling) within a small sample of 10 monolingual Slovak-speaking children. All results show transparent and detailed possibilities in terms of finding a meaningful evaluation that can evaluate a child’s complex narrative abilities.
This paper provides the background to the process of translation and piloting of the Serbian version of the Multilingual Assessment Instrument for Narratives (LITMUS-MAIN), Multilingvalni Test za Procenu Narativa (MTPN). Our review of the sparse research literature on Serbian children’s narrative abilities reveals a need for a well-designed narrative instrument, which will enable researchers and practitioners to assess the production and comprehension of narratives in children of a wide age range, typically and atypically developing, monolingual and bilingual, crucially allowing for cross-linguistic comparisons. We encountered two kinds of challenges during the process of translation and adaptation of the instrument from English into Serbian. The first concerned the lack of established Serbian technical terminology needed to describe test administration to the future users of the test: researchers and practitioners working in different disciplines such as linguistics, psychology, Speech and Language Therapy. The second challenge concerned the translation of linguistic structures required to produce a successful rendition of the narrative: in contrast to English, but in line with other Slavic languages, Serbian relies heavily on verbs marked for perfective aspect in story-telling. Our discussion of preliminary data from four Serbian monolingual children, aged 5;5-10, demonstrates that MTPN is a successful tool in assessing narrative abilities in children acquiring Serbian.
A translation process is often seen as only a simple code exchange, but, in fact, it always requires an adaptation of terms, expressions, and structures, which is not exactly straightforward. This paper describes the process of translating and adapting the Multilingual Assessment Instrument for Narratives (LITMUS-MAIN) to Brazilian Portuguese. A brief description of the project, concerning both historic and linguistic aspects, was done in order to emphasize the cultural and linguistic challenges faced during the process.
This paper describes in detail the development of the Polish version of the Multilingual Assessment Instrument for Narratives (LITMUS-MAIN). We first describe its two earlier versions, the unpublished version and the published version, developed in 2012, as well as the revised version. We also justify the differences between the unpublished Polish version developed in 2012 and the original MAIN. Then we summarize the results from studies that used the unpublished version of the Polish MAIN. We end with outlining a study that could be conducted to compare the two slightly different procedures in order to examine whether the results obtained with MAIN are resistant to changes in the procedure details.
This paper describes the experience of using the Norwegian and Russian versions of LITMUS-MAIN to elicit narrative data from bilingual Norwegian-Russian children as well as from Norwegian- and Russian-speaking monolinguals (Rodina 2017, 2018). The paper reports on the slight adaptations to the standardized design, procedure and analysis that were done to make the tasks more suitable for this specific population. It highlights the advantages, challenges, and potential associated with the task against a backdrop of the research conducted with Norwegian-Russian bilinguals in Norway.
This paper introduces the Mandarin version of the Multilingual Assessment Instrument for Narratives (LITMUS-MAIN) and describes the adaptation process. The Mandarin MAIN not only extends the empirical coverage of MAIN by including one of the most widely spoken languages in the world, but also offers an important tool to assess the narrative abilities of monolingual and bi-/ multi- lingual children acquiring Mandarin as a first, heritage, second, or additional language across the globe.
This paper describes the addition of Luxembourgish to the language versions of MAIN, the adaption process and the use of MAIN in Luxembourg. A short description of Luxembourg’s multilingual society and trilingual school system as well as an overview of selected morphosyntactic and syntactic features of Luxembourgish introduce the Luxembourgish version of MAIN.
This paper introduces the Kam version of the Multilingual Assessment Instrument for Narratives (LITMUS-MAIN). Kam is a minority language in southern China which belongs to the Kam-Tai language family and is spoken by the Kam ethnic minority people. Adding Kam to MAIN not only enriches the typological diversity of MAIN but also allows researchers to study children’s narrative development in a sociocultural context vastly distinctly different from the frequently examined WEIRD (Western, Educated, Industrialized, Rich, and Democratic) societies. Moreover, many Kam-speaking children are bilingual ethnic minority children who are “left-behind” children living in Mainland China, growing up in a unique socio-communicative environment
This paper presents the Italian version of the Multilingual Assessment tool for Narratives (MAIN), describes how it was developed and reports on some recent uses of MAIN within the Italian context. The Italian MAIN has been used in different research projects and for clinical purposes; results have been presented at conferences and in peer reviewed papers. The results indicate that MAIN is an appropriate assessment tool for evaluating children’s narrative competence, in production and comprehension from preschool age (5 years) to school age (8 years) in typical language development, bilingual development and language delay/disorders.
Irish (Gaeilge) is the first official language of the Republic of Ireland. It is a fast-changing, endangered language. Almost universal bilingualism (i.e. almost all Irish speakers also speak English), frequent code-switching to English, and loan words are features of the sociolinguistic context in which the language is spoken. This paper describes the adaptation of the Language Impairment Testing in Multilingual Settings - Multilingual Assessment Instrument for Narratives (LITMUS-MAIN, Gagarina et al., 2019) to Irish. Data was collected using the retell mode (Cat story) and the comprehension questions. Eighteen children participated ranging in age from 5;3 to 8;7 (six female and 12 male). Results suggest that story structure is not sensitive to exposure to Irish at home and indicate that MAIN Gaeilge (Irish) is a promising tool for assessing language in Irish-speaking children from a range of Irish language backgrounds.
Immigration in Iceland has a short history and so does the Icelandic language as an L2. This paper gives a brief introductory overview of this history and of some characteristics of the Icelandic language that constitute a challenge for L2 learners but also make it an interesting testing ground for cross-linguistic comparisons of L1 and L2 language acquisition. It then describes the adaptation process of the Multilingual Assessment Instrument for Narratives (LITMUS-MAIN) to Icelandic. The Icelandic MAIN is expected to fill a gap in available assessment tools for multilingual Icelandic speaking children.
The Multilingual Assessment Instrument for Narratives (LITMUS-MAIN) was developed to assess the narrative abilities of bi- and multilingual children in the various languages that they speak. This paper presents the details of the adaptation of MAIN to three Indian languages, Kannada, Hindi and Malayalam. We describe some typological features of these languages and discuss the challenges faced during the process of adaptation. Finally, we give an overview of results for narrative comprehension and production from Kannada-English and Hindi-English bilinguals aged 7 to 9.
This paper presents an overview of the adaptation of the Multilingual Assessment Instrument for Narratives in Greek, focusing on its use in Greek academic and diagnostic settings. A summary of the properties of the Greek language and the concomitant challenges these language-specific properties posed to MAIN adaptation are presented along with a summary of published studies with monolingual Greek-speaking children and bilingual children with Greek as L2, with and without Developmental Language Disorder.
This paper presents the adaptation of MAIN to Gondi (Dantewada), Halbi and Hindi for Gondi-Hindi and Halbi-Hindi bilinguals. The Gondi and Halbi communities and the context in which Gondi-Hindi and Halbi-Hindi bilingual children are growing up are described, and the adaptation process is outlined together with its theoretical underpinnings. Finally, results from a study of 54 Halbi-Hindi bilinguals from Grade 3 (Mean age = 8.5 years), Grade 5 (Mean age = 10.9 years) and Grade 7 (Mean age = 12.9 years) are presented. The results showed that, for the macrostructure of Grade 3 and Grade 5, L1 retelling was significantly better than L2 retelling, though this pattern was not found in Grade 7 where the performance was at the same level across languages for retelling. Narrative macrostructure was consistently higher in tellings than in the retellings regardless of languages and grades.
This paper describes the rationale for the adaptation of the Multilingual Assessment Instrument for Narratives (LITMUS-MAIN) (Gagarina et al., 2012, 2015, 2019) to Scottish Gaelic (Gaelic) and presents some preliminary results from the macrostructure measures. Gaelic is a heritage minority language in Scotland being revitalised through immersion education, which spans across all levels of compulsory education (preschool, primary and secondary level). MAIN was adapted to Gaelic for two reasons: (i) to gauge the language abilities of children attending Gaelic immersion schools using an ecologically valid test, and (ii) to help identify areas of language impairment in children with Developmental Language Disorders within a broader battery of language tasks. Preliminary results from the macrostructure component indicate a wider range of Gaelic language abilities in six- to eight-year-old typically developing children in Gaelic-medium education. These results set the stage for future use of the tool within this context.
This paper describes the current state of affairs concerning the West Frisian adaptation of the Multilingual Assessment Instrument for Narratives (MAIN). We provide a short description of the West Frisian language, the process of adapting MAIN into West Frisian and the results of recent research using this adaptation.
This paper describes Estonian version of the Multilingual Assessment Instrument for Narratives (LITMUS-MAIN) to Estonian. A short description of Estonian, some challenges in the adapting MAIN to Estonian, the first experiences of using the Estonian MAIN and a summary of the first results are presented.
This contribution provides an overview of the current state of affairs with respect to the Dutch version of the Multilingual Assessment Instrument for Narratives (MAIN). We describe properties of the Dutch MAIN, the creation of the Dutch MAIN, and the results of recent research with this new instrument to measure narrative competence.
This paper describes the process of adapting the Multilingual Assessment Instrument for Narratives (LITMUS-MAIN) to Danish and the use of MAIN in a Danish context. First, there is a brief description of the Danish language followed by details of the process of translating and adapting the MAIN manual to Danish. Finally, we briefly describe some of the research contexts in which the current and previous MAIN materials have been piloted and applied.
This paper presents the Croatian version of the Multilingual Assessment tool for Narratives (MAIN), outlines its development and describes the research that has used it to assess narrative skills in monolingual and bilingual speakers. The Croatian version of MAIN has so far been used in three research projects and results have been presented in five peer-reviewed articles (published or in press) covering a total of 175 children in the age range from 5;0 to 9;0 (20 with developmental language disorder) and 60 adults, age range from 22 to 76. The accumulated results indicate that MAIN can differentiate narrative skills of speakers in distinct age groups and can distinguish children with language disorders form children with typical language development.
The adaptation of the Multilingual Assessment Instrument for Narratives (LITMUS-MAIN; Gagarina, et al., 2019) to Catalan contributes to advancing our knowledge of the development of children’s narrative skills in a diversity of languages using the same protocol, making it possible to evaluate narratives also in Catalan-speakers. The adaptation of MAIN will be very useful in Catalonia, because it is a region where two official languages (Catalan and Spanish) coexist, Catalan being the language of schooling, so that most of the population is bilingual. However, currently there is no instrument for assessing narrative skills that allows for parallel assessment of Catalan in bilingual children. For these reasons, this adaptation will be of great value to promote the study of narratives in the bilingual population considering Catalan within the possible language combinations. The present paper describes the process of adapting MAIN to Catalan and reports results from the first pilot study using the Catalan MAIN.
This paper gives an introduction to the Cantonese adaptation of Multilingual Assessment Instrument for Narratives (MAIN), which is part of the Language Impairment Testing in Multilingual Settings (LITMUS) battery. We here discuss the motivation for adapting this assessment instrument into Cantonese, the adaptation process itself and potential contexts for use of the Cantonese MAIN.
Bulgarian belongs to the South Slavic language group but exhibits specific linguistic features shared with the non-Slavic languages of the Balkan Sprachbund. In this paper, we discuss linguistic and cultural aspects relevant for the Bulgarian adaptation of the revised English version of The Multilingual Assessment Instrument for Narratives (LITMUS-MAIN). We address typological properties of the verbal system pertaining to a differentiated aspectual system and to a paradigm of verbal forms for narratives grammaticalized as renarrative mood in Bulgarian. Further, we consider lexical, derivational and discourse cohesive means in contrast to the English markers of involvement and perspective taking in the MAIN stories.
Adapting MAIN to Arabic
(2020)
Preface: New language versions of MAIN: Multilingual Assessment Instrument for Narratives - revised
(2020)
The Multilingual Assessment Instrument for Narratives (MAIN) is a theoretically grounded toolkit that employs parallel pictorial stimuli to explore and assess narrative skills in children in many different languages. It is part of the LITMUS (Language Impairment Testing in Multilingual Settings) battery of tests that were developed in connection with the COST Action IS0804 Language Impairment in a Multilingual Society: Linguistic Patterns and the Road to Assessment (2009−2013). MAIN has been designed to assess both narrative production and comprehension in children who acquire one or more languages from birth or from early age. Its design allows for the comparable assessment of narrative skills in several languages in the same child and in different elicitation modes: Telling, Retelling and Model Story. MAIN contains four parallel stories, each with a carefully designed six-picture sequence based on a theoretical model of multidimensional story organization. The stories are controlled for cognitive and linguistic complexity, parallelism in macrostructure and microstructure, as well as for cultural appropriateness and robustness. As a tool MAIN had been used to compare children’s narrative skills across languages, and also to help differentiate between children with and without developmental language disorders, both monolinguals and bilinguals.
This volume consists of two parts. The main content of Part I consists of 33 papers describing the process of adapting and translating MAIN to a large number of languages from different parts of the world. Part II contains materials for use for about 80 languages, including pictorial stimuli, which are accessible after registration.
MAIN was first published in 2012/2013 (ZASPiL 56). Several years of theory development and material construction preceded this launch. In 2019 (ZASPiL 63), the revised English version (revised on the basis of over 2,500 transcribed MAIN narratives as well as ca 24,000 responses to MAIN comprehension questions, collected from around 700 monolingual and bilingual children in Germany, Russia and Sweden between 2013-2019) was published together with revised versions in German, Russian, Swedish, and Turkish for the bilingual Turkish-Swedish population in Sweden. The present 2020 (ZASPiL 64) volume contains new and revised language versions of MAIN.
Sea pens (Cnidaria: Anthozoa: Pennatulacea) constitute a distinctive group of colonial marine invertebrates. They inhabit the world`s oceans, from shallow to deep waters. Studies about this group in Argentina are scarce, and no species have been described in the area in over a decade. Based on samples collected in Mar del Plata Submarine Canyon at about 3000 m deep we describe a new species of sea pen, Umbellula pomona Risaro, Williams & Lauretta sp. nov. This is a spiculate Umbellula that differs from other species of Umbellula with sclerites, by the number, development and distribution of the autozooids in its terminal cluster, as well as the shape of its axis. Molecular data also distinguishes it from other known species. Of the forty-three described species approximately ten are considered valid for the genus Umbellula, four of them are registered for the South Atlantic Ocean and only three are described for the Antarctic region. Since sampling efforts in this area have been scarce, the number of species of sea pens from the region is likely to increase substantially in the coming years.
The p38α mitogen-activated protein kinase (MAPK) is activated through stress stimuli such as heat shock or hypoxia. In the nucleus, p38α modulates the activity of other kinases and transcription factors, a process that regulates the expression of specific target genes, most importantly pro-inflammatory cytokines. Dysregulation of p38α therefore plays a major role in the development of inflammatory diseases such as rheumatoid arthritis. Despite many years of intensive research, no p38 small-molecule inhibitors have been approved yet. Several inhibitor design strategies have been reported, leading to >100-fold selective compounds for α/β over the γ and δ isoforms. Achieving such a selectivity among the two structurally most related α and β isoforms, however, remains a challenging task. Targeting an inactive DFG-out conformation offers another strategy for the development of potent kinase inhibitors (type-II), exemplified by the BCR/ABL-inhibitor Imatinib. Achieving selectivity with type-II binders is challenging, because many kinases can adopt an inactive DFG-out conformation. This is exemplified by the p38 type-II inhibitor BIRB-796, which exhibits picomolar on-target affinity but only a poor kinome-wide selectivity. A potent and selective type-II chemical probe for p38α/β was still lacking at the start of this thesis.
The promising hit VPC-00628, was chosen for a combinatorial synthetic approach to develop a type-II chemical probe. The studies covered the optimization of the hinge-binding head group, the hydrophobic region I and the DFG-out deep pocket of the lead compound VPC-00628. Selectivity for the p38α and p38β isoforms was monitored during the optimization process, which identified several inhibitors with favorable isoform selectivity, providing valuable insights into the potential of isoform-selective inhibitor design for p38. A potent and highly selective p38 MAPK probe (SR-318) was discovered, which showed IC50 values in the low nanomolar range in HEK293T cells. An unusual P-loop conformation induced upon binding of SR-318 to p38α contributed most likely to the impressive selectivity profile within the kinome that surpassed both the parent compound and BIRB-796. A negative control compound, SR-321, was developed, to distinguish between on-target effects and non-specific effects due to cross-reactivity with other cellular proteins. Studies of the metabolic stability in human liver microsomes revealed a high stability of the compounds, with only a small amount of metabolites formed over several hours. Compound SR-318 also exhibited a good in vitro efficacy, quantitatively reducing the LPS-stimulated TNF-α release in whole blood. Taken together, SR-318 is a highly potent and selective type-II p38α/β chemical probe, which will help to gain a better understanding of the catalytic and non-catalytic functions of these key signaling kinases in physiology and pathology.
The next studies focused on the exploration of the highly dynamic allosteric back pocket of p38 MAPK, and allosteric BIRB-796 derived compounds for targeting the αC- and DFG-out pockets were synthesized. Kinase activities of allosteric pyrazole-urea fragments were analyzed against a comprehensive set of 47 diverse kinases by differential scanning fluorimetry (DSF), revealing that BIRB-796 off-targets remain a problem when targeting this back-pocket binding motif. Revisiting the recently published compound MCP-081, which combines the allosteric part of BIRB-796 with the active-site directed part of VPC-00628, showed that it displays a clean selectivity profile in our kinase panel. Because the potency of MCP-081 was slightly reduced compared with VPC-00628 and the allosteric tert-butyl pyrazole moiety seemed suboptimal, a set of VPC-00628 derivatives for targeting the αC-out pocket region was synthesized. Through structure-guided extension of the terminal amide of VPC-00628 toward this allosteric site, the potent and selective compound SR-43 was developed, which showed excellent cellular activity on p38 MAPK in NanoBRETTM assays (IC50 [p38α/β] = 14.0 ± 0.1/ 16.8 ± 0.1 nM). SR-43 showed a dose-dependent inhibition of activating phosphorylation of p38 in HCT-15 cells as well as inhibition of phosphorylation of p38 downstream substrates MK2 and Hsp27. In addition, SR-43 induced an anti-inflammatory response by blocking TNF-α release in whole blood and displayed a high metabolic stability. Selectivity profiling of SR-43 revealed a narrow selectivity for additional targets such as the discoidin domain receptor kinases (DDR1/2). DDR kinases play a central role in fibrotic disorders, such as renal and pulmonale fibrosis, atherosclerosis and different forms of cancer. Since selective and potent inhibitors for these important therapeutic targets are largely lacking and the existing inhibitors are of low scaffold diversity, the next study focused on the optimization of SR-43 toward DDR1/2 kinase inhibition. The synthetic work covered the optimization of the hinge-binding head group and the allosteric part of SR-43 toward DDR1/2 kinase inhibition. These studies provided novel insights into the P-loop folding process of p38 MAPK and how targeting of non-conserved amino acids affects inhibitor selectivity. Importantly, they led to the development of a selective dual DDR/p38 inhibitor probe, SR-302, with picomolar affinity for DDR2. SR-302 was efficient in vitro and showed a destabilizing effect on the surface adhesion protein E-cadherin in epithelial cells. In summary, SR-302 and its negative control SR-301 provide a valuable tool set for studying the phenotypic effects of DDR1/2 signaling, e.g., in cancer cell lines.
Dichromatobolus, a new genus of spirobolidan millipedes from Madagascar (Spirobolida, Pachybolidae)
(2020)
A new genus, Dichromatobolus gen. nov., belonging to the genus-rich mainly southern hemisphere family Pachybolidae of the order Spirobolida, is described based on D. elephantulus gen. et sp. nov., illustrated with color pictures, line drawings, and scanning electron micrographs. The species is recorded from the spiny bush of southwestern Madagascar. Dichromatobolus elephantulus gen. et sp. nov. shows an unusual color pattern, sexual dichromatism with males being red with black legs and females being grey. Males seem to be more surface active, as mainly males were collected with pitfall traps. Females mainly come from the pet trade. The body of this species is short and very wide, being only 8 times longer than wide in the males. Live observations show the species is a very slow mover, digging in loose soil almost as fast as walking on the surface. The posterior gonopods of Dichromatobolus gen. nov. are unusually simple and well-rounded, displaying some similarities to the genera Corallobolus Wesener, 2009 and Granitobolus Wesener, 2009, from which the new genus differs in numerous other characters, e.g., size, anterior gonopods and habitus. Despite several attempts with fresh tissue samples and different primers, molecular barcoding did not work for Dichromatobolus gen. nov. Any relationships to the other 15 genera of Pachybolidae indigenous to Madagascar remain unknown.
Background: Zolpidem is a non-benzodiazepine hypnotic agent which has been shown to be effective in inducing and maintaining sleep in adults and is one of the most frequently prescribed hypnotics in the world. For drugs that are used to treat sleeping disorders, the time to reach the maximum concentration (Tmax) of the drug in plasma is important to achieving a fast onset of action and this must be maintained when switching from one product to another.
Objectives: The main objective of the present work was to create a PBPK/PD model for zolpidem and establish a clinically relevant “safe space” for dissolution of zolpidem from the commercial immediate release (IR) formulation. A second objective was to analyze literature pharmacokinetic data to verify the negative food effect ascribed to zolpidem and consider its ramifications in terms of the “safe space” for dissolution.
Methods: Using dissolution, pharmacokinetic and pharmacodynamic data, an integrated PBPK/PD model for immediate release zolpidem tablets was constructed in Simcyp®. This model was used to identify the clinically relevant dissolution specifications necessary to ensure efficacy.
Results: According to the simulations, as long as 85% of the drug is released in 45 minutes or less, the impact on the PK and PD profiles of zolpidem would be minimal. According to the FDA, the drug has to dissolve from the test and reference products at a similar rate and to an extent of 85% in not more than 30 minutes to pass bioequivalence via the BCS-biowaiver test. Thus, the BCS-biowaiver specifications are somewhat more stringent than the “safe space” based on the PBPK/PD model. Published data from fasted and fed state pharmacokinetic studies suggest but do not prove a negative food effect of zolpidem.
Conclusions: A PBPK/PD model indicates that current BCS biowaiver criteria are more restrictive for immediate release zolpidem tablets than they need to be. In view of the close relationship between PK and PD, it remains advisable to avoid taking zolpidem tablets with or immediately after a meal, as indicated by the Stilnox® labeling.
In this study, we examine 500 specimens of Anaplecta collected from China, of which 26 samples were used for COI sequencing. We confirm eight new species, i.e., Anaplecta corneola Deng & Che sp. nov., Anaplecta staminiformis Deng & Che sp. nov., Anaplecta arcuata Deng & Che sp. nov., Anaplecta strigata Deng & Che sp. nov., Anaplecta furcata Deng & Che sp. nov., Anaplecta cruciata Deng & Che sp. nov., Anaplecta nigra Deng & Che sp. nov. and Anaplecta bicolor Deng & Che sp. nov. based on morphological and molecular data using ABGD and GMYC analyses. The results of ABGD and GMYC were basically consistent with the morphospecies of Anaplecta. The intraspecific and interspecific genetic distances of Anaplecta ranged from 0 to 6.6% and 16.8% to 31.8%, respectively. We found the male genitalia of Anaplecta to exhibit intraspecific variation, especially in the phallomeres.
Background: While systemic inflammation is recognized as playing a central role in the pathogenesis of organ failures in patients with liver cirrhosis, less is known about its relevance in the development of classical hepatic decompensation. Aim: To characterize the relationship between systemic inflammation, hemodynamics, and anemia with decompensation of liver cirrhosis. Methods: This is a post-hoc analysis of a cohort study of outpatients with advanced liver fibrosis or cirrhosis. Results: Analysis included 338 patients of whom 51 patients (15%) were hospitalized due to decompensation of liver cirrhosis during a median follow-up time of six months. In univariate analysis, active alcoholism (p = 0.002), model of end-stage liver disease (MELD) score (p = 0.00002), serum IL-6 concentration (p = 0.006), heart rate (p = 0.03), low arterial blood pressure (p < 0.05), maximal portal venous flow (p = 0.008), and low hemoglobin concentration (p < 0.00001) were associated with hospitalization during follow-up. Multivariate analysis revealed an independent association of low hemoglobin (OR = 0.62, 95% CI = 0.51–0.78, p = 0.001) and serum IL-6 concentration (OR = 1.02, 95% CI = 1.01–1.04, p = 0.03)—but not of hemodynamic parameters—with hepatic decompensation. An inverse correlation between hemoglobin concentration and portal venous flow (R = −0.362, p < 0.0001) was detected for the non-hospitalized patients. Accuracy of baseline hemoglobin levels for predicting hospitalization (AUC = 0.84, p < 0.000001) was high. Conclusion: Anemia and systemic inflammation, rather than arterial circulatory dysfunction, are strong and independent predictors of hepatic decompensation in outpatients with liver cirrhosis.
Background: Sepsis frequently occurs after major trauma and is closely associated with dysregulations in the inflammatory/complement and coagulation system. Thrombin-activatable fibrinolysis inhibitor (TAFI) plays a dual role as an anti-fibrinolytic and anti-inflammatory factor by downregulating complement anaphylatoxin C5a. The purpose of this study was to investigate the association between TAFI and C5a levels and the development of post-traumatic sepsis. Furthermore, the predictive potential of both TAFI and C5a to indicate sepsis occurrence in polytraumatized patients was assessed. Methods: Upon admission to the emergency department (ED) and daily for the subsequent ten days, circulating levels of TAFI and C5a were determined in 48 severely injured trauma patients (injury severity score (ISS) ≥ 16). Frequency matching according to the ISS in septic vs. non-septic patients was performed. Trauma and physiologic characteristics, as well as outcomes, were assessed. Statistical correlation analyses and cut-off values for predicting sepsis were calculated. Results: Fourteen patients developed sepsis, while 34 patients did not show any signs of sepsis (no sepsis). Overall injury severity, as well as demographic parameters, were comparable between both groups (ISS: 25.78 ± 2.36 no sepsis vs. 23.46 ± 2.79 sepsis). Septic patients had significantly increased C5a levels (21.62 ± 3.14 vs. 13.40 ± 1.29 ng/mL; p < 0.05) and reduced TAFI levels upon admission to the ED (40,951 ± 5637 vs. 61,865 ± 4370 ng/mL; p < 0.05) compared to the no sepsis group. Negative correlations between TAFI and C5a (p = 0.0104) and TAFI and lactate (p = 0.0423) and positive correlations between C5a and lactate (p = 0.0173), as well as C5a and the respiratory rate (p = 0.0266), were found. In addition, correlation analyses of both TAFI and C5a with the sequential (sepsis-related) organ failure assessment (SOFA) score have confirmed their potential as early sepsis biomarkers. Cut-off values for predicting sepsis were 54,857 ng/mL for TAFI with an area under the curve (AUC) of 0.7550 (p = 0.032) and 17 ng/mL for C5a with an AUC of 0.7286 (p = 0.034). Conclusion: The development of sepsis is associated with early decreased TAFI and increased C5a levels after major trauma. Both elevated C5a and decreased TAFI may serve as promising predictive factors for the development of sepsis after polytrauma.
Low-to-moderate quality meta-analytic evidence shows that motor control stabilisation exercise (MCE) is an effective treatment of non-specific low back pain. A possible approach to overcome the weaknesses of traditional meta-analyses would be that of a prospective meta-analyses. The aim of the present analysis was to generate high-quality evidence to support the view that motor control stabilisation exercises (MCE) lead to a reduction in pain intensity and disability in non-specific low back pain patients when compared to a control group. In this prospective meta-analysis and sensitivity multilevel meta-regression within the MiSpEx-Network, 18 randomized controlled study arms were included. Participants with non-specific low back pain were allocated to an intervention (individualized MCE, 12 weeks) or a control group (no additive exercise intervention). From each study site/arm, outcomes at baseline, 3 weeks, 12 weeks, and 6 months were pooled. The outcomes were current pain (NRS or VAS, 11 points scale), characteristic pain intensity, and subjective disability. A random effects meta-analysis model for continuous outcomes to display standardized mean differences between intervention and control was performed, followed by sensitivity multilevel meta-regressions. Overall, 2391 patients were randomized; 1976 (3 weeks, short-term), 1740 (12 weeks, intermediate), and 1560 (6 months, sustainability) participants were included in the meta-analyses. In the short-term, intermediate and sustainability, moderate-to-high quality evidence indicated that MCE has a larger effect on current pain (SMD = −0.15, −0.15, −0.19), pain intensity (SMD = −0.19, −0.26, −0.26) and disability (SMD = −0.15, −0.27, −0.25) compared with no exercise intervention. Low-quality evidence suggested that those patients with comparably intermediate current pain and older patients may profit the most from MCE. Motor control stabilisation exercise is an effective treatment for non-specific low back pain. Sub-clinical intermediate pain and middle-aged patients may profit the most from this intervention.
In the course of a growing start-up market and strongly increasing investment volume, investors try to predict the success of a business as precisely as possible in advance. However, when assessing the personality of the founder or founding team, they still rely far too often on their gut feeling, thereby reducing the quality of their decisions. Our study therefore aimed at investigating whether there are any relationships between the founders' personality traits and their performance and thus justifying the need for more targeted and optimized diagnostics in the field of founder personality. With a total of 141 founders, clear correlations between personality traits (conscientiousness, emotional stability) and performance could be demonstrated in the present study. In addition, it became evident that perceived stress is also related to the founders’ personality (emotional stability negative, conscientiousness positive) and in turn has a negative effect on performance. Our findings contribute to raising awareness of the importance of personality as a predictor of founders' performance, improving decision-making, and, in the long run, replacing gut feeling as an inappropriate assessment criterion of investors.
Background: More than 170 species of tabanids are known in Europe, with many occurring only in limited areas or having become very rare in the last decades. They continue to spread various diseases in animals and are responsible for livestock losses in developing countries. The current monitoring and recording of horseflies is mainly conducted throughout central Europe, with varying degrees of frequency depending on the country. To the detriment of tabanid research, little cooperation exists between western European and Eurasian countries.
Methods: For these reasons, we have compiled available sources in order to generate as complete a dataset as possible of six horsefly species common in Europe. We chose Haematopota pluvialis, Chrysops relictus, C. caecutiens, Tabanus bromius, T. bovinus and T. sudeticus as ubiquitous and abundant species within Europe. The aim of this study is to estimate the distribution, land cover usage and niches of these species. We used a surface-range envelope (SRE) model in accordance with our hypothesis of an underestimated distribution based on Eurocentric monitoring regimes.
Results: Our results show that all six species have a wide range in Eurasia, have a broad climatic niche and can therefore be considered as widespread generalists. Areas with modelled habitat suitability cover the observed distribution and go far beyond these. This supports our assumption that the current state of tabanid monitoring and the recorded distribution significantly underestimates the actual distribution. Our results show that the species can withstand extreme weather and climatic conditions and can be found in areas with only a few frost-free months per year. Additionally, our results reveal that species prefer certain land-cover environments and avoid other land-cover types.
Conclusions: The SRE model is an effective tool to calculate the distribution of species that are well monitored in some areas but poorly in others. Our results support the hypothesis that the available distribution data underestimate the actual distribution of the surveyed species.
Reduced external knee adduction moments in the second half of stance after total hip replacement have been reported in hip osteoarthritis patients. This reduction is thought to shift the load from the medial to the lateral knee compartment and as such increase the risk for knee osteoarthritis. The knee adduction moment is a surrogate for the load distribution between the medial and lateral compartments of the knee and not a valid measure for the tibiofemoral contact forces which are the result of externally applied forces and muscle forces. The purpose of this study was to investigate whether the distribution of the tibiofemoral contact forces over the knee compartments in unilateral hip osteoarthritis patients 1 year after receiving a primary total hip replacement differs from healthy controls. Musculoskeletal modeling on gait was performed in OpenSim using the detailed knee model of Lerner et al. (2015) for 19 patients as well as for 15 healthy controls of similar age. Knee adduction moments were calculated by the inverse dynamics analysis, medial and lateral tibiofemoral contact forces with the joint reaction force analysis. Moments and contact forces of patients and controls were compared using Statistical Parametric Mapping two-sample t-tests. Knee adduction moments and medial tibiofemoral contact forces of both the ipsi- and contralateral leg were not significantly different compared to healthy controls. The contralateral leg showed 14% higher medial tibiofemoral contact forces compared to the ipsilateral (operated) leg during the second half of stance. During the first half of stance, the lateral tibiofemoral contact force of the contralateral leg was 39% lower and the ratio 32% lower compared to healthy controls. In contrast, during the second half of stance the forces were significantly higher (39 and 26%, respectively) compared to healthy controls. The higher ratio indicates a changed distribution whereas the increased lateral tibiofemoral contact forces indicate a higher lateral knee joint loading in the contralateral leg in OA patients after total hip replacement (THR). Musculoskeletal modeling using a detailed knee model can be useful to detect differences in the load distribution between the medial and lateral knee compartment which cannot be verified with the knee adduction moment.
Objective: Many patients with localized prostate cancer (PCa) do not immediately undergo radical prostatectomy (RP) after biopsy confirmation. The aim of this study was to investigate the influence of “time-from-biopsy-to- prostatectomy” on adverse pathological outcomes.
Materials and Methods: Between January 2014 and December 2019, 437 patients with intermediate- and high risk PCa who underwent RP were retrospectively identified within our prospective institutional database. For the aim of our study, we focused on patients with intermediate- (n = 285) and high-risk (n = 151) PCa using D'Amico risk stratification. Endpoints were adverse pathological outcomes and proportion of nerve-sparing procedures after RP stratified by “time-from-biopsy-to-prostatectomy”: ≤3 months vs. >3 and < 6 months. Medians and interquartile ranges (IQR) were reported for continuously coded variables. The chi-square test examined the statistical significance of the differences in proportions while the Kruskal-Wallis test was used to examine differences in medians. Multivariable (ordered) logistic regressions, analyzing the impact of time between diagnosis and prostatectomy, were separately run for all relevant outcome variables (ISUP specimen, margin status, pathological stage, pathological nodal status, LVI, perineural invasion, nerve-sparing).
Results: We observed no difference between patients undergoing RP ≤3 months vs. >3 and <6 months after diagnosis for the following oncological endpoints: pT-stage, ISUP grading, probability of a positive surgical margin, probability of lymph node invasion (LNI), lymphovascular invasion (LVI), and perineural invasion (pn) in patients with intermediate- and high-risk PCa. Likewise, the rates of nerve sparing procedures were 84.3 vs. 87.4% (p = 0.778) and 61.0% vs. 78.8% (p = 0.211), for intermediate- and high-risk PCa patients undergoing surgery after ≤3 months vs. >3 and <6 months, respectively. In multivariable adjusted analyses, a time to surgery >3 months did not significantly worsen any of the outcome variables in patients with intermediate- or high-risk PCa (all p > 0.05).
Conclusion: A “time-from-biopsy-to-prostatectomy” of >3 and <6 months is neither associated with adverse pathological outcomes nor poorer chances of nerve sparing RP in intermediate- and high-risk PCa patients.
MicroRNAs (miRNAs) have emerged as critical posttranscriptional regulators of the immune system, including function and development of regulatory T (Treg) cells. Although this critical role has been firmly demonstrated through genetic models, key mechanisms of miRNA function in vivo remain elusive. Here, we review the role of miRNAs in Treg cell development and function. In particular, we focus on the question what the study of miRNAs in this context reveals about miRNA biology in general, including context-dependent function and the role of individual targets vs. complex co-targeting networks. In addition, we highlight potential technical pitfalls and state-of-the-art approaches to improve the mechanistic understanding of miRNA biology in a physiological context.
Despite the success of immune checkpoint blockade in cancer, the number of patients that benefit from this revolutionary treatment option remains low. Therefore, efforts are being undertaken to sensitize tumors for immune checkpoint blockade, which includes combining immune checkpoint blocking agents such as anti-PD-1 antibodies with standard of care treatments. Here we report that a combination of chemotherapy (doxorubicin) and immune checkpoint blockade (anti-PD-1 antibodies) induces superior tumor control compared to chemotherapy and immune checkpoint blockade alone in the murine autochthonous polyoma middle T oncogene-driven (PyMT) mammary tumor model. Using whole transcriptome analysis, we identified a set of genes that were upregulated specifically upon chemoimmunotherapy. This gene signature and, more specifically, a condensed four-gene signature predicted favorable survival of human mammary carcinoma patients in the METABRIC cohort. Moreover, PyMT tumors treated with chemoimmunotherapy contained higher levels of cytotoxic lymphocytes, particularly natural killer cells (NK cells). Gene set enrichment analysis and bead-based ELISA measurements revealed increased IL-27 production and signaling in PyMT tumors upon chemoimmunotherapy. Moreover, IL-27 signaling improved NK cell cytotoxicity against PyMT cells in vitro. Taken together, our data support recent clinical observations indicating a benefit of chemoimmunotherapy compared to monotherapy in breast cancer and suggest potential underlying mechanisms.
An inventory of Sciaridae (Diptera: Sciaroidea) from a eutrophic fen and a spring brook in Viidumäe Nature Reserve (Estonia, Saaremaa Island) recorded a total of 60 species, of which 57 are new records for Estonia, including two that are new to science and described herein as Cratyna (Diversicratyna) palustricola sp. nov. (Estonia) and Sciara bryophila sp. nov. (Estonia, Finland). This has raised the number of Sciaridae known from Estonia from 6 to 63.
Although cyclophosphamide (CP) has been used successfully in the clinic for over 50 years, it has so far not been possible to elucidate the mechanism of action and to use it for improvement. This was not possible because the basis of the mechanism of action of CP, which was found by lucky coincidence, is apoptosis, the discovery of which was honored with the Nobel Prize only in 2002. Another reason was that results from cell culture experiments were used to elucidate the mechanism of action, ignoring the fact that in vivo metabolism differs from in vitro conditions. In vitro, toxic acrolein is formed during the formation of the cytotoxic metabolite phosphoreamidemustard (PAM), whereas in vivo proapoptotic hydroxypropanal (HPA) is formed. The CP metabolites formed in sequence 4-hydroxycyclophosphamide (OHCP) are the main cause of toxicity, aldophosphamide (ALDO) is the pharmacologically active metabolite and HPA amplifies the cytotoxic apoptosis initiated by DNA alkylation by PAM. It is shown that toxicity is drastically reduced but anti-tumor activity strongly increased by the formation of ALDO bypassing OHCP. Furthermore, it is shown that the anti-tumor activity against advanced solid P388 tumors that grow on CD2F1 mice is increased by orders of magnitude if DNA damage caused by a modified PAM is poorly repairable. View Full-Text
All extant species of the planthopper genus Limois Stål (Hemiptera: Fulgoromorpha: Fulgoridae) were studied. One new species, Limois sordida sp. nov., is described and illustrated from China. Six known species are re-described and photos and illustrations of male genitalia are provided. A key to all extant species of this genus is also given.
Motivation: Calculating the magnitude of treatment effects or of differences between two groups is a common task in quantitative science. Standard effect size measures based on differences, such as the commonly used Cohen's, fail to capture the treatment-related effects on the data if the effects were not reflected by the central tendency. The present work aims at (i) developing a non-parametric alternative to Cohen’s d, which (ii) circumvents some of its numerical limitations and (iii) involves obvious changes in the data that do not affect the group means and are therefore not captured by Cohen’s d.
Results: We propose "Impact” as a novel non-parametric measure of effect size obtained as the sum of two separate components and includes (i) a difference-based effect size measure implemented as the change in the central tendency of the group-specific data normalized to pooled variability and (ii) a data distribution shape-based effect size measure implemented as the difference in probability density of the group-specific data. Results obtained on artificial and empirical data showed that “Impact”is superior to Cohen's d by its additional second component in detecting clearly visible effects not reflected in central tendencies. The proposed effect size measure is invariant to the scaling of the data, reflects changes in the central tendency in cases where differences in the shape of probability distributions between subgroups are negligible, but captures changes in probability distributions as effects and is numerically stable even if the variances of the data set or its subgroups disappear.
Conclusions: The proposed effect size measure shares the ability to observe such an effect with machine learning algorithms. Therefore, the proposed effect size measure is particularly well suited for data science and artificial intelligence-based knowledge discovery from big and heterogeneous data.
The subfamily Bromelioideae is one of the most diverse groups among the neotropical Bromeliaceae. Previously, key innovations have been identified which account for the extraordinary radiation and species richness of this subfamily, especially in the so-called core Bromelioideae. However, in order to extend our understanding of the evolutionary mechanisms, the genomic mechanisms (e.g. polyploidy, dysploidy) that potentially underlie this accelerated speciation also need to be tested. Here, using PI and DAPI staining and flow cytometry we estimated genome size and GC content of 231 plants covering 30 genera and 165 species and combined it with published data. The evolutionary and ecological significance of all three genomic characters was tested within a previously generated dated phylogenetic framework using ancestral state reconstructions, comparative phylogenetic methods, and multiple regressions with climatic variables. The absolute genome size (2C) of Bromelioideae varied between 0.59 and 4.11 pg, and the GC content ranged between 36.73 and 41.43%. The monoploid genome sizes (Cx) differed significantly between core and early diverging lineages. The occurrence of dysploidy and polyploidy was, with few exceptions, limited to the phylogenetically isolated early diverging tank-less lineages. For Cx and GC content Ornstein–Uhlenbeck models outperformed the Brownian motion models suggesting adaptive potential linked to the temperature conditions. 2C-values revealed different rates of evolution in core and early diverging lineages also related to climatic conditions. Our results suggest that polyploidy is not associated with higher net diversification and fast radiation in core bromelioids. On the other hand, although coupled with higher extinction rates, dysploidy, polyploidy, and resulting genomic reorganizations might have played a role in the survival of the early diverging bromelioids in hot and arid environments.
Cognitive flexibility – the ability to adjust one’s behavior to changing environmental demands – is crucial for controlled behavior. However, the term ‘cognitive flexibility’ is used heterogeneously, and associations between cognitive flexibility and other facets of flexible behavior have only rarely been studied systematically. To resolve some of these conceptual uncertainties, we directly compared cognitive flexibility (cue-instructed switching between two affectively neutral tasks), affective flexibility (switching between a neutral and an affective task using emotional stimuli), and feedback-based flexibility (non-cued, feedback-dependent switching between two neutral tasks). Three experimental paradigms were established that share as many procedural features (in terms of stimuli and/or task rules) as possible and administered in a pre-registered study plan (N = 100). Correlation analyses revealed significant associations between the efficiency of cognitive and affective task switching (response time switch costs). Feedback-based flexibility (measured as mean number of errors after rule reversals) did not correlate with task switching efficiency in the other paradigms, but selectively with the effectiveness of affective switching (error rate costs when switching from neutral to emotion task). While preregistered confirmatory factor analysis (CFA) provided no clear evidence for a shared factor underlying the efficiency of switching in all three domains of flexibility, an exploratory CFA suggested commonalities regarding switching effectiveness (accuracy-based switch costs). We propose shared mechanisms controlling the efficiency of cue-dependent task switching across domains, while the relationship to feedback-based flexibility may depend on mechanisms controlling switching effectiveness. Our results call for a more stringent conceptual differentiation between different variants of psychological flexibility.
Aerobic and resistance exercise acutely increase cognitive performance (CP). High-intensity functional training (HIFT) combines the characteristics of both regimes but its effect on CP is unclear. Thirty-five healthy individuals (26.7 ± 3.6 years, 18 females) were randomly allocated to three groups. The first (HIFT) performed a functional whole-body workout at maximal effort and in circuit format, while a second walked at 60% of the heart rate reserve (WALK). The third group remained physically inactive reading a book (CON). Before and after the 15-min intervention period, CP was assessed with the Stroop Test, Trail Making Test and Digit Span Test. Repeated-measures ANOVAs and post-hoc 95% confidence intervals (95% CI) were used to detect time/group differences. A significant group*time interaction was found for the backwards condition of the Digit Span Test (p = 0.04) and according to the 95% CI, HIFT was superior to WALK and CON. Analysis of the sum score of the Digit Span Test and the incongruent condition of the Stroop Test, furthermore, revealed main effects for time (p < 0.05) with HIFT being the only intervention improving CP. No differences were found for the Trail Making Test (p > 0.05). In conclusion, HIFT represents an appropriate method to acutely improve working memory, potentially being superior to moderate aerobic-type exercise.
Chaetopterus is a globally distributed genus of marine Annelida with a long history of taxonomic confusion. Here, we describe Chaetopterus bruneli sp. nov. from a depth of 350 m in the St. Lawrence Estuary, eastern Canada. The new species represents the northernmost record for Chaetopterus in the western Atlantic to date. The similar European species Chaetopterus norvegicus M. Sars, 1835 is resurrected from long-standing synonymy and redescribed from type material, and a lectotype is designated.
We review the species of Bidessus of Madagascar and describe Bidessus anjozorobe sp. nov. from material collected in Anjozorobe forest. Anjozorobe is part of the Anjozorobe-Angavo Protected Area, which is an important corridor of transition forest between typical eastern humid forests and the residual sub-humid forest of the Central Highlands. Bidessus longistriga Régimbart, 1895 and Bidessus perexiguus Kolbe, 1883 are widespread but endemic low-altitude species on Madagascar. Bidessus nesioticus Guignot, 1956 is an alpine species described from near the peak of the Ankaratra mountain massifs at 2500 m a.s.l. We recollected the species for the first time since its description, in Ankaratra and in a new area above 2000 m a.s.l. in the Andringitra mountain further south. Bidessus cf. nero Gschwendtner, 1933 is tentatively recorded for Madagascar for the first time but further studies are needed to test the status of mainland and insular populations. Bidessus apicidens Biström & Sanfilippo, 1986 has not been recollected on Madagascar since 1970. All species are endemic to Madagascar except potentially Bidessus cf. ceratus and Bidessus cf. nero described from Uganda and the Democratic Republic of the Congo, respectively. The older records of the two non-endemic species Bidessus complicatus Sharp, 1904 and Bidessus ovoideus Régimbart, 1895 on Madagascar could not be verified.
Background: The currently prevailing global threat of COVID-19 caused the publication numbers on coronaviruses to explode. The awareness of the scientific and public community is enormous. But what about the sense of all these undertakings and what can be learned about the future for a better understanding? These questions were answered with established bibliometric analyses of the time until the avalanche of publications unfolded.
Methods: Chronological, geographical aspects of publication output on coronavirus were also evaluated under the influence of epidemiological and socio-economic parameters.
Results: The trend in publication and citation numbers shows the strong influence of the past pandemics SARS and MERS with an untypical decline afterward. Research is becoming increasingly multidisciplinary over time. The USA and China, as the countries with the highest number of publications, are being displaced by other countries in the consideration of socio-economic and epidemiological aspects, which shows the effect of regional interest in corona research. A significant correlation was found between the number of SARS cases per country and related publications, while no correlation was found for MERS cases and articles.
Conclusions: The results underline the need for sustainable and forward-looking approaches that should not end with the containment of COVID-19.
Corrigendum zu: Memory studies 13.2020, issue: 5, S. 861-874, doi:10.1177/1750698020943014, ISSN 1750-6999
This afterword addresses the complex temporal and global dynamics of the coronavirus pandemic. After considering some of the new social rhythms that have emerged in the wake of Covid-19 around the world, it turns to the role of collective memory before, during and after corona. The aim is to provide a basic grid for how the Covid-19 pandemic could be addressed using memory studies expertise and concepts such as premediation, memorability, memory (ab)use, national memory, colonial memory, racial stereotypes, the digital archive, generational memory, or Anthropocene time.
Species are often presumed to be apparent in nature, but in practice they may be difficult to recognise, especially when viewed across continents rather than within a single site. Coalescent-based Poisson-tree-process (PTP) models applied to fast-evolving genes promise one quantitative criterion for recognising species, complete with the estimates of uncertainty that are required of a scientific method. Such methods face challenges especially in discerning between widespread polytypic species and complexes of closely related, restricted-range species. In particular, ‘over-sampling’ of many closely related individuals within one species could risk causing groups of less closely-related individuals within other species appearing relatively more distinct and consequently could risk them being interpreted falsely as separate species. Some of the most persistent taxonomic problems among bumblebees (genus Bombus Latreille, 1802) are within the subgenus Melanobombus von Dalla Torre, 1880. For a global revision of Melanobombus species, we use COI barcodes and seek to reduce the risk from localised over-sampling by filtering the data to include only unique haplotypes. Unique haplotypes give more conservative results than unfiltered data, but still increase the number of species in comparison with recent morphological treatments. After integrative assessment of COI coalescents in comparison with morphological groups, the number of accepted species shows a non-linear increase with sample size that plateaus to an increase of 47% (to 25 species) compared with a previous estimate (of 17) based on morphology alone. For the most widespread and variable species-complexes, our revised species improve the match to the patterns expected of species, both for genetic divergence-with-distance and for sympatry, leading to three main inferences. (1) The particularly widespread polytypic Bombus sichelii Radoszkowski, 1859, is a single species. (2) We detect two candidates for species within previous broad concepts of each of the former B. lapidarius (Linnaeus, 1758), B. miniatus Bingham, 1897, and B. rufofasciatus Smith, 1852. Within B. lapidarius s. lat. we find insufficient evidence to corroborate the candidate species, with no coalescent or morphological support for a recent claim for a separate species, B. bisiculus Lecocq, Biella, Martinet & Rasmont, 2019 described from southern Italy, but rather we find a weak and uncorroborated coalescent for a different and much broader group of samples from across southeastern Europe but excluding Turkey. Within the former broad concepts of B. miniatus s. lat. and B. rufofasciatus s. lat. the coalescent evidence is stronger and subtle evidence from morphology corroborates recognising B. miniatus s. str. and B. eurythorax Wang, 1892 stat. rev. as separate species as well as B. rufofasciatus s. str. and B. prshewalskyi Morawitz, 1880 stat. rev. as separate species. (3) Our coalescent and morphological results ‘split’ more clearly what has long been interpreted as a single polytypic B. keriensis Morawitz, 1887, s. lat., by supporting novel concepts of the restricted-range species: B. alagesianus Reinig, 1930 stat. rev., B. incertoides Vogt, 1911 stat. rev., B. keriensis s. str., B. qilianensis sp. nov., B. separandus Vogt, 1909 stat. rev., and B. tibeticus sp. nov. A lectotype is designated for the name B. keriensis and a neotype is designated for the name B. alagesianus. We estimate the phylogeny of Melanobombus species by including three slower-evolving genes to provide more evidence for deeper relationships, to estimate the time calibration of this phylogeny, and to estimate ancestral distributions, all within a Bayesian framework. We provide the first keys for identifying all of the species of Melanobombus.
The World Wide Web is increasing the number of freely accessible textual data, which has led to an increasing interest in research in the field of computational linguistics (CL). This area of research addresses theoretical research to answer the question of how language and knowledge must be represented in order to understand and produce language. For this purpose, mathematical models are being developed to capture the phenomena at various levels in human languages. Another field of research experiencing an increase in interest that is closely related to CL is Natural Language Processing (NLP), which is primarily concerned with developing effective and efficient data structures and algorithms that implement the mathematical models of CL.
With increasing interest in these areas, NLP tools are rapidly and frequently being developed incorporating different CL models to handle different levels of language. The open source trend has benefited all those in the scientific community who develop and use these tools. Due to yet undefined I/O standards for NLP, however, the rapid growth leads to a heterogeneous NLP landscape in which the specializations of the tools cannot benefit from each other because of interface incompatibility. In addition, the constantly growing amount of freely accessible text data requires a high-performance processing solution. This performance can be achieved by horizontal and vertical scaling of hardware and software. For these reasons the first part of this thesis deals with the homogenization of the NLP tool landscape, which is achieved by a standardized framework called TextImager. It is a cloud computing based multi-service, multi-server, multi-pipeline, multi-database, multi-user, multi-representation and multi-visual framework that already provides a variety of tools for various languages to process various levels of linguistic complexity. This makes it possible to answer research questions that require the processing of a large amount of data at several linguistic levels.
The integrated tools and the homogenized I/O data streams of the TextImager make it possible to combine the built-in tools in two dimensions: (1) the horizontal dimension to achieve NLP task-specific improvement (2) the orthogonal dimension to implement CL models that are based on multiple linguistic levels and thus rely on a combination of different NLP tools. The second part of this thesis therefore deals with the creation of models for the horizontal combination of tools in order to show the possibilities for improvement using the example of the NLP task of Named Entity Recognition (NER). The TextImager offers several tools for each NLP task, most of which have been trained on the same training basis, but can produce different results. This means that each of the tools processes a subset of the data correctly and at the same time makes errors in another subset. In order to process as large a subset of the data as possible correctly, a horizontal combination of tools is therefore required. Machine learning-based voting mechanisms called LSTMVoter and CRFVoter were developed for this purpose, which allow a combination of the outputs of individual NLP tools so that better partial data results can be achieved. In this thesis the benefit of Voter is shown using the example of the NER task, whose results flow
back into the TextImager tool landscape.
The third part of this thesis deals with the orthogonal combination of TextImager tools to accomplish the verb sense disambiguation (VSD). The CL question is investigated, how verb senses should be modelled in order to disambiguate them computatively. Verbsenses have a syntagmatic-paradigmatic relationship with surrounding words. Therefore, preprocessing on several linguistic levels and consequently an orthogonal combination of NLP tools is required to disambiguate verbs on a computational level. With TextImager’s integrated NLP landscape, it is now possible to perform these preprocessing steps to induce the information needed for the VSD. The newly developed NLP tool for the VSD has been integrated into the TextImager tool landscape, enabling the analysis of a further linguistic level.
This thesis presents a framework that homogenizes the NLP tool landscape in a cluster-based way. Methods for combining the integrated tools are implemented to improve the analysis of a specific linguistic level or to develop tools that open up new linguistic levels.
Während meiner Promotion habe ich zwei Projekte unter der Aufsicht von Dr. Misha Kudryashev durchgeführt. Im ersten Projekt habe ich die Strukturen des Ryanodinrezeptors 1 (RyR1) in Apo- und Ryanodin-Bindungszuständen in der nativen Membran durch Tomographie und Subtomogramm-Mittelung bei 12,6 bzw. 17,5 Å bestimmt. Im Vergleich zur Struktur von gereinigtem RyR1 unter Verwendung der Einzelpartikel-Kryo-Elektronenmikroskopie (Cryo-EM) können zusätzliche Dichten in der cytoplasmatischen Domäne und der sarkoplasmatischen Retikulum (SR)-Membran bzw. im SR-Lumen beobachtet werden. Die Auflösung der Struktur von RyR1 im Apo-Zustand wurde von den Kollegen in meinem Labor mithilfe der Hybridmethode auf 9,5 Å verbessert. Diese Arbeit hat unser Verständnis für die Mechanismen von RyR1 in nativen Membranen erweitert. Im zweiten Projekt habe ich die Struktur des Proteins SdeC der SidE-Familie durch Einzelpartikel-Kryo-EM bei 4,6 Å bestimmt. Die Kristallstruktur des C-Terminus von SdeA wurde von meinem Forschungspartner Dr. Mohit Misra gelöst. Durch Überlagerung einer gemeinsamen Helix dieser beiden Strukturen konnten wir ein kombiniertes Modell erstellen und ein allgemeines Verständnis der Proteine der SidE-Familie erhalten.
We present a comprehensive revision of the pholcid spider collection of M.A. González-Sponga, who between 1998 and 2011 described 22 new genera and 51 new species of Pholcidae from Venezuela. In addition, we treat the pholcid material collected during three expeditions to Venezuela conducted between 2002 and 2020. Of González-Sponga’s pholcid taxa we recognize three genera and 24 species as valid. We describe 43 new species (all from males and females) in one new and 13 previously described genera; four genera are newly recorded for Venezuela. We describe the previously unknown females of 15 species, present new records for 46 previously described species, synonymize one genus and one species, and correct numerous minor errors in previous publications on Venezuelan pholcids. At the generic level, the Venezuelan pholcid fauna now appears fairly well known, but available data on distribution and endemism suggest that many species remain undiscovered and undescribed. Despite the obvious gaps, our data are congruent with previous studies on other taxa that have the highest levels of endemism in the Venezuelan Andes, the Coastal Ranges, and the Guyana Highlands. The Falcón Region in particular shows a complex mosaic of biogeographic relationships with other regions. We provide new biological data on numerous species. We document the first cases of evolutionary microhabitat shifts in the genera Mecolaesthus Simon, 1893 and Priscula Simon, 1893. We document several cases of close congeners sharing localities, usually in slightly to conspicuously different microhabitats, sometimes apparently in identical microhabitats. We document several cases of color polymorphism, mostly intersexual, in Metagonia conica (Simon, 1893) both intersexual and among males. We document further cases of two rare phenomena in Pholcidae: use of specific non-silken structures for retreats (in Pisaboa Huber, 2000) and egg parasitism (in Priscula).
Objective: To evaluate if 3 peptides derived from the cartilage oligomeric matrix protein (COMP), which wounded zones of cartilage secrete into synovial fluid, possess biological activity and might therefore be involved in the regulation of specific aspects of joint regeneration.
Methods: The 3 peptides were produced by chemical synthesis and then tested in vitro for known functions of the COMP C-terminal domain from which they derive, and which are involved in osteoarthritis: transforming growth factor-β (TGF-β) signaling, vascular homeostasis, and inflammation. Results. None of the peptides affected the gene expression of COMP in osteochondral progenitor cells (P > 0.05). We observed no effects on the vascularization potential of endothelial cells (P > 0.05). In cultured synovium explants, no differences on the expression of catabolic enzymes or proinflammatory cytokines were found when peptides were added (P > 0.05).
Discussion and conclusions: The 3 peptides tested do not regulate TGF-β signaling, angiogenesis and vascular tube formation, or synovial inflammation in vitro and therefore most likely do not play a major role in the disease process.
Background: The number of implantable cardioverter defibrillator (ICD) infections is increasing due to an increased number of ICD implants, higher-risk patients, and more frequent replacement procedures, which carry a higher risk of infection. Reducing the morbidity, mortality, and cost of ICD-related infections requires an understanding of the current rate of this complication and its predictors.
Methods: The Shock Implant Evaluation Trial (SIMPLE) trial randomized 2500 ICD recipients to defibrillation testing or not. Over an average of 3.1 years, patients were seen every 6 months and examined for evidence of ICD infection, which was defined as requiring device removal and/or intravenous antibiotics.
Results: Within 24 months, 21 patients (0.8%) developed infection. Fourteen patients (67%) with infection presented within 30 days, 20 patients by 12 months, and only 1 patient beyond 12 months. Univariate analysis demonstrated that patients with primary electrical disorders (3 patients, P = 0.009) and those with a secondary prevention indication (13 patients, P = 0.0009) were more likely to develop infection. Among the 2.2% of patients who developed an ICD wound hematoma, 10.4% developed an infection. Among the 8.3% of patients requiring an ICD reintervention, 1.9% developed an infection.
Conclusions: This cohort of ICD recipients at high-volume centres have a low risk of device-related infection. However; strategies to reduce wound hematoma and the need for ICD reintervention could further reduce the rate of infection.
This article reports an investigation of how inhibition contributes to fluid reasoning when it is decomposed into the reasoning ability, item-position, and speed components to control for possible method effects. Working memory was also taken into consideration. A sample of 223 university students completed a fluid reasoning scale, two tasks tapping prepotent response inhibition, and two working memory tasks. Fixed-links modeling was used to separate the effect of reasoning ability from the effects of item-position and speed. The goodness-of-fit results confirmed the necessity to consider the reasoning ability, item-position, and speed components simultaneously. Prepotent response inhibition was only associated with reasoning ability. This association disappeared when working memory served as a mediator. Taken together, these results reflect the inhomogeneity of what is tapped by the fluid reasoning scale on one hand and, on the other, suggest inhibition as an important component of working memory.
Purpose: Acute kidney injury (AKI) is a severe complication in medical and surgical intensive care units accounting for a high morbidity and mortality. Incidence, risk factors, and prognostic impact of this deleterious condition are well established in this setting. Data concerning the neurocritically ill patients is scarce. Therefore, aim of this study was to determine the incidence of AKI and elucidate risk factors in this special population.
Methods: Patients admitted to a specialized neurocritical care unit between 2005 and 2011 with a length of stay above 48 hours were analyzed retrospectively for incidence, cause, and outcome of AKI (AKI Network-stage ≥2).
Results: The study population comprised 681 neurocritically ill patients from a mixed neurosurgical and neurological intensive care unit. The prevalence of chronic kidney disease (CKD) was 8.4% (57/681). Overall incidence of AKI was 11.6% with 36 (45.6%) patients developing dialysis-requiring AKI. Sepsis was the main cause of AKI in nearly 50% of patients. Acute kidney injury and renal replacement therapy are independent predictors of worse outcome (hazard ratio [HR]: 3.704; 95% confidence interval [CI]: 1.867-7.350; P < .001; and HR: 2.848; CI: 1.301-6.325; P = .009). Chronic kidney disease was the strongest independent risk factor (odds ratio: 12.473; CI: 5.944-26.172; P < .001), whereas surgical intervention or contrast agents were not associated with AKI.
Conclusions: Acute kidney injury in neurocritical care has a high incidence and is a crucial risk factor for mortality independently of the underlying neurocritical condition. Sepsis is the main cause of AKI in this setting. Therefore, careful prevention of infectious complications and considering CKD in treatment decisions may lower the incidence of AKI and hereby improve outcome in neurocritical care.
On the basis of the economic theory of network effects, this article provides a novel explanation of the so-called patent paradox, i.e. the question why the propensity to patent is so strong when the expected average value of most patents is low. It demonstrates that the patent system of a country resembles a telephone network or a social media platform. Patents are perceived as nodes in a virtual network that, as a whole, exhibits network effects. It is explained why patents are not independent of other patents but that they complement each other in several ways both within and beyond markets and fields of technology, and that patents thus create synchronization value over and above individual interests of patent holders in exclusivity. As a consequence, the more patents there are, the more valuable it is to also seek patents, and vice versa. Since patents thus display increasing returns to adoption, the willingness to pay for the next patent slopes upwards. This explains why, after a phase of early instability and a certain tipping point, many countries’ patent systems expanded quickly and eventually became a rigid standard (“lock-in”). The concluding section raises the question what regulatory measures are suitable to effectively address the ensuing anticommons effects.
The long-standing battle between economic nationalism and globalism has again taken center stage in geopolitics. This article applies this dichotomy to the law and policy of international intellectual property (IP). Most commentators see IP as a prime example of globalization. The article challenges this view on several levels. In a nutshell, it claims that economic nationalist concerns about domestic industries and economic development lie at the heart of the global IP system. To support this argument, the article summarizes and categorizes IP policies adopted by selected European countries, the European Union, and the U.S. Section I presents three types of inbound IP policies that aim to foster local economic development and innovation. Section II adds three versions of outbound IP policies that, in contrast, target foreign countries and markets. Concluding section III traces a dialectic virtuous circle of economic nationalist motives leading to global legal structures and identifies the function and legal structure of IP as the reason for the resilience and even dominance of economic nationalist motives in international IP politics. IP concerns exclusive private rights that are territorially limited creatures of (supra-)national statutes. These legal structures make up the economic nationalist DNA of IP.
This paper treats the planthopper genus, Atracis Stål, 1866 (Flatidae: Flatoidinae) in China. Five new species, A. ocularia sp. nov., A. patefacta sp. nov., A. punctulata sp. nov., A. sphaerica sp. nov. and A. ungulata sp. nov., are described and a checklist of all its known species from China is provided.
Nemaspela Šilhavý, 1966 (Opiliones: Nemastomatidae) is a genus of exclusively troglobiotic harvestmen species inhabiting caves in the Crimea, Caucasus and Balkan Peninsula. In this paper, Nemaspela borkoae sp. nov., recently found in four caves in Montenegro, is described. The new species is characterized by its small body, 1.5–2.1 mm long, and very long, thin appendages, with legs II about 15 times as long as the body. Although very similar, Nemaspela ladae Karaman, 2013 and N. borkoae sp. nov. can be easily distinguished by the terminally rounded vs conical glans, straight vs conspicuously ventrally bent pedipalp tarsus on its proximal portion and pedipalp tarsus measuring about ½ vs ⅔ tibia length. Nemaspela ladae and N. borkoae sp. nov. constitute the western Nemaspela group, both missing the male cheliceral apophysis present in all species of the eastern Nemaspela group from the Crimea and Caucasus, except in N. femorecurvata Martens, 2006. However, according to the glans morphology, N. borkoae sp. nov. seems much more closely related to several species from the Caucasus than to N. ladae from the Balkan Peninsula. We speculate that N. ladae and N. borkoae sp. nov. might originate from two epigean ancestral lineages.
The genus Teloneria Aczél, 1954 is resurrected from synonymy with Chaetonerius Hendel, 1913 to include four species: Teloneria apicata (Edwards, 1919) comb. nov., Teloneria bimaculata (Edwards, 1919) comb. nov., Teloneria juceliae Sepúlveda & Souza sp. nov. and Teloneria ladyae Sepúlveda & Souza sp. nov. Lectotypes for Telostylus apicatus Edwards, 1919 and its junior synonym, Telostylinus apicalis Enderlein, 1922, and for Telostylinus ornatipennis Enderlein, 1922, junior synonym of Teloneria bimaculata comb. nov., are designated. An identification key to Chaetonerius, Telostylus Bigot, 1859 and Teloneria, with emphasis on the identification of the species of Teloneria, illustrations and distribution data are provided.