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Following up on earlier investigations, the present paper analyzes construct validity of the impostor phenomenon. It examines the question whether the impostor phenomenon is a homogeneous construct or whether different types of persons with impostor self-concept can be distinguished on the basis of related characteristics. The study was conducted with professionals in leadership positions exhibiting a pronounced impostor self-concept (n = 183). Cluster-analytic procedures indicated the existence of two different types: one group which, in line with the literature (e.g., Clance, 1985), possessed traits classified as fairly unfavorable (“true impostors”) and another group which can be described as largely unencumbered (“strategic impostors”). The present study suggests two types of impostorism: “True” impostors characterized by the negative self-views associated with the construct definition, and more “strategic” impostors who seem to be less encumbered by self-doubt. It is assumed that “strategic impostors” are characterized by a form of deliberate self-presentation. Therefore, the impostor self-concept cannot principally be viewed as a dysfunctional personality style. This distinction should be more carefully considered in further research and in therapeutic interventions.
Autism spectrum disorders (ASD) and attention-deficit/hyperactivity disorder (ADHD) frequently co-occur. The presence of a genetic link between ASD and ADHD symptoms is supported by twin studies, but the genetic overlap between clinically ascertained ASD and ADHD remains largely unclear. We therefore investigated how ASD and ADHD co-aggregate in individuals and in families to test for the presence of a shared genetic liability and examined potential differences between low- and high-functioning ASD in the link with ADHD. We studied 1 899 654 individuals born in Sweden between 1987 and 2006. Logistic regression was used to estimate the association between clinically ascertained ASD and ADHD in individuals and in families. Stratified estimates were obtained for ASD with (low-functioning) and without (high-functioning) intellectual disability. Individuals with ASD were at higher risk of having ADHD compared with individuals who did not have ASD (odds ratio (OR)=22.33, 95% confidence interval (CI): 21.77–22.92). The association was stronger for high-functioning than for low-functioning ASD. Relatives of individuals with ASD were at higher risk of ADHD compared with relatives of individuals without ASD. The association was stronger in monozygotic twins (OR=17.77, 95% CI: 9.80–32.22) than in dizygotic twins (OR=4.33, 95% CI: 3.21–5.85) and full siblings (OR=4.59, 95% CI: 4.39–4.80). Individuals with ASD and their relatives are at increased risk of ADHD. The pattern of association across different types of relatives supports the existence of genetic overlap between clinically ascertained ASD and ADHD, suggesting that genomic studies might have underestimated this overlap.
In the title compound, C17H18N2O, the central carbon atom with the OH substituent and one of the (E)-benzylideneamino substituents are disordered over two sets of sites with occupancies of 0.851 (4) and 0.149 (4). The relative positions of the two disorder components is equivalent to a rotation of approximately 60° about the C—N single bond. In the crystal, the molecules are held together by O—H...N hydrogen bonds, forming simple C(5) chains along the b-axis direction. In addition, pairs of the chains are further aggregated by weak C—H...π interactions.
Mathematical models of virus dynamics have not previously acknowledged spatial resolution at the intracellular level despite substantial arguments that favor the consideration of intracellular spatial dependence. The replication of the hepatitis C virus (HCV) viral RNA (vRNA) occurs within special replication complexes formed from membranes derived from endoplasmatic reticulum (ER). These regions, termed membranous webs, are generated primarily through specific interactions between nonstructural virus-encoded proteins (NSPs) and host cellular factors. The NSPs are responsible for the replication of the vRNA and their movement is restricted to the ER surface. Therefore, in this study we developed fully spatio-temporal resolved models of the vRNA replication cycle of HCV. Our simulations are performed upon realistic reconstructed cell structures—namely the ER surface and the membranous webs—based on data derived from immunostained cells replicating HCV vRNA. We visualized 3D simulations that reproduced dynamics resulting from interplay of the different components of our models (vRNA, NSPs, and a host factor), and we present an evaluation of the concentrations for the components within different regions of the cell. Thus far, our model is restricted to an internal portion of a hepatocyte and is qualitative more than quantitative. For a quantitative adaption to complete cells, various additional parameters will have to be determined through further in vitro cell biology experiments, which can be stimulated by the results deccribed in the present study.
Taxonomy, phylogeny and zoogeography of the hexaploid Torini of the Middle East and North Africa
(2017)
Fishes of the tribe Torini Karaman, 1971 (Teleostei: Cyprinidae) are a diverse group of primary freshwater fishes, distributed in Africa, the Middle East, and Indomalaya. They are an important component of the native freshwater-fish fauna of the Middle East and North Africa, and occur in most large river systems of the Levant, Arabia, Mesopotamia, southern Iran, and Morocco. They belong to the subfamily Cyprininae, are characterised by being tetraploid or hexaploid, having large scales, and a smooth and ossified last unbranched ray in the dorsal fin. As primary freshwater fishes they are not able to tolerate marine conditions and depend on direct freshwater connections for their dispersal. This makes them an ideal model for zoogeographic studies.
Prior to this study, the diversity of the Torini species in the Middle East and North Africa was not well understood. The validity of several genera and species was unclear, and the generic assignment of several species changed frequently.
In this PhD project the taxonomy, phylogeny, and zoogeography of the Torini of the Middle East and North Africa were investigated with morphological, as well as molecular methods. More than 1550 fish specimens were examined morphologically. Some of the specimens, including the types of most nominal species, were already available from museum collections. The remaining specimens were collected during expeditions to Ethiopia, Iran, Jordan, Morocco and Syria. Tissue samples were collected for molecular genetic analyses. The mitochondrial genes for cytochrome b, NADH dehydrogenase subunit 4 and the tRNAs for serine and histidine were sequenced from more than 120 specimens, representing 20 species of Torini and two small, diploid African barbs (Cyprinidae, tribe Smiliogastrini). Molecular data were analysed with Bayesian inference and other methods.
The analyses confirmed that the hexaploid Torini of Africa and the Middle East form a monophyletic group. In the Middle East and North Africa the Torini are represented by the genera Arabibarbus, Carasobarbus, Mesopotamichthys, and Pterocapoeta. These genera are each morphologically diagnosable, monophyletic, and genetically distinct. The species 'Labeobarbus' reinii cannot be assigned to any of these genera, because it is morphologically dissimilar and genetically clearly separated from each of them. A generic name for this species is presently not available and until the description of a new genus it is preliminarily assigned to the genus 'Labeobarbus'.
Out of the 28 species-group taxa described from the Middle East and North Africa until now, 15 are valid: Arabibarbus arabicus, A. grypus, A. hadhrami, Carasobarbus apoensis, C. canis, C. chantrei, C. exulatus, C. fritschii, C. harterti, C. kosswigi, C. luteus, C. sublimus, Mesopotamichthys sharpeyi, Pterocapoeta maroccana, and 'Labeobarbus' reinii.
The phylogenetic relationships between the Middle Eastern and North African Torini are well resolved, based on the analysis of mitochondrial DNA sequences from nearly all relevant species.
The interspecific and intraspecific morphological and genetic diversity is shaped by the zoogeographic history. Conclusions can be drawn about the events that shaped the evolution of this group. The Torini originated in the Indomalayan biogeographical realm and colonised the Middle East and Africa during the Miocene via the Gomphotherium landbridge. The Indomalayan Torini are tetraploid, whereas those of the Middle East and Africa are hexaploid. Molecular phylogenetic analyses showed that the hexaploid Torini cluster within the tetraploid Torini. This makes the tetraploid Torini a paraphyletic group with respect to the hexaploid Torini. Morocco was colonised in two independent waves. The first came from sub-Saharan Africa and is represented by Pterocapoeta maroccana. The second originated in the Middle East and gave rise to C. fritschii, C. harterti, and probably 'L.' reinii. The Tigris-Euphrates system is the largest freshwater system in the Middle East. Its central position between the Orontes River and Jordan River in the West, the Iranian tributaries to the Persian Gulf in the East, and the Arabian Peninsula in the South made it an important crossroad for the colonisation of the Middle East by Torini and other freshwater biota. During the Miocene the predecessors of the Jordan and Orontes rivers were connected to the Tigris-Euphrates system. The Jordan River was separated from the Euphrates before the Orontes. Arabia was colonised in two waves. The first (A. arabicus, A. hadhrami, C. exulatus) dates to the Pliocene, whereas the second (C. apoensis) ended as recently as the late Pleistocene or early Holocene.
According to international and national constitutional law, indigenous peoples in most Latin American countries have the right to maintain and strengthen their distinct political, legal, economic, social and cultural institutions. As a consequence of this and of a long and ongoing process of political debate and recognition, ever more indigenous peoples are practicing their own laws, following their own cultural traditions and customs. In doing so, they often draw on history, recreating their identities and reconstructing their distinct legal pasts. At the same time, historical research has increasingly pointed out the intense interaction between indigenous peoples and European invaders during colonial period. It has become clear that it is difficult to draw a clear line between purely ‘indigenous’ and ‘colonial’ legal traditions due to the hybridisation of indigenous and colonial laws and legal practices. The aim of this paper is to introduce this historiography and its relevance to law and to present some methodological challenges in writing the history of indigenous rights in Latin America resulting from this shift in (legal) historiography.
This article addresses concerns that the growth in global governance may be bringing with it a decline in the significance of democratic sources of political legitimacy. One approach in evaluating such concerns is to ask whether the respective patterns of legitimation for private and public authority differ or whether they refer to a similar set of normative standards. Private transnational governance regimes provide useful contexts in which to assess the presumed democratic erosion. They seem, almost of themselves, to make the case for such a decline: in them regulatory authority is exercised by non-state actors who, by their very nature, lack the kind of authorization afforded by the democratic procedures that legitimize state-based regulation; in addition, they are intrinsically linked to the notion of politics as a form of problem-solving rather than as the exercise of power. Given these characteristics, when governance arrangements of this kind are subjected to criticism, one would expect justificatory responses to relate primarily to performance, with normative criteria such as fundamental individual rights and the imperative for democratic procedure playing only a minor role. On the basis of a qualitative content analysis, the study tests three ideal-type patterns of legitimation for plausibility. The case selected for examination is the recent controversy surrounding the hybrid governance regime that operates to prevent the use of performance-enhancing drugs in sport. The debate offers the possibility of a ‘nutshell’ comparison of the respective patterns of legitimation used in criticizing and justifying state and non-state regulatory authority. This comparison yields two findings. The first is that the values used to appraise the state-based components of the sporting world’s hybrid regulatory regime do not differ systematically from those used to appraise the private elements: contestation and justification in both cases are founded on normative criteria relating to fundamental individual rights and democratic procedure and not just on performance-related considerations. The second finding is that justificatory grounds of the first type do not appear to be diminishing in importance vis-à-vis those of the second.
Corporatist regulation has a hybrid structure in that it covers state regulation, regulated self-regulation as well as private-public co-regulation. Notably diverging from the standard mode of state regulation, such arrangements required a higher degree of legitimation. Corporatist concepts flourished in the Weimar Republic. This paper deals with three legal scholars’ considerations regarding how to legitimize corporatist models, namely Edgar Tatarin-Tarnheyden, Heinrich Herrfahrdt, and Friedrich Glum. Their institutional touchstone was the Imperial Economic Council, as provided for by article 165 of the Weimar Constitution. This article envisioned a multi-level system of economic councils ranging from regional economic councils up to the Imperial Economic Council and involving representatives of all occupational groups in the performance of state tasks. However, only a Provisional Imperial Economic Council, with a restricted consultative remit, was ever actually established. Based on this model, Tatarin-Tarnheyden, Heinrich Herrfahrdt, and Friedrich Glum conceptualized organizational structures aiming at the comprehensive inclusion of non-state actors. They were legitimized primarily with reference to their output; that is, these organizational forms were supposed to enable a more appropriate and efficient realization of public interests. The input-based argument was basically a question of participation, which implies considerable proximity to typical topoi of democratic legitimation. This similarity is perhaps counter-intuitive, given that corporatist concepts are traditionally associated with anti-democratic ideologies due to their anti-parliamentarian slant. The numerous points of convergence between corporatist and democratic thought simultaneously reflect the heterogeneity of democratic reasoning in the Weimar period and the openness for ideas that were sceptical of—or even hostile to—parliamentary democracy and the party-based state.
This thematic issue brings together research from political science and legal history about legitimacy discourses covering different forms of public–private co-regulation and private self-regulation, domestic and transnational, past and present. These forms of governance highlight the important role of non-state actors in exercising public authority. There has been a growing debate about the legitimacy of non-state actors setting and enforcing norms and providing public goods and services. However, the focus of this thematic issue is not on developing abstract criteria of legitimacy. Rather, the authors analyze legitimacy discourses around different cases of privatized or partly privatized forms of governance from the early 20th century until today. Legitimacy is subject to empirical and not normative analysis. Legitimacy discourses are analyzed in order to shed light on the legitimacy conceptions that actors hold, what they consider as legitimate institutions, and based on what criteria. The particular focus of this thematic issue is to examine whether the significance of democratic legitimacy is decreasing as the importance of regulation exercised by private actors is increasing.
Die Reihe „Papers of Excellence 2.0: Ausgewählte Arbeiten aus den Fachdidaktiken und Bildungswissenschaften der Goethe-Universität Frankfurt a.M.“ ist eine neue, erweiterte und zusätzliche Auflage der bekannten Reihe „Papers of Excellence: Ausgewählte Arbeiten aus den Fachdidaktiken“, welche seit 2010 von Daniela Elsner und Anja Wildemann im Shaker-Verlag herausgegeben wird. In alter Tradition werden auch in der ab sofort zusätzlich zur Printausgabe erscheinenden Online Version dieser Buchreihe herausragende Examens- und Masterarbeiten, die sich durch eine ausgewiesene empirische, fachdidaktische Auseinandersetzung mit einem Thema auszeichnen, zusammenfassend vorgestellt. Neu ist, dass die Online Version nun auch Arbeiten mit einem bildungswissenschaftlichen Fokus aufnimmt und solche, die an der Schnittstelle zwischen Fachdidaktik und Bildungswissenschaften an-gelegt sind. Die Papers of Excellence 2.0, die derzeit nur Studien integriert, die an der Goethe Universität Frankfurt am Main angefertigt wurden, werden von Astrid Jurecka (Bildungswissenschaften) und Daniela Elsner (Fachdidaktik) herausgegeben und sind kostenfrei zugänglich.
The Gram-negative bacteria Photorhabdus and Xenorhabdus are known to produce a variety of different natural products (NP). These compounds play different roles since the bacteria live in symbiosis with nematodes and are pathogenic to insect larvae in the soil. Thus, a fine tuned regulatory system controlling NP biosynthesis is indispensable. Global regulators such as Hfq, Lrp, LeuO and HexA have been shown to influence NP production of Photorhabdus and Xenorhabdus. Additionally, photopyrones as quorum sensing (QS) signals were demonstrated to be involved in the regulation of NP production in Photorhabdus. In this study, we investigated the role of another possible QS signal, autoinducer-2 (AI-2), in regulation of NP production. The AI-2 synthase (LuxS) is widely distributed within the bacterial kingdom and has a dual role as a part of the activated methyl cycle pathway, as well as being responsible for AI-2 precursor production. We deleted luxS in three different entomopathogenic bacteria and compared NP levels in the mutant strains to the wild type (WT) but observed no difference to the WT strains. Furthermore, the absence of the small regulatory RNA micA, which is encoded directly upstream of luxS, did not influence NP levels. Phenotypic differences between the P. luminescens luxS deletion mutant and an earlier described luxS deficient strain of P. luminescens suggested that two phenotypically different strains have evolved in different laboratories.
Correlation of lumbar lateral recess stenosis in magnetic resonance imaging and clinical symptoms
(2017)
Aim: To assess the correlation of lateral recess stenosis (LRS) of lumbar segments L4/5 and L5/S1 and the Oswestry Disability Index (ODI).
Methods: Nine hundred and twenty-seven patients with history of low back pain were included in this uncontrolled study. On magnetic resonance images (MRI) the lateral recesses (LR) at lumbar levels L4/5 and L5/S1 were evaluated and each nerve root was classified into a 4-point grading scale (Grade 0-3) as normal, not deviated, deviated or compressed. Patient symptoms and disability were assessed using ODI. The Spearman’s rank correlation coefficient was used for statistical analysis (P < 0.05).
Results: Approximately half of the LR revealed stenosis (grade 1-3; 52% at level L4/5 and 42% at level L5/S1) with 2.2% and 1.9% respectively reveal a nerve root compression. The ODI score ranged from 0%-91.11% with an arithmetic mean of 34.06% ± 16.89%. We observed a very weak statistically significant positive correlation between ODI and LRS at lumbar levels L4/5 and L5/S1, each bilaterally (L4/5 left: rho < 0.105, P < 0.01; L4/5 right: rho < 0.111, P < 0.01; L5/S1 left: rho 0.128, P < 0.01; L5/S1 right: rho < 0.157, P < 0.001).
Conclusion: Although MRI is the standard imaging tool for diagnosing lumbar spinal stenosis, this study showed only a weak correlation of LRS on MRI and clinical findings. This can be attributed to a number of reasons outlined in this study, underlining that imaging findings alone are not sufficient to establish a reliable diagnosis for patients with LRS.
Microtubule-targeting agents (MTAs) are the most widely used chemotherapeutic drugs. Pretubulysin (PT), a biosynthetic precursor of the myxobacterial tubulysins, was recently identified as a novel MTA. Besides its strong anti-tumoral activities, PT attenuates tumor angiogenesis, exerts anti-vascular actions on tumor vessels and decreases cancer metastasis formation in vivo. The aim of the present study was to analyze the impact of PT on the interaction of endothelial and tumor cells in vitro to gain insights into the mechanism underlying its anti-metastatic effect. The influence of PT on tumor cell adhesion and transmigration onto/through the endothelium as well as its influence on cell adhesion molecules and the chemokine system CXCL12/CXCR4 was investigated. Treatment of human endothelial cells with PT increased the adhesion of breast cancer cells to the endothelial monolayer, whereas their transmigration through the endothelium was strongly reduced. Interestingly, the PT-induced upregulation of ICAM-1, VCAM-1 and CXCL12 were dispensable for the PT-evoked tumor cell adhesion. Tumor cells preferred to adhere to collagen exposed within PT-triggered endothelial gaps via β1-integrins on the tumor cell surface. Taken together, our study provides, at least in part, an explanation for the anti-metastatic potential of PT.
Background: Certain disadvantages of the standard hematopoietic stem and progenitor cell (HSPC) mobilizing agent G-CSF fuel the quest for alternatives. We herein report results of a Phase I dose escalation trial comparing mobilization with a peptidic CXCR4 antagonist POL6326 (balixafortide) vs. G-CSF.
Methods: Healthy male volunteer donors with a documented average mobilization response to G-CSF received, following ≥6 weeks wash-out, a 1–2 h infusion of 500–2500 µg/kg of balixafortide. Safety, tolerability, pharmacokinetics and pharmacodynamics were assessed.
Results: Balixafortide was well tolerated and rated favorably over G-CSF by subjects. At all doses tested balixafortide mobilized HSPC. In the dose range between 1500 and 2500 µg/kg mobilization was similar, reaching 38.2 ± 2.8 CD34 + cells/µL (mean ± SEM). Balixafortide caused mixed leukocytosis in the mid-20 K/µL range. B-lymphocytosis was more pronounced, whereas neutrophilia and monocytosis were markedly less accentuated with balixafortide compared to G-CSF. At the 24 h time point, leukocytes had largely normalized.
Conclusions: Balixafortide is safe, well tolerated, and induces efficient mobilization of HSPCs in healthy male volunteers. Based on experience with current apheresis technology, the observed mobilization at doses ≥1500 µg/kg of balixafortide is predicted to yield in a single apheresis a standard dose of 4× 10E6 CD34+ cells/kg from most individuals donating for an approximately weight-matched recipient. Exploration of alternative dosing regimens may provide even higher mobilization responses.
Trial Registration European Medicines Agency (EudraCT-Nr. 2011-003316-23) and clinicaltrials.gov (NCT01841476)
Most molecular cancer therapies act on protein targets but data on the proteome status of patients and cellular models for proteome‐guided pre‐clinical drug sensitivity studies are only beginning to emerge. Here, we profiled the proteomes of 65 colorectal cancer (CRC) cell lines to a depth of > 10,000 proteins using mass spectrometry. Integration with proteomes of 90 CRC patients and matched transcriptomics data defined integrated CRC subtypes, highlighting cell lines representative of each tumour subtype. Modelling the responses of 52 CRC cell lines to 577 drugs as a function of proteome profiles enabled predicting drug sensitivity for cell lines and patients. Among many novel associations, MERTK was identified as a predictive marker for resistance towards MEK1/2 inhibitors and immunohistochemistry of 1,074 CRC tumours confirmed MERTK as a prognostic survival marker. We provide the proteomic and pharmacological data as a resource to the community to, for example, facilitate the design of innovative prospective clinical trials.
Die vorliegende Dissertation befasst sich mit dem Umstieg von papierbasiertem (PBA) auf computerbasiertes Assessment (CBA), insbesondere in Large-Scale-Studien. In der Bildungsforschung war Papier lange Zeit das Medium für Assessments, im Zuge des digitalen Zeitalters erhält der Computer aber auch hier Einzug. So sind die großen Bildungsvergleichsstudien, wie PISA (Programme for International Student Assessment) oder PIAAC (Programme for the International Assessment of Adult Competencies), und nationalen Studien über Bildungsverläufe und -entwicklungen im Rahmen des NEPS (Nationales Bildungspanel) bereits umgestiegen oder befinden sich im Prozesses des Umstiegs von PBA auf CBA. Findet innerhalb dieser Studien ein Moduswechsel statt, dann muss die Vergleichbarkeit zwischen den Ergebnissen der unterschiedlichen Administrationsmodi gewährleistet werden. Unterschiede in den Eigenschaften der Modi, wie beispielsweise im Antwortformat, können sich dabei auf die psychometrischen Eigenschaften der Tests auswirken und zu sogenannten Modus Effekten führen. Diese Effekte wiederum können sich in Unterschieden zwischen den Testscores widerspiegeln, sodass diese nicht mehr direkt miteinander vergleichbar sind. Die zentrale Frage dabei ist, ob es durch den Moduswechsel zu einer Veränderung des gemessenen Konstruktes kommt. Ist dies der Fall, so können Testergebnisse aus unterschiedlichen Administrationsmodi nicht miteinander verglichen und die Ergebnisse aus dem computerbasierten Test nicht analog zu den Ergebnissen aus dem papierbasierten Test interpretiert werden. Auch Veränderungen, die aus Messungen zu verschiedenen Zeitpunkten und mit unterschiedlichen Modi resultieren, lassen sich dann nicht mehr beschreiben. Es kann jedoch auch Modus Effekte geben, die zwar nicht das gemessene Konstrukt betreffen, aber sich beispielsweise in der Schwierigkeit der Items niederschlagen. Solange aber das erfasste Konstrukt bei einem Moduswechsel unverändert bleibt, können diese Modus Effekte bei der Berechnung der Testscores berücksichtigt und die Vergleichbarkeit gewährleistet werden. Somit ist, nicht nur im Hinblick auf gültige Trendschätzungen, der Analyse von Modus-Effekten ein hoher Stellenwert beizumessen. Da die bisherige Befundlage in der Literatur zu Modus-Effekten sowohl hinsichtlich der Stärke der gefundenen Effekte, als auch in Bezug auf die verwendeten Methoden sehr heterogen ist, ist das Ziel des ersten Beitrags dieser publikationsbasierten Dissertation, eine Anleitung für eine systematische Durchführung einer Äquivalenzuntersuchung, speziell für Large-Scale Assessments, zu geben. Dabei wird die exemplarisch dargelegte Modus-Effekt-Analyse anhand von zuvor definierten und in ihrer Bedeutsamkeit belegten Kriterien auf der Test- und Item-Ebene illustriert. Zudem wird die Möglichkeit beschrieben, auftretende Effekte anhand von Eigenschaften des Administrationsmodus’, beispielsweise des Antwortformats oder der Navigationsmöglichkeiten innerhalb des Tests, zu erklären. Im zweiten und dritten Beitrag findet sich jeweils eine empirische Anwendung der im ersten Beitrag beschriebenen schematischen Modus-Effekt-Analyse mit unterschiedlicher Schwerpunktsetzung. Dazu wurden die Daten eines Leseverständnistests aus der Nationalen Begleitforschung von PISA 2012 sowie zweier Leseverständnistests im NEPS, die jeweils sowohl papier- als auch computerbasiert administriert wurden, analysiert. Das Kriterium der Konstrukt-Äquivalenz steht dabei als wichtigstes Äquivalenz-Kriterium im Fokus. Zusätzlich wurde Äquivalenz in Bezug auf die Reliabilität und die Item-Parameter (Schwierigkeit und Diskrimination) untersucht. Im zweiten Beitrag wurden darüber hinaus interindividuelle Unterschiede im Modus-Effekt in Bezug zu basalen Computerfähigkeiten und zum Geschlecht gesetzt. Der dritte Beitrag fokussiert die Item-Eigenschaften, die als mögliche Quellen von Modus-Effekten herangezogen werden können und bezieht diese zur Erklärung von Modusunterschieden in die Analyse mit ein. In beiden Studien wurde keine Evidenz gefunden, dass sich das Konstrukt bei einem Wechsel des Administrationsmodus ändert. Lediglich einzelne Items wiesen am Computer im Vergleich zum PBA eine erhöhte Schwierigkeit auf, wobei sich der größte Teil der Items als invariant zwischen den Modi erwies. Für zwei Item-Eigenschaften wurde ein Effekt auf die erhöhte Schwierigkeit der Items am Computer gefunden. Interindividuelle Unterschiede im Modus-Effekt konnten nicht durch basale Computerfähigkeiten oder das Geschlecht erklärt werden.
Diese Dissertation leistet einen wesentlichen Beitrag zur Systematisierung von Äquivalenzuntersuchungen, insbesondere solchen in Large-Scale Assessments, indem sie die wesentlichen Kriterien für die Beurteilung von Äquivalenz herausstellt und diskutiert sowie deren Analyse methodisch aufbereitet. Die Relevanz von Modus-Effekt Studien wird dabei nicht zuletzt durch die Ergebnisse der beiden empirischen Beiträge hervorgehoben. Schließlich wird der Bedeutung des Einbezugs von Item-Eigenschaften hinsichtlich der Beurteilung der Äquivalenz Ausdruck verliehen.
In this study, we aimed to comparatively evaluate high-resolution 3D ultrasonography (hrUS), in-vivo micro-CT (μCT) and 9.4T MRI for the monitoring of tumor growth in an orthotopic renal cell carcinoma (RCC) xenograft model since there is a lack of validated, non-invasive imaging tools for this purpose. 1 × 106 Caki-2 RCC cells were implanted under the renal capsule of 16 immunodeficient mice. Local and systemic tumor growth were monitored by regular hrUS, μCT and MRI examinations. Cells engrafted in all mice and gave rise to exponentially growing, solid tumors. All imaging techniques allowed to detect orthotopic tumors and to precisely calculate their volumes. While tumors appeared homogenously radiolucent in μCT, hrUS and MRI allowed for a better visualization of intratumoral structures and surrounding soft tissue. Examination time was the shortest for hrUS, followed by μCT and MRI. Tumor volumes determined by hrUS, μCT and MRI showed a very good correlation with each other and with caliper measurements at autopsy. 10 animals developed pulmonary metastases being well detectable by μCT and MRI. In conclusion, each technique has specific strengths and weaknesses, so the one(s) best suitable for a specific experiment may be chosen individually.
The goal of heavy ion reactions at low beam energies is to explore the QCD phase diagram at high net baryon chemical potential. To relate experimental observations with a first order phase transition or a critical endpoint, dynamical approaches for the theoretical description have to be developed. In this summary of the corresponding plenary talk, the status of the dynamical modeling including the most recent advances is presented. The remaining challenges are highlighted and promising experimental measurements are pointed out.
We propose that resilience effectively helps people cope with stress, thus predominantly reducing the negative. However, we argue that individuals’ social identification has the potential to contribute to their well-being, thus fostering the positive. A two-wave survey study of 180 students shows that resilience is more strongly (negatively) associated with ill-health (i.e. stress and depression), whereas social identification is more strongly (positively) related to well-being (i.e. satisfaction and work engagement). We believe that it is necessary to see these two routes to improving people’s health as complementary, both in future research and for therapy and interventions.
Pediatric patients with recurrent, refractory or advanced soft tissue sarcoma (STS) who are simultaneously showing signs of cumulative treatment toxicity are in need of novel therapies. In this preclinical analysis, we identified ErbB2 as a targetable antigen on STS cells and used cytokine-induced killer (CIK) cells transduced with the lentiviral 2nd-generation chimeric antigen receptor (CAR) vector pS-5.28.z-IEW to target ErbB2-positive tumors. Solely CIK cell subsets with the CD3+ T cell phenotype showed up to 85% cell surface expression of the respective CAR. A comparison of wildtype (WT), mock-vector and ErbB2-CAR-CIK cells showed, that engineered cells exhibited diminished in vitro expansion, retained WT CIK cell phenotype with higher percentages of differentiated effector memory/effector cells. Activating natural killer (NK) cell receptor NKG2D-restricted target cell recognition and killing of WT and ErbB2-CAR-CIK cells was maintained against ErbB2-negative tumors, while ErbB2-CAR-CIK cells demonstrated significantly increased cytotoxicity against ErbB2-positive targets, including primary tumors. ErbB2-CAR- but not WT CIK cells proliferated, infiltrated and efficiently lysed tumor cell monolayers as well as 3D tumor spheroids.
Here, we demonstrate a potential cell therapeutic approach using ErbB2-CAR-CIK cells for the recognition and elimination of tumor cells expressing ErbB2, which we identified as a targetable antigen on high-risk STS cells.
Am Fachbereich Medizin und dem Klinikum der Johann Wolfgang-Goethe-Universität Frankfurt existierten bereits seit 2002 mehrere einzelne medizindidaktische Kurse. Diese Aktivitäten wurden 2011 strukturiert, ein umfassendes Kursangebot, das das breite Spektrum an Themen rund um die Lehre abdeckt, wurde aufgebaut und unter dem Dach der Frankfurter Arbeitsstelle für Medizindidaktik (FAM) am Fachbereich institutionalisiert. Folgende Faktoren waren für die erfolgreiche Umsetzung ausschlaggebend: vorhandene Programme in anderen Bundesländern (v.a. Baden-Württemberg, Nordrhein-Westfalen) mit entsprechenden Vorgaben, die Unterstützung der Studiendekane, die Verankerung der Teilnahme an medizindidaktischen Kursen in der Habilitationsordnung sowie eine kritische Masse von an der Lehre interessierten Mitarbeiterinnen und Mitarbeitern. Kernelemente des Angebots sind ein Basiskurs für alle neu eingestellten wissenschaftlichen Angestellten mit Lehrverpflichtung und ein modularer Aufbau des Programms, der individuellen Präferenzen bzw. Erfordernissen entgegen kommt. Gleichwohl die Teilnahme am Kursprogramm überwiegend verpflichtend erfolgt, zeigt sich eine hohe Zufriedenheit und ein nachhaltiger Wissenszuwachs bei den Kursteilnehmerinnen und Kursteilnehmern.
Sepsis is generally considered as a severe condition of inflammation that leads to lymphocyte apoptosis and multiple organ dysfunction. Hydroxysafflor yellow A (HSYA) exerts anti-inflammatory and anti-apoptotic effects in infectious diseases. However, the therapeutic effect of HSYA on polymicrobial sepsis remains unknown. This study was undertaken to investigate the therapeutic effects and the mechanisms of action of HSYA on immunosuppression in a murine model of sepsis induced by cecal ligation and puncture (CLP). NIH mice were randomly divided into four groups: control group, sham group, CLP group, and CLP+HSYA group. HSYA (120 mg/kg) was intravenously injected into experimental mice at 12 h before CLP, concurrent with CLP and 12 h after CLP. The levels of circulating inflammatory cytokines, the apoptosis of CD4+ and CD8+ T lymphocytes, and protein expression of cytochrome C (Cytc), Bax, Bcl-2, cleaved caspase-9, and cleaved caspase-3 were examined. Plasma levels of IL-6, IL-10 and TNF-alpha as well as the apoptosis of CD4+ T lymphocytes were increased compared with sham group. These changes were accompanied by increases of pro-apoptotic proteins including Cytc, Bax, cleaved caspase-9, and cleaved caspase-3 and decreases of anti-apoptotic protein Bcl-2 in CD4+ T lymphocytes from mice undergoing CLP. In contrast, we fail to observe significant effect of HSYA on the apoptosis of CD8+ T lymphocytes in CLP-treated group. Of note, HSYA treatment reversed all above changes observed in CD4+ T lymphocytes, and significantly increased the ratio of CD4+:CD8+ T lymphocytes in CLP-treated mice. In conclusion, HSYA was an effective therapeutic agent in ameliorating sepsis-induced apoptosis of CD4+ T lymphocytes probably through its anti-inflammatory and anti-apoptotic effects.
We present a method that enables the identification and analysis of conformational Markovian transition states from atomistic or coarse-grained molecular dynamics (MD) trajectories. Our algorithm is presented by using both analytical models and examples from MD simulations of the benchmark system helix-forming peptide Ala5, and of larger, biomedically important systems: the 15-lipoxygenase-2 enzyme (15-LOX-2), the epidermal growth factor receptor (EGFR) protein, and the Mga2 fungal transcription factor. The analysis of 15-LOX-2 uses data generated exclusively from biased umbrella sampling simulations carried out at the hybrid ab initio density functional theory (DFT) quantum mechanics/molecular mechanics (QM/MM) level of theory. In all cases, our method automatically identifies the corresponding transition states and metastable conformations in a variationally optimal way, with the input of a set of relevant coordinates, by accurately reproducing the intrinsic slowest relaxation rate of each system. Our approach offers a general yet easy-to-implement analysis method that provides unique insight into the molecular mechanism and the rare but crucial (i.e., rate-limiting) transition states occurring along conformational transition paths in complex dynamical systems such as molecular trajectories.
In 1905, the managing editor of the Jewish Encyclopedia, Isidore Singer (1859–1939), published an article in the journal Ost und West from a "bird’s eye perspective on the development of American Jewry in the last 250 years." In this historical overview, Singer eventually attested that Jewish scholarship in America had an "absolute dependency on the European motherland." This judgment was based on his disapproving view of the two American rabbinical seminaries that existed at that time. According to Singer, there were still no scholars at the Hebrew Union College (HUC) in Cincinnati of the "already American[-born] generation of Israel." In fact, Singer’s observation was appropriate because it applied to the Jewish Theological Seminary of America (JTSA) in New York as much as to the HUC.3 Despite the history of Jewish settlement in America, around 1900 there was still no native Jewish scholarship in America. The scene was dominated by scholars educated in Europe, who often came with broken English and a strict academic sense of mission. In 1903, Kaufmann Kohler (1843–1926), born in Bavaria and trained at German universities, was chosen as the president of HUC. And a year earlier, Solomon Schechter (1847–1915) had been called to the JTSA in New York as its new president. ...
We performed an intercomparison of river discharge regulated by dams under four meteorological forcings among five global hydrological models for a historical period by simulation. This is the first global multimodel intercomparison study on dam-regulated river flow. Although the simulations were conducted globally, the Missouri–Mississippi and Green–Colorado Rivers were chosen as case-study sites in this study. The hydrological models incorporate generic schemes of dam operation, not specific to a certain dam. We examined river discharge on a longitudinal section of river channels to investigate the effects of dams on simulated discharge, especially at the seasonal time scale. We found that the magnitude of dam regulation differed considerably among the hydrological models. The difference was attributable not only to dam operation schemes but also to the magnitude of simulated river discharge flowing into dams. That is, although a similar algorithm of dam operation schemes was incorporated in different hydrological models, the magnitude of dam regulation substantially differed among the models. Intermodel discrepancies tended to decrease toward the lower reaches of these river basins, which means model dependence is less significant toward lower reaches. These case-study results imply that, intermodel comparisons of river discharge should be made at different locations along the river's course to critically examine the performance of hydrological models because the performance can vary with the locations.
A dozen mRNAs are edited by multiple insertions and/or deletions of uridine residues in the mitochondrion of Trypanosoma brucei. Several protein complexes have been implicated in performing this type of RNA editing, including the mitochondrial RNA-binding complex 1 (MRB1). Two paralogous novel RNA-binding proteins, MRB8170 and MRB4160, are loosely associated with the core MRB1 complex. Their roles in RNA editing and effects on target mRNAs are so far not well understood. In this study, individual-nucleotide-resolution UV-cross-linking and affinity purification (iCLAP) revealed a preferential binding of both proteins to mitochondrial mRNAs, which was positively correlated with their extent of editing. Integrating additional in vivo and in vitro data, we propose that binding of MRB8170 and/or MRB4160 onto pre-mRNA marks it for the initiation of editing and that initial binding of both proteins may facilitate the recruitment of other components of the RNA editing/processing machinery to ensure efficient editing. Surprisingly, MRB8170 also binds never-edited mRNAs, suggesting that at least this paralog has an additional role outside RNA editing to shape the mitochondrial transcriptome.
The existence of individual variation in males' motivation to mate remains a conundrum as directional selection should favour high mating frequencies. Balancing selection resulting from (context-dependent) female mate choice could contribute to the maintenance of this behavioural polymorphism. In dichotomous choice tests, mosquitofish (Gambusia holbrooki) females preferred virtual males showing intermediate mating frequencies, reflecting females' tendencies to avoid harassment by highly sexually active males. When tested in the presence of a female shoal—which protects females from male harassment—focal females showed significantly stronger preferences for high sexual activity. A trade-off between (indirect) benefits and (direct) costs of mating with sexually active males probably explains context-dependent female mate choice, as costs depend on the social environment in which females choose their mates. No preference was observed when we tested virgin females, suggesting that the behavioural pattern described here is part of the learned behavioural repertoire of G. holbrooki females.
Empirical evidence suggests that investments in research and development (R&D) by older and larger firms are more spread out internationally than R&D investments by younger and smaller firms. In this paper, I explore the quantitative implications of this type of heterogeneity by assuming that incumbents, i.e. current monopolists engaging in incremental innovation, have a higher degree of internationalization in their R&D technologies than entrants, i.e. new firms engaging in radical innovation, in a two-country endogenous growth general equilibrium model. In particular, this assumption allows the model to break the perfect correlation between incumbents’ and entrants’ innovation probabilities and to match the empirical counterpart exactly.
Vor einem Monat haben sich mehr als zwei Millionen Katalanen für die Unabhängigkeit der Region von Spanien ausgesprochen. Auch wenn das Referendum für illegal erklärt wurde und weniger als die Hälfte der Katalanen teilnahmen, verraten uns die Ergebnisse einiges über die Stärke der Unabhängigkeitsbewegung. Dieser Beitrag untersucht, wie ein mögliches legales Referendum mit höherer Wahlbeteiligung ausgehen könnte. Auch wenn die rechtlichen Rahmenbedingungen ein solches Referendum nicht vorsehen, unterstützen laut aktueller Umfragen auch eine Mehrheit der Spanier diesen Weg der Konfliktlösung.
What processes transform (im)mobile individuals into ‘migrants’ and geographic movements across political-territorial borders into ‘migration’? To address this question, the article develops the doing migration approach, which combines perspectives from social constructivism, praxeology and the sociologies of knowledge and culture. ‘Doing migration’ starts with the processes of social attribution that differentiate between ‘migrants’ and ‘non-migrants’. Embedded in institutional, organizational and interactional routines these attributions generate unique social orders of migration. By illustrating these conceptual ideas, the article provides insights into the elements of the contemporary European order of ‘migration’. Its institutional routines contribute to the emergence of a European migration regime that involves narratives of economization, securitization and humanitarization. The organizational routines of the European migration order involve surveillance and diversity management, which have disciplining effects on those defined as ‘migrants’. The routines of everyday face-to-face interactions produce various micro-forms of doing ‘migration’ through stigmatization and othering, but they also provide opportunities to resist a social attribution as ‘migrant’.
This paper reviews social network analysis (SNA) as a method to be utilized in biographical research which is a novel contribution. We argue that applying SNA in the context of biography research through standardized data collection as well as visualization of networks can open up participants’ interpretations of relations throughout their lives, and allow a creative and innovative way of data collection that is responsive to participants’ own meanings and associations while allowing the researchers to conduct systematical data analysis. The paper discusses the analytical potential of SNA in biographical research, where the efficacy of this method is critically discussed, together with its limitations, and its potential within the context of biographical research.
Wassergefiltertes Infrarot A (wIRA) ist eine spezielle Form der Wärmestrahlung mit hohem Eindringvermögen in das Gewebe und geringer thermischer Belastung der Hautoberfläche.
wIRA steigert deutlich Temperatur, Sauerstoffpartialdruck und Durchblutung im Gewebe und wirkt auch über nicht-thermische zelluläre Effekte.
wIRA mindert indikationsübergreifend Schmerzen (mit relevant weniger Analgetikabedarf), Entzündung und vermehrte Sekretion und fördert Infektionsabwehr und Regeneration.
Entsprechend breit sind die klinischen Anwendungsmöglichkeiten von wIRA.
wIRA ist ein kontaktfreies, verbrauchsmaterialfreies, leicht anzuwendendes, (selbst bei Wunden) als angenehm empfundenes Verfahren mit guter Tiefenwirkung und anhaltendem Wärmedepot.
wIRA ist u.a. einsetzbar zur Verbesserung der Heilung akuter und chronischer Wunden (wobei selbst eine ungestört "normal" ablaufende Wundheilung noch verbessert werden kann: schneller, schmerzärmer), bei Hauterkrankungen (wie vulgären Warzen, Herpes labialis, Herpes Zoster, Sklerodermie, Akne papulopustulosa; aktinischen Keratosen im Rahmen einer Photodynamischen Therapie), zur Resorptionsverbesserung topisch applizierter Substanzen, bei muskuloskeletalen Erkrankungen (wie Arthrosen, Arthritiden, Lumbago, ankylosierender Spondyloarthritis), zur Regeneration nach Sport, beim komplexen regionalen Schmerzsyndrom (CRPS), bei Polyneuropathien und in Kombination mit Strahlentherapie oder Chemotherapie in der Onkologie.
Case description: A patient with a Barrett oesophageal carcinoma and a resection of the oesophagus with gastric pull-up developed swallowing disorders 6 years and 2 months after the operation. Within 1 year and 7 months two recurrences of the tumor at the anastomosis were found and treated with combined chemoradiotherapy or chemotherapy respectively. 7 years and 9 months after the operation local tumor masses and destruction were present with no ability to orally drink or eat (full feeding by jejunal PEG tube): quality of life was poor, as saliva and mucus were very viscous (pulling filaments) and could not be swallowed and had to be spat out throughout the day and night resulting in short periods of sleep (awaking from the necessity to spit out). In total the situation was interpreted more as a problem related to a feeling of choking (with food or fluid) in the sense of a functional dysphagia rather than as a swallowing disorder from a structural stenosis.
At that time acetylcysteine (2 times 200 mg per day, given via the PEG tube) and irradiation with water-filtered infrared-A (wIRA), a special form of heat radiation, of the ventral part of the neck and the thorax were added to the therapy. Within 1 day with acetylcysteine saliva and mucus became less viscous. Within 2 days with wIRA (one day with 4 to 5 hours with irradiation with wIRA at home) salivation decreased markedly and quality of life clearly improved: For the first time the patient slept without interruption and without the need for sleep-inducing medication. After 5 days with wIRA the patient could eat his first soft dumpling although drinking of fluids was still not possible. After 2½ weeks with wIRA the patient could eat his first minced schnitzel (escalope).
Following the commencement of wIRA (with typically approximately 90–150 minutes irradiation with wIRA per day) the patient had 8 months with good quality of life with only small amounts of liquid saliva and mucus and without the necessity to spit out. During this period the patient was able to sleep during the night.
Discussion: The main physiological effects of water-filtered infrared-A (wIRA) are: wIRA increases tissue temperature, tissue oxygen partial pressure and tissue perfusion markedly.
The five main clinical effects of wIRA are: wIRA decreases pain, inflammation and exudation/hypersecretion, and promotes infection defense and regeneration, all in a cross-indication manner. Therefore there is a wide range of indications for wIRA.
The effects of wIRA are based on both its thermal effects (relying on transfer of heat energy) and thermic effects (temperature-dependent effects, occurring together with temperature changes) as well as on non-thermal and temperature-independent effects like direct effects on cells, cell structures or cell substances.
Conclusion: Besides in a variety of other indications for wIRA, in cases of swallowing disorders (functional dysphagia) and hypersalivation or hypersecretion of mucus the use of wIRA should be considered as part of the treatment regime for improving a patient’s quality of life.
Diese kulturanthropologische Studie beschäftigt sich mit gegenwärtigen Veränderungen des Nachkriegsphänomens Städtepartnerschaften. Ausgangspunkt ist die Beobachtung, dass, obwohl einstige Gründungsmotive wegfallen, Städtepartnerschaften derzeit nicht etwa abgeschafft oder ersetzt, sondern neu ausgerichtet werden. Im Zentrum der Arbeit steht daher die Frage nach den Charakteristiken des gegenwärtigen Wandels und der kulturellen Spezifik von Städtepartnerschaften sowie möglichen Folgen. Dem wird am Beispiel von deutsch-polnischen und deutsch-türkischen Städtepartnerschaften des Ruhrgebiets mit Methoden einer transnational ausgerichteten empirisch-ethnografischen Feldforschung und einer akteurszentrierten und praxisorientierten Anwendung des Assemblage-Konzepts nachgegangen. Die Ergebnisse, die sich schwerpunktmäßig auf einen Zeitraum zwischen 2007 und 2012 beziehen, machen nicht zuletzt durch ihren länderbezogenen Kontrast deutlich: In Städtepartnerschaften trifft derzeit eine Vielzahl von aktuellen Entwicklungen, Prozessen und Akteuren aufeinander. Städtepartnerschaften werden derzeit staatsgrenzenübergreifend von verschiedenen Akteuren aus Politik, Zivilgesellschaft und Bürgerschaft mit je eigenen derzeitigen Herausforderungen wie Integrationsfragen und Wirtschaftsförderung, urbanem Standortwettbewerb sowie biografischen Bestrebungen und Mobilitätsinteressen verbunden. Dabei führen insbesondere auf deutscher Seite normative Ansprüche dazu, dass einstige Prinzipien und Aktivitäten von Städtepartnerschaften beibehalten und abgewandelt werden, weshalb von einem Format und einem Formatwandel gesprochen werden kann, was nicht jede beliebige Veränderung zulässt. In den neueren Varianten von Städtepartnerschaften zeigen sich aber auch nicht zwangsläufig intendierte, doch sehr wirkungsvolle Formen von Europäisierung und Governance durch Kommunen und ihre Bürgerinnen und Bürger.
Walter Greiner: in memoriam
(2017)
Walter Greiner (29 October 1935 - 6 October 2016) was a German theoretical physicist. His scientific research interests include the thematic areas of atomic physics, heavy ion physics, nuclear physics, elementary particle physics (particularly quantum electrodynamics and quantum chromodynamics). He is most known in Germany for his series of books in theoretical physics, but he is also well known around the world. Greiner was born on October 29, 1935, in Neuenbau, Sonnenberg, Germany. He studied physics at the University of Frankfurt (Goethe University in Frankfurt Am Main), receiving in this institution a BSci in physics and a Master’s degree in 1960 with a thesis on plasma-reactors, and a PhD in 1961 at the University of Freiburg under Hans Marshal, with a thesis on the nuclear polarization in μμ-mesic atoms. During the period of 1962 to 1964 he was assistant professor at the University of Maryland, followed by a position as research associate at the University of Freiburg, in 1964. Starting in 1965, he became a full professor at the Institute for Theoretical Physics at Goethe University until 2003. Greiner has been a visiting professor to many universities and laboratories, including Florida State University, the University of Virginia, the University of California, the University of Melbourne, Vanderbilt University, Yale University, Oak Ridge National Laboratory and Los Alamos National Laboratory. In 2003, with Wolf Singer, he was the founding Director of the Frankfurt Institute for Advanced Studies (FIAS), and gave lectures and seminars in elementary particle physics. He died on October 6, 2016 at the age of 80.
Walter Greiner was an excellent teacher, researcher, friend. And he was a great supporter of the series of events known by the acronyms IWARA - International Workshop on Astronomy and Relativistic Astrophysics, STARS - Caribbean Symposium on Cosmology, Gravitation, Nuclear and Astroparticle Physics, and SMFNS - International Symposium on Strong Electromagnetic Fields and Neutron Stars. Walter Greiner left us. But his memory will remain always alive among us who have had the privilege of knowing him and enjoy his wisdom and joy of living.
Land surface and hydrologic models (LSM/HM) are used at diverse spatial resolutions ranging from 1-10 km in catchment-scale applications to over 50 km in global-scale applications. Application of the same model structure at different spatial scales requires that the model estimates similar fluxes independent of the model resolution and fulfills a flux-matching condition across scales. An analysis of state-of-the-art LSMs and HMs reveals that most do not have consistent and realistic parameter fields for land surface geophysical properties. Multiple experiments with the mHM, Noah-MP, PCR-GLOBWB and WaterGAP models are conducted to demonstrate the pitfalls of poor parameterization practices currently used in most operational models, which are insufficient to satisfy the flux-matching condition. These examples demonstrate that J. Dooge’s 1982 statement on the unsolved problem of parameterization in these models remains true. We provide a short review of existing parameter regionalization techniques and discuss a method for obtaining seamless hydrological predictions of water fluxes and states across multiple spatial resolutions. The multiscale parameter regionalization (MPR) technique is a practical and robust method that provides consistent (seamless) parameter and flux fields across scales. A general model protocol is presented to describe how MPR can be applied to a specific model, with an example of this application using the PCR-GLOBWB model. Applying MPR to PCR-GLOBWB substantially improves the flux-matching condition. Estimation of evapotranspiration without MPR at 5 arcmin and 30 arcmin spatial resolutions for the Rhine river basin results in a difference of approximately 29%. Applying MPR reduce this difference to 9%. For total soil water, the differences without and with MPR are 25% and 7%, respectively.
Land surface and hydrologic models (LSMs/HMs) are used at diverse spatial resolutions ranging from catchment-scale (1–10 km) to global-scale (over 50 km) applications. Applying the same model structure at different spatial scales requires that the model estimates similar fluxes independent of the chosen resolution, i.e., fulfills a flux-matching condition across scales. An analysis of state-of-the-art LSMs and HMs reveals that most do not have consistent hydrologic parameter fields. Multiple experiments with the mHM, Noah-MP, PCR-GLOBWB, and WaterGAP models demonstrate the pitfalls of deficient parameterization practices currently used in most operational models, which are insufficient to satisfy the flux-matching condition. These examples demonstrate that J. Dooge's 1982 statement on the unsolved problem of parameterization in these models remains true. Based on a review of existing parameter regionalization techniques, we postulate that the multiscale parameter regionalization (MPR) technique offers a practical and robust method that provides consistent (seamless) parameter and flux fields across scales. Herein, we develop a general model protocol to describe how MPR can be applied to a particular model and present an example application using the PCR-GLOBWB model. Finally, we discuss potential advantages and limitations of MPR in obtaining the seamless prediction of hydrological fluxes and states across spatial scales.
A randomised, double-blind, placebo-controlled trial of trichuris suis ova in active crohn's disease
(2017)
BACKGROUND AND AIMS To investigate the efficacy and safety of three different dosages of embryonated, viable eggs of Trichuris suis [TSO] versus placebo for induction of remission in mildly-to-moderately active ileocolonic, uncomplicated Crohn's disease [CD].
METHODS Adults with active CD [n = 252] randomly received six fortnightly doses of 250, 2500, or 7500 TSO/15 ml suspension/day [TSO 250, TSO 2500, TSO 7500], or 15 ml placebo solution/day, in a double-blind fashion, with 4 weeks' follow-up. Primary endpoint was the rate of clinical remission [Crohn's Disease Activity Index [CDAI] < 150] at end of treatment, ie at Week 12 or withdrawal. Secondary endpoints included the course of clinical remission, rate of clinical response, change in CDAI, change in markers of inflammation, mucosal healing, and Physician's Global Assessment.
RESULTS Clinical remission at Week 12 occurred in 38.5%, 35.2%, and 47.2% of TSO 250, TSO 2500, and TSO 7500 patients, respectively, and in 42.9% of placebo recipients. TSO induced a dose-dependent immunological response. There was no response regarding laboratory markers of inflammation. Other secondary efficacy variables also showed no advantage of TSO over placebo for treatment of active CD. Administration of TSO did not result in any serious adverse drug reaction. Review of non-serious suspected adverse drug reactions following TSO did not reveal any safety concerns.
CONCLUSIONS Administration of 250-7500 TSO fortnightly over 12 weeks was safe and showed a dose-dependent immunological response, but no TSO dose showed a clinically relevant effect over placebo for induction of clinical remission or response in mildly-to-moderately active, ileocolonic CD.
Kinematic analysis of work-related musculoskeletal loading of trunk among dentists in Germany
(2017)
BACKGROUND: In Germany, about 86.7 % of the dentists have stated to suffer from pain in the neck and shoulder region. These findings are predominantly based on surveys. Therefore the objective of this study is to conduct a kinematic analysis of occupational posture in dentistry.
METHODS: Twenty one dentists (11 f/10 m; age: 40.1 ± 10.4 years) have participated in this examination. The CUELA-System was used to collect kinematic data of the activities on an average dental workday. A detailed, computer-based task analysis took place parallel to the kinematic examination. Through the synchronization of data collected from both measurements, patterns of posture were arranged chronologically and in conjunction with the tasks performed: (I) "treatment" (II) "office" and (III) "other activities". For the data analysis, characteristic data of joint angular distributions (percentiles P05, P25, P50, P75 and P95) of head, neck and torso at pre-defined tasks were examined and assessed corresponding to ergonomic standards.
RESULTS: Forty one percent of tasks executed on an average dental workday can be categorized as the treatment of patients. These tasked are most frequently performed in "straight back" positions (78.7 %), whereas 20.1 % were carried out in a "twisted or inclined" torso posture, 1.1 % "bowed" and only 0.1 % "bowed and twisted/inclined to the side" upper body position. In particular, it can be observed that in the area of the cervical and thoracic spine the 75th and 95th percentile show worse angular values during treatment than during non-dental tasks. For the period of treatment (at a standardized dental chair construction), a seated position with a strong inclination of the thoracic spine to the right while the lumbar spine is inclined towards the left is adopted.
CONCLUSION: The kinematic analysis of dentists illustrates typical patterns of postures during tasks that are essential to the dental treatment of patients. The postures in the area of the cervical and thoracic spine have higher angular values during treatment compared to other dental tasks. Consistently, appropriate ergonomic design measures to optimize the dental chair and equipment as well as integrated training in ergonomics as part of the study of dentistry to prevent musculoskeletal are recommended.
A precise definition of a brain state has proven elusive. Here, we introduce the novel local-global concept of intrinsic ignition characterizing the dynamical complexity of different brain states. Naturally occurring intrinsic ignition events reflect the capability of a given brain area to propagate neuronal activity to other regions, giving rise to different levels of integration. The ignitory capability of brain regions is computed by the elicited level of integration for each intrinsic ignition event in each brain region, averaged over all events. This intrinsic ignition method is shown to clearly distinguish human neuroimaging data of two fundamental brain states (wakefulness and deep sleep). Importantly, whole-brain computational modelling of this data shows that at the optimal working point is found where there is maximal variability of the intrinsic ignition across brain regions. Thus, combining whole brain models with intrinsic ignition can provide novel insights into underlying mechanisms of brain states.
The signal transducer and activator of transcription 5 (STAT5) regulates differentiation, survival, proliferation and transformation of hematopoietic cells. Upon cytokine stimulation, STAT5 tyrosine phosphorylation (pYSTAT5) is transient, while in diverse neoplastic cells persistent overexpression and enhanced pYSTAT5 are frequently found. Post-translational modifications might contribute to enhanced STAT5 activation in the context of transformation, but the strength and duration of pYSTAT5 are incompletely understood. We found that O-GlcNAcylation and tyrosine phosphorylation act together to trigger pYSTAT5 levels and oncogenic transcription in neoplastic cells. The expression of a mutated hyperactive gain-of-function (GOF) STAT5 without O-GlcNAcylation resulted in decreased tyrosine phosphorylation, oligomerization and transactivation potential and complete loss of oncogenic transformation capacity. The lack of O-GlcNAcylation diminished phospho-ERK and phospho-AKT levels. Our data show that O-GlcNAcylation of STAT5 is an important process that contributes to oncogenic transcription through enhanced STAT5 tyrosine phosphorylation and oligomerization driving myeloid transformation. O-GlcNAcylation of STAT5 could be required for nutrient sensing and metabolism of cancer cells.