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Einleitung
(2020)
Seit Wochen nun beobachten wir, wie Menschen auf sehr unterschiedliche Weise auf die COVID-19-Pandemie reagieren. Die unmittelbare Gefahrenursache ist zwar für das bloße Auge nicht sichtbar. Sichtbar hingegen sind die von der Weltgesundheitsorganisation, der Johns Hopkins Universität oder dem Robert-Koch-Institut veröffentlichten Daten. Täglich steigende Zahlen von Infizierten, täglich steigende Zahlen von Toten. Vielleicht ist es nachvollziehbar, dass "in diesen Zeiten" Regelungsmaßnahmen "mit heißer Nadel gestrickt" (noch so eine Phrase) sind. Selbst wenn in der Theorie Krisenszenarien vielleicht irgendwann einmal durchgespielt worden sind (siehe BT Drs. 17/12051, S. 57 ff.), lässt sich nicht jede Variante einer Krise antizipieren – genauso wenig wie der tatsächliche Stressmodus, in dem andere und man selbst sich befinden werden. In diesem Modus sind nun Entscheidungen getroffen worden. Entscheidungen, deren Konsequenzen ohne jegliche Übertreibung als der "massivste kollektive Grundrechtseingriff in der Geschichte der Bundesrepublik" bezeichnet werden können. ...
Background: Data on Candida bloodstream infections in pediatric patients in Europe are limited. We performed a retrospective multicenter European study of the epidemiology and outcome of neonatal and pediatric candidemia.
Material and Methods: All first positive blood cultures from patients ≤ 18 years of age with candidemia were registered. Patients’ demographic and clinical characteristics and causative Candida species were collected and analyzed. Regression analysis was used to identify factors independently associated with mortality.
Results: One thousand three hundred ninety-five episodes of candidemia (57.8% male) were reported from 23 hospitals in 10 European countries. Of the 1395 episodes, 36.4% occurred in neonates (≤ 44 weeks postmenstrual age), 13.8% in infants (> 44 weeks postmenstrual age to 1 year) and 49.8% in children and adolescents. Candida albicans (52.5%) and Candida parapsilosis (28%) were the predominant species. A higher proportion of candidemia caused by C. albicans was observed among neonatal patients (60.2%) with highest rates of C. parapsilosis seen among infants (42%). Children admitted to hematology-oncology wards presented the highest rates of non-albicans Candida species. Candidemia because of C. albicans was more frequent than non-albicans Candida in Northern versus Southern Europe (odds ratio, 2.3; 95% confidence interval, 1.8–2.9; P < 0.001). The all-cause mortality at 30 days was 14.4%. All-cause mortality was higher among patients admitted to the neonatal or pediatric intensive care units than other wards. Over time, no significant changes in species distribution were observed.
Conclusions: This first multicenter European study shows unique characteristics of the epidemiology of pediatric candidemia. The insights obtained from this study will be useful to guide clinical management and antifungal stewardship.
Non-random connectivity can emerge without structured external input driven by activity-dependent mechanisms of synaptic plasticity based on precise spiking patterns. Here we analyze the emergence of global structures in recurrent networks based on a triplet model of spike timing dependent plasticity (STDP) which depends on the interactions of three precisely-timed spikes and can describe plasticity experiments with varying spike frequency better than the classical pair-based STDP rule. We derive synaptic changes arising from correlations up to third-order and describe them as the sum of structural motifs which determine how any spike in the network influences a given synaptic connection through possible connectivity paths. This motif expansion framework reveals novel structural motifs under the triplet STDP rule, which support the formation of bidirectional connections and ultimately the spontaneous emergence of global network structure in the form of self-connected groups of neurons, or assemblies. We propose that under triplet STDP assembly structure can emerge without the need for externally patterned inputs or assuming a symmetric pair-based STDP rule common in previous studies. The emergence of non-random network structure under triplet STDP occurs through internally-generated higher-order correlations, which are ubiquitous in natural stimuli and neuronal spiking activity, and important for coding. We further demonstrate how neuromodulatory mechanisms that modulate the shape of the triplet STDP rule or the synaptic transmission function differentially promote structural motifs underlying the emergence of assemblies, and quantify the differences using graph theoretic measures.
In a 40-year-old caucasian patient with stress incontinence was a TVT operation performed with an autologous semitendinosus tendon transplant. The operation was done with spinal anesthesia. The tendon of the right musculus semitendinosus was stripped from the popliteal fossa and used instead of a synthetic tape as midurethral sling, as it is done in a classical retropubic TVT procedure. The operation was performed successfully. On the first day after the operation the transurethral catheter was removed, continence was reached, and no urinary retention was seen. Mobility and power of the affected leg did not change.
Background: The back pain screening tool Risk-Prevention-Index Social (RPI-S) identifies the individual psychosocial risk for low back pain chronification and supports the allocation of patients at risk in additional multidisciplinary treatments. The study objectives were to evaluate (1) the prognostic validity of the RPI-S for a 6-month time frame and (2) the clinical benefit of the RPI-S. Methods: In a multicenter single-blind 3-armed randomized controlled trial, n = 660 persons (age 18-65 years) were randomly assigned to a twelve-week uni- or multidisciplinary exercise intervention or control group. Psychosocial risk was assessed by the RPI-S domain social environment (RPI-SSE) and the outcome pain by the Chronic Pain Grade Questionnaire (baseline M1, 12-weeks M4, 24-weeks M5). Prognostic validity was quantified by the root mean squared error (RMSE) within the control group. The clinical benefit of RPI-SSE was calculated by repeated measures ANOVA in intervention groups. Results: A subsample of n = 274 participants (mean = 38.0 years, SD 13.1) was analyzed, of which 30% were classified at risk in their psychosocial profile. The half-year prognostic validity was good (RMSE for disability of 9.04 at M4 and of 9.73 at M5; RMSE for pain intensity of 12.45 at M4 and of 14.49 at M5). People at risk showed significantly stronger reduction in pain disability and intensity at M4/M5, if participating in a multidisciplinary exercise treatment. Subjects at no risk showed a smaller reduction in pain disability in both interventions and no group differences for pain intensity. Regarding disability due to pain, around 41% of the sample would gain an unfitted treatment without the back pain screening. Conclusion: The RPI-SSE prognostic validity demonstrated good applicability and a clinical benefit confirmed by a clear advantage of an individualized treatment possibility.
The Specialised Information Service Performing Arts (SIS PA) is part of a funding programme by the German Research Foundation that enables libraries to develop tailor-made services for individual disciplines in order to provide researchers direct access to relevant materials and resources from their field. For the field of performing arts, the SIS PA is aggregating metadata about theater and dance resources from currently, mostly, German-speaking cultural heritage institutions in a VuFind-based search portal.
In this article, we focus on metadata quality and its impact on the aggregation workflow by describing the different, possibly data provider-specific, process stages of improving data quality in order to achieve a searchable, interlinked knowledge base. We also describe lessons learned and limitations of the process.
Bevor der Bundesgesundheitsminister mit der Corona-Bewältigung in das Rampenlicht der Öffentlichkeit treten konnte, versuchte er in einer Reihe von Gesetzgebungsvorhaben und Maßnahmen, die deutsche gesetzliche Krankenversicherung (GKV) zu verändern. Eine seiner Maßnahmen war das Digitale-Versorgung-Gesetz, das der Bundestag im Dezember 2019 verabschiedete (DVG, BGBl. I, S. 2562) und die medizinische Versorgung durch Digitalisierung und Innovation verbessern sollte. Es sieht u.a. vor, Gesundheits-Apps auf Rezept zu verschreiben und Videosprechstunden und Telemedizin zum Alltag werden zu lassen. Vor allem aber sollen umfangreiche medizinische Daten der Versicherten in einem Forschungsdatenzentrum zusammengeführt und effektiv ausgewertet werden, um bessere Erkenntnisse in der Gesundheitsforschung zu erlangen.
Dagegen hatte ein Versicherter Beschwerde erhoben, und das Bundesverfassungsgericht hat im Verfahren des einstweiligen Rechtsschutzes entschieden, dass Teile dieses Gesetzes – nämlich §§ 68a Abs. 5 und 303a-303f SGB V – in der Tat erhebliche verfassungsrechtliche Bedenken aufwerfen. Dennoch hat das Gericht den Vollzug dieser Regelungen nicht ausgesetzt (Rn. 6 ff.) und noch nicht einmal die hilfsweise beantragte Reduktion des Datenumgangs angeordnet. Das ist im Ergebnis, vor allem aber in seiner Begründung unter mindestens zwei Aspekten kritisch zu betrachten.
Datenschutz versus Katastrophenschutz : Standortdaten als Mittel zur Bekämpfung der Corona-Pandemie
(2020)
Einige Länder setzen Standortdaten jetzt schon gezielt ein, um die weitere Ausbreitung von Covid-19 einzudämmen. Ein Gesetzentwurf von Bundesgesundheitsminister Jens Spahn, der weitreichende Befugnisse vorsah, um mithilfe von Standortdaten Kontaktpersonen von Infizierten über deren Handys zu orten, stieß auf teilweise heftige Kritik. Der Gesetzentwurf wurde daraufhin zurückgezogen, ohne dass nähere Einzelheiten an die Öffentlichkeit gelangt sind. Ein genauer Blick zeigt jedoch, dass eine Verarbeitung von Standortgesundheitsdaten nicht nur tatsächlich nützlich sein kann, sondern auch rechtlich möglich ist.
The Goethe University Frankfurt has updated its APC expenditures, providing data for the 2019 period.
The University Library Johann Christian Senckenberg is in charge of the University’s Open Access Publishing Fund, which is supported under the DFG’s Open Access Publishing Programme.
Contact Person is Roland Wagner.
This paper summarizes key elements of the German Federal Constitutional Court’s decision on the European Central Bank’s Public Sector Asset Purchase Programme. It briefly explains how it is possible for the German Court to disagree with the ruling of the Court of Justice of the European Union. Finally, it makes suggestions concerning a practical way forward for the Governing Council of the ECB in light of these developments.
Diamond formation in the Earth has been extensively discussed in recent years on the basis of geochemical analysis of natural materials, high-pressure experimental studies, or theoretical aspects. Here, we demonstrate experimentally for the first time, the spontaneous crystallization of diamond from CH4-rich fluids at pressure, temperature and redox conditions approximating those of the deeper parts of the cratonic lithospheric mantle (5-7 GPa) without using diamond seed crystals or carbides. In these experiments the fluid phase is nearly pure methane, even though the oxygen fugacity was significantly above metal saturation. We propose several previously unidentified mechanisms that may promote diamond formation under such conditions and which may also have implications for the origin of sublithospheric diamonds. These include the hydroxylation of silicate minerals like olivine and pyroxene, H2 incorporation into these phases and the "etching" of graphite by H2 and CH4 and reprecipitation as diamond. This study also serves as a demonstration of our new high-pressure experimental technique for obtaining reduced fluids, which is not only relevant for diamond synthesis, but also for investigating the metasomatic origins of diamond in the upper mantle, which has further implications for the deep carbon cycle.
Hintergrund: Die chronische metabolischen Azidose (cmA) ist eine häufige Komplikation bei chronischer Niereninsuffizienz, deren Behandlung bei niereninsuffizienten Patienten mit Diabetes mellitus die Insulinresistenz verbessern kann. Um die aktuelle Therapiesituation der cmA im diabetologischen Umfeld abzubilden und mehr über die Zusammenarbeit von Diabetologen und Nephrologen zu erfahren, wurden diabetologisch tätige Haus- und Fachärzte zur cmA befragt.
Methoden An 5863 Ärzten mit diabetologischer Zusatzqualifikation wurde postalisch ein Fragebogen versandt. Alle 97 erhaltenen Antwortbögen wurden deskriptiv ausgewertet.
Ergebnisse Die meisten Teilnehmer sind Internisten mit diabetologischer Zusatzqualifikation (46 %) und behandeln im Median 50 (10; 112) Patienten mit Typ-1-Diabetes bzw. 210 (100; 450) Patienten mit Typ-2-Diabetes pro Quartal. Eine cmA wurde von 12 % der Teilnehmer in den letzten 12 Monaten bei median 4 (2; 6) Patienten mit Typ-1-Diabetes und 10 (3; 30) Patienten mit Typ-2-Diabetes beobachtet. Die cmA wird überwiegend durch Bestimmung des Serum-Bikarbonats (27; 28 %) und des Base Excess (19; 20 %) diagnostiziert. 38 (39 %) der Teilnehmer erhalten regelmäßig von Nephrologen die Empfehlung zur Behandlung der cmA. Sie wird von knapp 1 Drittel als relevant (29 %) und gut umsetzbar (27 %) betrachtet. Zur Behandlung der cmA wird vor allem orales Bikarbonat empfohlen (Bikarbonat: 39 %, Zitrat: 5 %, sonst: keine Angabe). Maßnahmen, die die Mehrheit der Diabetologen in der Verantwortung der Nephrologen sehen, sind ergänzende Diagnostik (87; 90 %) einschließlich Blutgasanalyse (59 %) sowie die Behandlung der cmA (62 %) und renalen Anämie (53 %). 34 % der Diabetologen gaben an, bisher noch keine cmA-Fälle in der Praxis behandelt zu haben. Die meisten Diabetologen überlassen die Behandlung und Überwachung der cmA dem Nephrologen (38 %). Dabei wird die Zusammenarbeit mit den Nephrologen als zufriedenstellend (81 %) bewertet. 38 % der Befragten haben in der täglichen Praxis beobachtet, dass die Einstellung der cmA auch die Insulinresistenz positiv beeinflusst. Eine CME-Fortbildung in der Diabetologie speziell zur cmA würden 76 (78 %) begrüßen.
Diskussion Bei der Behandlung der cmA wird die Kooperation zwischen Diabetologen und Nephrologen generell gut bewertet, wobei die Diagnose, Behandlung und Überwachung einer cmA in der Verantwortung des Nephrologen gesehen werden. Da die Behandlung der cmA die Insulinresistenz verringern kann, sollte der Stellenwert der cmA-Therapie im diabetologischen Umfeld nicht unterschätzt werden. Um die cmA-Behandlung bei diabetischer Nephropathie zu optimieren, wären CME-Fortbildungen zur cmA geeignet. Zudem könnten Schulungen im Rahmen einer interdisziplinären Kooperation mit Diätberatern die Umsetzbarkeit diätetischer Interventionen zur Behandlung der cmA verbessern.
Background & Aims: Spontaneous portosystemic shunts (SPSS) frequently develop in liver cirrhosis. Recent data suggested that the presence of a single large SPSS is associated with complications, especially overt hepatic encephalopathy (oHE). However, the presence of >1 SPSS is common. This study evaluates the impact of total cross-sectional SPSS area (TSA) on outcomes in patients with liver cirrhosis.
Methods: In this retrospective international multicentric study, CT scans of 908 cirrhotic patients with SPSS were evaluated for TSA. Clinical and laboratory data were recorded. Each detected SPSS radius was measured and TSA calculated. One-year survival was the primary endpoint and acute decompensation (oHE, variceal bleeding, ascites) was the secondary endpoint.
Results: A total of 301 patients (169 male) were included in the training cohort. Thirty percent of all patients presented with >1 SPSS. A TSA cut-off of 83 mm2 was used to classify patients with small or large TSA (S-/L-TSA). Patients with L-TSA presented with higher model for end-stage liver disease score (11 vs. 14) and more commonly had a history of oHE (12% vs. 21%, p <0.05). During follow-up, patients with L-TSA experienced more oHE episodes (33% vs. 47%, p <0.05) and had lower 1-year survival than those with S-TSA (84% vs. 69%, p <0.001). Multivariate analysis identified L-TSA (hazard ratio 1.66; 95% CI 1.02–2.70, p <0.05) as an independent predictor of mortality. An independent multicentric validation cohort of 607 patients confirmed that patients with L-TSA had lower 1-year survival (77% vs. 64%, p <0.001) and more oHE development (35% vs. 49%, p <0.001) than those with S-TSA.
Conclusion: This study suggests that TSA >83 mm2 increases the risk for oHE and mortality in patients with cirrhosis. Our results support the clinical use of TSA/SPSS for risk stratification and decision-making in the management of patients with cirrhosis.
Lay summary: The prevalence of spontaneous portosystemic shunts (SPSS) is higher in patients with more advanced chronic liver disease. The presence of more than 1 SPSS is common in advanced chronic liver disease and is associated with the development of hepatic encephalopathy. This study shows that total cross-sectional SPSS area (rather than diameter of the single largest SPSS) predicts survival in patients with advanced chronic liver disease. Our results support the clinical use of total cross-sectional SPSS area for risk stratification and decision-making in the management of SPSS.
Cryptocurrencies have received growing attention from individuals, the media, and regulators. However, little is known about the investors whom these financial instruments attract. Using administrative data, we describe the investment behavior of individuals who invest in cryptocurrencies with structured retail products. We find that cryptocurrency investors are active traders, prone to investment biases, and hold risky portfolios. In line with attention effects and anticipatory utility, we find that the average cryptocurrency investor substantially increases log-in and trading activity after his or her first cryptocurrency purchase. Our results document which investors are more likely to adopt new financial products and help inform regulators about investors' vulnerability to cryptocurrency investments.
The transition from local to global patterns governs the differentiation of mouse blastocysts
(2020)
During mammalian blastocyst development, inner cell mass (ICM) cells differentiate into epiblast (Epi) or primitive endoderm (PrE). These two fates are characterized by the expression of the transcription factors NANOG and GATA6, respectively. Here, we investigate the spatio-temporal distribution of NANOG and GATA6 expressing cells in the ICM of the mouse blastocysts with quantitative three-dimensional single cell-based neighbourhood analyses. We define the cell neighbourhood by local features, which include the expression levels of both fate markers expressed in each cell and its neighbours, and the number of neighbouring cells. We further include the position of a cell relative to the centre of the ICM as a global positional feature. Our analyses reveal a local three-dimensional pattern that is already present in early blastocysts: 1) Cells expressing the highest NANOG levels are surrounded by approximately nine neighbours, while 2) cells expressing GATA6 cluster according to their GATA6 levels. This local pattern evolves into a global pattern in the ICM that starts to emerge in mid blastocysts. We show that FGF/MAPK signalling is involved in the three-dimensional distribution of the cells and, using a mutant background, we further show that the GATA6 neighbourhood is regulated by NANOG. Our quantitative study suggests that the three-dimensional cell neighbourhood plays a role in Epi and PrE precursor specification. Our results highlight the importance of analysing the three-dimensional cell neighbourhood while investigating cell fate decisions during early mouse embryonic development.
How is semantic information stored in the human mind and brain? Some philosophers and cognitive scientists argue for vectorial representations of concepts, where the meaning of a word is represented as its position in a high-dimensional neural state space. At the intersection of natural language processing and artificial intelligence, a class of very successful distributional word vector models has developed that can account for classic EEG findings of language, that is, the ease versus difficulty of integrating a word with its sentence context. However, models of semantics have to account not only for context-based word processing, but should also describe how word meaning is represented. Here, we investigate whether distributional vector representations of word meaning can model brain activity induced by words presented without context. Using EEG activity (event-related brain potentials) collected while participants in two experiments (English and German) read isolated words, we encoded and decoded word vectors taken from the family of prediction-based Word2vec algorithms. We found that, first, the position of a word in vector space allows the prediction of the pattern of corresponding neural activity over time, in particular during a time window of 300 to 500 ms after word onset. Second, distributional models perform better than a human-created taxonomic baseline model (WordNet), and this holds for several distinct vector-based models. Third, multiple latent semantic dimensions of word meaning can be decoded from brain activity. Combined, these results suggest that empiricist, prediction-based vectorial representations of meaning are a viable candidate for the representational architecture of human semantic knowledge.
Background: Naturalistic developmental behavioural interventions (NDBI) have been shown to improve autism-specific symptoms in young children with Autism Spectrum Disorder (ASD). NDBI approaches, such as the ASD-specific Frankfurt Early Intervention Programme for ASD (A-FFIP), are based on ASD-specific developmental and learning aspects. A-FFIP is a low-intensity intervention which can easily be implemented in the local health care/social welfare system. The aim of the present study is to establish 1-year efficacy of the manualised early intervention programme A-FFIP in toddlers and preschool children with ASD. It is hypothesised that A-FFIP will result in improved ASD-specific symptoms compared to early intervention as usual (EIAU). Child- and family-specific secondary outcomes, as well as moderators and mediators of outcome, will be explored.
Methods/design: A prospective, multi-centre, parallel-group, randomised controlled, phase-III trial comparing A-FFIP versus EIAU. A total of 134 children (A-FFIP: 67, EIAU: 67) aged 24–66 months at baseline assessment meeting the criteria for ASD (DSM-5) will be included. The primary outcome is the absolute change of the total score of the Brief Observation of Social Communication Change (BOSCC-AT) between baseline (T2) and 1-year follow-up (T6). The treatment effect will be tested, adjusted for relevant covariates applying a mixed model for repeated measures. Secondary outcomes are BOSCC social communication and repetitive-behaviour scores, single ASD symptoms, language, cognition, psychopathology, parental well-being and family quality of life. Predictors, moderators and mediating mechanisms will be explored.
Discussion: If efficacy of the manualised A-FFIP early intervention is established, the current study has the potential to change clinical practice strongly towards the implementation of a low-intensity, evidence-based, natural early intervention in ASD. Early intervention in ASD requires specialist training, which subsequently needs to be developed or included into current training curricula.
Trial registration: German Registry for Clinical Trials (Deutscher Register Klinischer Studien, DRKS); ID: 00016330. Retrospectively registered on 4 January 2019. URL: https://www.drks.de/drks_web/navigate.do?navigationId=trial.HTML&TRIAL_ID=DRKS00016330.
Background: Depression is a widespread disorder with severe impacts for individuals and society, especially in its chronic form. Current treatment approaches for persistent depression have focused primarily on reducing negative affect and have paid little attention to promoting positive affect. Previous studies have shown that metta meditation increases positive affect in chronically depressed patients. Results from previous trials provide evidence for the efficacy of a stand-alone metta meditation group treatment in combination with mindfulness-based approaches. Further research is needed to better understand the implementation of meditation practice into everyday life. Therefore, mindfulness and metta meditation in a group setting are combined with individual cognitive behavioral therapy (CBT) into a new, low-intensity, cost-effective treatment (“MeCBT”) for chronic depression. Methods/design: In this single-center, randomized, observer-blinded, parallel-group clinical trial we will test the efficacy of MeCBT in reducing depression compared to a wait-list control condition. Forty-eight participants in a balanced design will be allocated randomly to a treatment group or a wait-list control group. Metta-based group meditation will be offered in eight weekly sessions and one additional half-day retreat. Subsequent individual CBT will be conducted in eight fortnightly sessions. Outcome measures will be assessed at four time points: before intervention (T0); after group meditation (T1); after individual CBT (T2); and, in the treated group only, at 6-month follow-up (T3). Changes in depressive symptoms (clinician rating), assessed with the Quick Inventory of Depressive Symptoms (QIDS-C) are the primary outcome. We expect a significant decline of depressive symptoms at T2 compared to the wait-list control group. Secondary outcome measures include self-rated depression, mindfulness, benevolence, rumination, emotion regulation, social connectedness, social functioning, as well as behavioral and cognitive avoidance. We will explore changes at T1 and T2 in all these secondary outcome variables. Discussion: To our knowledge this is the first study to combine a group program focusing on Metta meditation with stateof-the art individual CBT specifically tailored to chronic depression. Implications for further refinement and examination of the treatment program are discussed. Trial registration: ISRCTN, ISRCTN97264476. Registered 29 March 2018 (applied on 14 December 2017)—retrospectively registered.
High-quality single crystals of the unconventional superconductor NdFeAsO1 − xFx were grown. We developed a new optimized flux technique to overcome the difficulties in single-crystal growth and the sample quality limitations of NdFeAsO1 − xFx. The normal state of the F-doped samples exhibits simple metallic behavior upon cooling down from room temperature, followed by a sharp superconducting transition. The values of residual resistivity ratio (RRR) is 3.2, 6.4, and 10.3 for x = 0.1, 0.15, and 0.2, respectively. Both the large RRR and the narrow superconducting transition signpost the high quality of the crystals. We have examined the in- and out-of-plane lower critical fields, and the field at which vortices penetrate the sample of NdFeAsO1 − xFx (x = 0.1). The anisotropy ratio [γHc1 (0)] increased slightly with increasing temperature from 0.8 Tc to Tc. The temperature dependence of the first vortex penetration field was obtained under the static magnetic field, H, parallel to the c- and ab- axis, and pronounced changes in the Hc1(T) curvature were observed, which are attributed to the multi-band superconductivity.
Ferroptosis, a newly discovered form of cell death mediated by reactive oxygen species (ROS) and lipid peroxidation, has recently been shown to have an impact on various cancer types; however, so far there are only few studies about its role in hepatocellular carcinoma (HCC). The delicate equilibrium of ROS in cancer cells has found to be crucial for cell survival, thus increased levels may trigger ferroptosis in HCC.In our study, we investigated the effect of different ROS modulators and ferroptosis inducers on a human HCC cell line and a human hepatoblastoma cell line. We identified a novel synergistic cell death induction by the combination of Auranofin and buthionine sulfoxime (BSO) or by Erastin and BSO at subtoxic concentrations. We found a caspase-independent, redox-regulated cell death, which could be rescued by different inhibitors of ferroptosis. Both cotreatments stimulated lipid peroxidation. All these findings indicated ferroptotic cell death. Both cotreatments affected the canonical ferroptosis pathway through GPX4 downregulation. We also found an accumulation of Nrf2 and HO-1, indicating an additional effect on the non-canonical pathway. Our results implicate that targeting these two main ferroptotic pathways simultaneously can overcome chemotherapy resistance in HCC.
The production of light (anti-)(hyper-)nuclei in heavy-ion collisions at the LHC is considered in the framework of the Saha equation, making use of the analogy between the evolution of the early universe after the Big Bang and that of “Little Bangs” created in the lab. Assuming that disintegration and regeneration reactions involving light nuclei proceed in relative chemical equilibrium after the chemical freeze-out of hadrons, their abundances are determined through the famous cosmological Saha equation of primordial nucleosynthesis and show no exponential dependence on the temperature typical for the thermal model. A quantitative analysis, performed using the hadron resonance gas model in partial chemical equilibrium, shows agreement with experimental data of the ALICE collaboration on d, 3He, HΛ3, and 4He yields for a very broad range of temperatures at T≲155 MeV. The presented picture is supported by the observed suppression of resonance yields in central Pb–Pb collisions at the LHC. Keywords: Light (anti-)(hyper-)nuclei production, Saha equation, Partial chemical equilibrium.
Children with reading and/or spelling disorders have increased rates of behavioral and emotional problems and combinations of these. Some studies also find increased rates of attention-deficit/hyperactivity disorder (ADHD), conduct disorder, anxiety disorder, and depression. However, the comorbidities of, e.g., arithmetic disorders with ADHD, anxiety disorder, and depression have been addressed only rarely. The current study explored the probability of children with specific learning disorders (SLD) in reading, spelling, and/or arithmetic to also have anxiety disorder, depression, ADHD, and/or conduct disorder. The sample consisted of 3,014 German children from grades 3 and 4 (mean age 9;9 years) who completed tests assessing reading, spelling as well as arithmetic achievement and intelligence via a web-based application. Psychopathology was assessed using questionnaires filled in by the parents. In children with a SLD we found high rates of anxiety disorder (21%), depression (28%), ADHD (28%), and conduct disorder (22%). Children with SLD in multiple learning domains had a higher risk for psychopathology and had a broader spectrum of psychopathology than children with an isolated SLD. The results highlight the importance of screening for and diagnosing psychiatric comorbidities in children with SLD.
Polyacrylamide gel electrophoresis (PAGE) and immunoblotting (Western blotting) are the most common methods in life science. In conjunction with these methods, the polyhistidine-tag has proven to be a superb fusion tag for protein purification as well as specific protein detection by immunoblotting, which led to a vast amount of commercially available antibodies. Nevertheless, antibody batch-to-batch variations and nonspecific binding complicate the laborious procedure. The interaction principle applied for His-tagged protein purification by metal-affinity chromatography using N-nitrilotriacetic acid (NTA) was employed to develop small high-affinity lock-and-key molecules coupled to a fluorophore. These multivalent NTA probes allow specific detection of His-tagged proteins by fluorescence. Here, we report on HisQuick-PAGE as a fast and versatile immunoblot alternative, using such high-affinity fluorescent super-chelator probes. The procedure allows direct, fast, and ultra-sensitive in-gel detection and analysis of soluble proteins as well as intact membrane protein complexes and macromolecular ribonucleoprotein particles.
As a relevant cognitive-motivational aspect of ICT literacy, a new construct ICT Engagement is theoretically based on self-determination theory and involves the factors ICT interest, Perceived ICT competence, Perceived autonomy related to ICT use, and ICT as a topic in social interaction. In this manuscript, we present different sources of validity supporting the construct interpretation of test scores in the ICT Engagement scale, which was used in PISA 2015. Specifically, we investigated the internal structure by dimensional analyses and investigated the relation of ICT Engagement aspects to other variables. The analyses are based on public data from PISA 2015 main study from Switzerland (n = 5860) and Germany (n = 6504). First, we could confirm the four-dimensional structure of ICT Engagement for the Swiss sample using a structural equation modelling approach. Second, ICT Engagement scales explained the highest amount of variance in ICT Use for Entertainment, followed by Practical use. Third, we found significantly lower values for girls in all ICT Engagement scales except ICT Interest. Fourth, we found a small negative correlation between the scores in the subscale “ICT as a topic in social interaction” and reading performance in PISA 2015. We could replicate most results for the German sample. Overall, the obtained results support the construct interpretation of the four ICT Engagement subscales.
Imageability and emotionality ratings for 2592 German nouns (3–10 letters, one to three phonological syllables) were obtained from younger adults (21–31 years) and older adults (70–86 years). Valid ratings were obtained on average from 20 younger and 23 older adults per word for imageability, and from 18 younger and 19 older adults per word for emotionality. The internal consistency (Cronbach’s α) and retest rank-order stability of the ratings were high for both age groups (α and r ≥ .97). Also, the validity of our ratings was found to be high, as compared to previously published ratings (r ≥ .86). The ratings showed substantial rank-order stability across younger and older adults (imageability, r = .94; emotionality, r = .85). At the same time, systematic differences between age groups were found in the mean levels of ratings (imageability, d = 0.38; emotionality, d = 0.20) and in the extent to which the rating scales were used (imageability, SD = 24 vs. 19, scale of 0 to 100; emotionality, SD = 26 vs. 31, scale of −100 to 100). At the descriptive level, our data hint at systematically different evaluations of semantic categories regarding imageability and emotionality across younger and older adults. Given that imageability and emotionality have been reported, for instance, as important determinants for the recognition and recall of words, our findings highlight the importance of considering age-specific information in age-comparative cognitive (neuroscience) experimental studies using word materials. The age-specific imageability and emotionality ratings for the 2592 German nouns can be found in the electronic supplementary material...
Ergodic subspace analysis
(2020)
Properties of psychological variables at the mean or variance level can differ between persons and within persons across multiple time points. For example, cross-sectional findings between persons of different ages do not necessarily reflect the development of a single person over time. Recently, there has been an increased interest in the difference between covariance structures, expressed by covariance matrices, that evolve between persons and within a single person over multiple time points. If these structures are identical at the population level, the structure is called ergodic. However, recent data confirms that ergodicity is not generally given, particularly not for cognitive variables. For example, the <i>g</i> factor that is dominant for cognitive abilities between persons seems to explain far less variance when concentrating on a single person’s data. However, other subdimensions of cognitive abilities seem to appear both between and within persons; that is, there seems to be a lower-dimensional subspace of cognitive abilities in which cognitive abilities are in fact ergodic. In this article, we present ergodic subspace analysis (ESA), a mathematical method to identify, for a given set of variables, which subspace is most important within persons, which is most important between person, and which is ergodic. Similar to the common spatial patterns method, the ESA method first whitens a joint distribution from both the between and the within variance structure and then performs a principle component analysis (PCA) on the between distribution, which then automatically acts as an inverse PCA on the within distribution. The difference of the eigenvalues allows a separation of the rotated dimensions into the three subspaces corresponding to within, between, and ergodic substructures. We apply the method to simulated data and to data from the COGITO study to exemplify its usage.
We show that FED policy announcements lead to a significant increase in international comovements in the cross-section of equity and in particular sovereign CDS markets. The relaxation of unconventionary monetary policies is felt strongly by emerging markets, and by countries that are open to the trading of goods and flows, even in the presence of floating exchange rates. It also impacts closed economies whose currencies are pegged to the dollar. This evidence is consistent with recent theories of a global financial cycle and the pricing of a FED’s put. In contrast, ECB announcements hardly affect comovements, even in the Eurozone.
Early experiences of childhood sexual or physical abuse are often associated with functional impairments, reduced well-being and interpersonal problems in adulthood. Prior studies have addressed whether the traumatic experience itself or adult psychopathology is linked to these limitations. To approach this question, individuals with posttraumatic stress disorder (PTSD) and healthy individuals with and without a history of child abuse were investigated. We used global positioning system (GPS) tracking to study temporal and spatial limitations in the participants’ real-life activity space over the course of one week. The sample consisted of 228 female participants: 150 women with PTSD and emotional instability with a history of child abuse, 35 mentally healthy women with a history of child abuse (healthy trauma controls, HTC) and 43 mentally healthy women without any traumatic experiences in their past (healthy controls, HC). Both traumatized groups—i.e. the PTSD and the HTC group—had smaller movement radii than the HC group on the weekends, but neither spent significantly less time away from home than HC. Some differences between PTSD and HC in movement radius seem to be related to correlates of PTSD psychopathology, like depression and physical health. Yet group differences between HTC and HC in movement radius remained even when contextual and individual health variables were included in the model, indicating specific effects of traumatic experiences on activity space. Experiences of child abuse could limit activity space later in life, regardless of whether PTSD develops.
Most human actions produce concomitant sounds. Action sounds can be either part of the action goal (GAS, goal-related action sounds), as for instance in tap dancing, or a mere by-product of the action (BAS, by-product action sounds), as for instance in hurdling. It is currently unclear whether these two types of action sounds—incidental or intentional—differ in their neural representation and whether the impact on the performance evaluation of an action diverges between the two. We here examined whether during the observation of tap dancing compared to hurdling, auditory information is a more important factor for positive action quality ratings. Moreover, we tested whether observation of tap dancing vs. hurdling led to stronger attenuation in primary auditory cortex, and a stronger mismatch signal when sounds do not match our expectations. We recorded individual point-light videos of newly trained participants performing tap dancing and hurdling. In the subsequent functional magnetic resonance imaging (fMRI) session, participants were presented with the videos that displayed their own actions, including corresponding action sounds, and were asked to rate the quality of their performance. Videos were either in their original form or scrambled regarding the visual modality, the auditory modality, or both. As hypothesized, behavioral results showed significantly lower rating scores in the GAS condition compared to the BAS condition when the auditory modality was scrambled. Functional MRI contrasts between BAS and GAS actions revealed higher activation of primary auditory cortex in the BAS condition, speaking in favor of stronger attenuation in GAS, as well as stronger activation of posterior superior temporal gyri and the supplementary motor area in GAS. Results suggest that the processing of self-generated action sounds depends on whether we have the intention to produce a sound with our action or not, and action sounds may be more prone to be used as sensory feedback when they are part of the explicit action goal. Our findings contribute to a better understanding of the function of action sounds for learning and controlling sound-producing actions.
ISOE-Newsletter 02/2020
(2020)
Wasser im Anthropozän – ISOE verlegt Bürger-Uni ins Netz +++ Wie wirkt transdisziplinäre Nachhaltigkeitsforschung? Forschungsprojekt TransImpact gibt Sonderheft der Zeitschrift Environmental Science & Policy heraus +++ Aktuelle Lehrveranstaltungen zur Sozialen Ökologie im Sommersemester 2020 +++ Beteiligungsplattform Weschnitz-Dialog: Begleitprozesse für sozial-ökologische Konflikte an Flüssen +++ Flugscham-Debatte: Wie der öffentliche Diskurs über die Klimawirkungen des Fliegens das Flugverhalten beeinflusst +++ Bodenlos nachhaltig: Neuartige landwirtschaftliche Pflanzenproduktion mit Wasserwiederverwendung +++ Termine +++ Publikationen
Omkāra to Ek Onkāra
(2020)
The facile synthesis and detailed investigation of a class of highly potent protease inhibitors based on 1,4-naphthoquinones with a dipeptidic recognition motif (HN-l-Phe-l-Leu-OR) in the 2-position and an electron-withdrawing group (EWG) in the 3-position is presented. One of the compound representatives, namely the acid with EWG = CN and with R = H proved to be a highly potent rhodesain inhibitor with nanomolar affinity. The respective benzyl ester (R = Bn) was found to be hydrolyzed by the target enzyme itself yielding the free acid. Detailed kinetic and mass spectrometry studies revealed a reversible covalent binding mode. Theoretical calculations with different density functionals (DFT) as well as wavefunction-based approaches were performed to elucidate the mode of action.
Excavation of burrows is an extremely physically demanding activity producing a large amount of metabolic heat. Dissipation of its surplus is crucial to avoid the risk of overheating, but in subterranean mammals it is complicated due to the absence of notable body extremities and high humidity in their burrows. IR-thermography in a previous study on two species of African mole-rats revealed that body heat was dissipated mainly through the ventral body part, which is notably less furred. Here, we analyzed the dorsal and ventral skin morphology, to test if dermal characteristics could contribute to higher heat dissipation through the ventral body part. The thickness of the epidermis and dermis and the presence, extent and connectivity of fat tissue in the dermis were examined using routine histological methods, while vascular density was evaluated using fluorescent dye and confocal microscopy in the giant mole-rat Fukomys mechowii. As in other hitherto studied subterranean mammals, no subcutaneous adipose tissue was found. All examined skin characteristics were very similar for both dorsal and ventral regions: relative content of adipose tissue in the dermis (14.4 ± 3.7% dorsally and 11.0 ± 4.0% ventrally), connectivity of dermal fat (98.5 ± 2.8% and 95.5 ± 6.8%), vascular density (26.5 ± 3.3% and 22.7 ± 2.3%). Absence of large differences in measured characteristics between particular body regions indicates that the thermal windows are determined mainly by the pelage characteristics.
Healthy and degenerating intervertebral discs (IVDs) are innervated by sympathetic nerves, however, adrenoceptor (AR) expression and functionality have never been investigated systematically. Therefore, AR gene expression was analyzed in both tissue and isolated cells from degenerated human IVDs. Furthermore, human IVD samples and spine sections of wildtype mice (WT) and of a mouse line that develops spontaneous IVD degeneration (IVDD, in SM/J mice) were stained for ARs and extracellular matrix (ECM) components. In IVD homogenates and cells α1a-, α1b-, α2a-, α2b-, α2c-, β1-, and β2-AR genes were expressed. In human sections, β2-AR was detectable, and its localization parallels with ECM alterations. Similarly, in IVDs of WT mice, only β2-AR was expressed, and in IVDs of SM/J mice, β2AR expression was stronger accompanied by increased collagen II, collagen XII, decorin as well as decreased cartilage oligomeric matrix protein expression. In addition, norepinephrine stimulation of isolated human IVD cells induced intracellular signaling via ERK1/2 and PKA. For the first time, the existence and functionality of ARs were demonstrated in IVD tissue samples, suggesting that the sympathicus might play a role in IVDD. Further studies will address relevant cellular mechanisms and thereby help to develop novel therapeutic options for IVDD.
The most frequently used boundary-layer turbulence parameterization in numerical weather prediction (NWP) models are turbulence kinetic energy (TKE) based-based schemes. However, these parameterizations suffer from a potential weakness, namely the strong dependence on an ad-hoc quantity, the so-called turbulence length scale. The physical interpretation of the turbulence length scale is difficult and hence it cannot be directly related to measurements or large eddy simulation (LES) data. Consequently, formulations for the turbulence length scale in basically all TKE schemes are based on simplified assumptions and are model-dependent. A good reference for the independent evaluation of the turbulence length scale expression for NWP modeling is missing. Here we propose a new turbulence length scale diagnostic which can be used in the gray zone of turbulence without modifying the underlying TKE turbulence scheme. The new diagnostic is based on the TKE budget: The core idea is to encapsulate the sum of the molecular dissipation and the cross-scale TKE transfer into an effective dissipation, and associate it with the new turbulence length scale. This effective dissipation can then be calculated as a residuum in the TKE budget equation (for horizontal sub-domains of different sizes) using LES data. Estimation of the scale dependence of the diagnosed turbulence length scale using this novel method is presented for several idealized cases.
Knee acoustic emissions provide information about joint health and loading in motion. As the reproducibility of knee acoustic emissions by vibroarthrography is yet unknown, we evaluated the intrasession and interday reliability of knee joint sounds. In 19 volunteers (25.6 ± 2.0 years, 11 female), knee joint sounds were recorded by two acoustic sensors (16,000 Hz; medial tibial plateau, patella). All participants performed four sets standing up/sitting down (five repetitions each). For measuring intrasession reliability, we used a washout phase of 30 min between the first three sets, and for interday reliability we used a washout phase of one week between sets 3 and 4. The mean amplitude (dB) and median power frequency (Hz, MPF) were analyzed for each set. Intraclass correlation coefficients (ICCs (2,1)), standard errors of measurement (SEMs), and coefficients of variability (CVs) were calculated. The intrasession ICCs ranged from 0.85 to 0.95 (tibia) and from 0.73 to 0.87 (patella). The corresponding SEMs for the amplitude were ≤1.44 dB (tibia) and ≤2.38 dB (patella); for the MPF, SEMs were ≤13.78 Hz (tibia) and ≤14.47 Hz (patella). The intrasession CVs were ≤0.06 (tibia) and ≤0.07 (patella) (p < 0.05). The interday ICCs ranged from 0.24 to 0.33 (tibia) and from 0 to 0.82 (patella) for both the MPF and amplitude. The interday SEMs were ≤4.39 dB (tibia) and ≤6.85 dB (patella) for the amplitude and ≤35.39 Hz (tibia) and ≤15.64 Hz (patella) for the MPF. The CVs were ≤0.14 (tibia) and ≤0.08 (patella). Knee joint sounds were highly repeatable within a single session but yielded inconsistent results for the interday reliability.
The purpose of this study was to examine the psychometric properties (i.e., factorial validity, measurement invariance, and reliability) of the Grit-Original scale (Grit-O) within the Netherlands. The Grit-O scale was subjected to a competing measurement modeling strategy that sequentially compared both independent cluster model confirmatory factor analytical- and exploratory structural equation modeling approaches. The results showed that both a two first order, bi-factor structure as well as a less restrictive two factor ESEM factorial structure best-fitted the data. The instrument showed to be reliable at both a lower- (Cronbach’s alpha) and upper-level (composite reliability) limit. However, measurement invariance between genders could only be established for the B-ICM-CFA model. Finally, concurrent validity was established through relating the GRIT-O to task performance. The linear use of the Grit-O scale should therefore carefully be considered.
Context information supports serial dependence of multiple visual objects across memory episodes
(2020)
Serial dependence is thought to promote perceptual stability by compensating for small changes of an object’s appearance across memory episodes. So far, it has been studied in situations that comprised only a single object. The question of how we selectively create temporal stability of several objects remains unsolved. In a memory task, objects can be differentiated by their to-be-memorized feature (content) as well as accompanying discriminative features (context). We test whether congruent context features, in addition to content similarity, support serial dependence. In four experiments, we observe a stronger serial dependence between objects that share the same context features across trials. Apparently, the binding of content and context features is not erased but rather carried over to the subsequent memory episode. As this reflects temporal dependencies in natural settings, our findings reveal a mechanism that integrates corresponding content and context features to support stable representations of individualized objects over time.