Refine
Year of publication
Document Type
- Article (30992) (remove)
Language
- English (16067)
- German (13055)
- Portuguese (584)
- French (385)
- Croatian (251)
- Spanish (242)
- Italian (132)
- Turkish (101)
- Latin (35)
- Multiple languages (35)
Has Fulltext
- yes (30992)
Is part of the Bibliography
- no (30992) (remove)
Keywords
- Deutsch (486)
- taxonomy (454)
- Literatur (288)
- new species (198)
- Hofmannsthal, Hugo von (184)
- Rezeption (155)
- Filmmusik (154)
- Übersetzung (135)
- Vormärz (117)
- morphology (109)
Institute
- Medizin (5449)
- Physik (2063)
- Biowissenschaften (1158)
- Biochemie und Chemie (1116)
- Extern (1069)
- Frankfurt Institute for Advanced Studies (FIAS) (813)
- Gesellschaftswissenschaften (804)
- Geowissenschaften (593)
- Informatik (459)
- Präsidium (453)
Biological drug substance (DS) is often frozen to enhance storage stability, prolong shelf life, and increase flexibility during manufacturing. However, the freezing and thawing (F/T) of bulk DS at the manufacturing scale can impact product quality as a result of various critical conditions, including cryo-concentration during freezing, which are influenced, among other things, by product-independent process parameters (e.g., container type, fill level, F/T equipment, and protocols). In this article, we report the optimization of two major methodologies to study product-independent process parameters in DS bottles at the manufacturing scale, namely the recording of temperature profiles and liquid sampling after thawing to quantify the concentration gradients in the solution. We report experimentally justified measuring positions for temperature recordings, especially for the selection of the last point to freeze position, and highlight the implementation of camera-assisted inspection to determine the last point to thaw and the actual thawing time. In particular, we provide, for the first time, a detailed description of the technical implementation of these two measuring set-ups. Based on the reported case studies, we recommend choosing relevant measuring positions as a result of initial equipment characterization, resulting in a resource-conscious study set-up.
The small GTPases H, K, and NRAS are molecular switches indispensable for proper regulation of cellular proliferation and growth. Several mutations in the genes encoding members of this protein family are associated with cancer and result in aberrant activation of signaling processes caused by a deregulated recruitment of downstream effector proteins. In this study, we engineered variants of the Ras-binding domain (RBD) of the C-Raf proto-oncogene, Ser/Thr kinase (CRAF). These variants bound with high affinity with the effector-binding site of Ras in an active conformation. Structural characterization disclosed how the newly identified RBD mutations cooperate and thereby enhance affinity with the effector-binding site in Ras compared with WT RBD. The engineered RBD variants closely mimicked the interaction mode of naturally occurring Ras effectors and acted as dominant-negative affinity reagents that block Ras signal transduction. Experiments with cancer cells showed that expression of these RBD variants inhibits Ras signaling, reducing cell growth and inducing apoptosis. Using these optimized RBD variants, we stratified patient-derived colorectal cancer organoids with known Ras mutational status according to their response to Ras inhibition. These results revealed that the presence of Ras mutations was insufficient to predict sensitivity to Ras inhibition, suggesting that not all of these tumors required Ras signaling for proliferation. In summary, by engineering the Ras/Raf interface of the CRAF-RBD, we identified potent and selective inhibitors of Ras in its active conformation that outcompete binding of Ras-signaling effectors.
Highlights
• Executive functions contribute to problem-solving in six- to eight-year-olds.
• Working memory and cognitive flexibility contribute to problem-solving.
•Inhibition does not significantly contribute to problem-solving.
Abstract
Previous research has shown that executive functions can contribute to successful problem-solving in preschool and elementary school children. However, most studies did not simultaneously assess the role of different specific aspects of executive functions. Therefore, the aim of our study was to investigate the individual contribution of inhibition, working memory, and cognitive flexibility to science problem-solving performance in elementary school children. A total of 478 children from first and second grades (Mage = 7.44 years) participated in our study. They performed a Go/No-go task (inhibition), a Corsi blocks backward task (working memory), a flexible item selection task (cognitive flexibility), and three science problem-solving tasks, including two gear turning tasks and one stabilization task. Structural equation modeling showed that working memory and cognitive flexibility individually contributed to problem-solving performance, whereas inhibition did not. We conclude that maintaining task requirements and dynamic object relations (working memory) and switching between different problem-solving phases (cognitive flexibility) are essential components of successful science problem-solving in elementary school children. Inhibitory processes may be more relevant in tasks involving a higher degree of interference at the task or response level.
Delegated online search
(2024)
In a delegation problem, a principal P with commitment power tries to pick one out of 𝑛 options. Each option is drawn independently from a known distribution. Instead of inspecting the options herself, P delegates the information acquisition to a rational and self-interested agent A. After inspection, A proposes one of the options, and P can accept or reject. Delegation is a classic setting in economic information design with many prominent applications, but the computational problems are only poorly understood. In this paper, we study a natural online variant of delegation, in which the agent searches through the options in an online fashion. For each option, he has to irrevocably decide if he wants to propose the current option or discard it, before seeing information on the next option(s). How can we design algorithms for P that approximate the utility of her best option in hindsight? We show that in general P can obtain a Θ(1∕𝑛)-approximation and extend this result to ratios of Θ(𝑘∕𝑛) in case (1) A has a lookahead of 𝑘 rounds, or (2) A can propose up to 𝑘 different options. We provide fine-grained bounds independent of 𝑛 based on three parameters. If the ratio of maximum and minimum utility for A is bounded by a factor 𝛼, we obtain an Ω(loglog 𝛼∕ log 𝛼)- approximation algorithm, and we show that this is best possible. Additionally, if P cannot distinguish options with the same value for herself, we show that ratios polynomial in 1∕𝛼 cannot be avoided. If there are at most 𝛽 different utility values for A, we show a Θ(1∕𝛽)-approximation. If the utilities of P and A for each option are related by a factor 𝛾, we obtain an Ω(1∕ log 𝛾)- approximation, where 𝑂(log log 𝛾∕ log 𝛾) is best possible.
Highlights
• Extreme weather events (floods, droughts, extreme heat) impact freshwater ecosystems.
• Effects of extreme events are site-specific, varying by organism traits and site hydrography.
• Cumulative impact of events is more significant than single events' magnitude.
• Temporal dynamics and biological characteristics are crucial for evaluating impacts.
• Freshwater ecosystem resilience depends on complex factors, not just event severity.
Abstract
Understanding the impacts of extreme weather events on freshwater ecosystems is imperative during a time when a multitude of challenges compromises these environments' health. Exploring how such events affect macroinvertebrate communities in rivers sheds light on the resilience of freshwater ecosystems, which is essential for human well-being and biodiversity conservation. In this study, long-term time series of benthic macroinvertebrate communities from four sites along three freshwater streams within the Rhine-Main-Observatory Long-Term Ecological Research site in Germany were analyzed. Each of them was sampled annually over a span of ~20 years to assess the impacts of extreme weather events (floods, droughts, and extreme heat) on macroinvertebrate communities. The findings reveal that the effects of extreme events are site-specific, suggesting that the impacts of an extreme event can vary based on several potential factors, including the life history traits of the organisms within the community and, among others, the hydrography of the site. Moreover, the analysis highlights that the cumulative impact of these events over time is more significant than the impact of a single event's magnitude, while following distinct temporal dynamics. This underscores the importance of considering both the temporal dynamics and the biological characteristics of communities when evaluating the consequences of extreme weather events on biodiversity, illustrating that the resilience of freshwater ecosystems and their biodiversity under such conditions depends on a complex interplay of factors rather than the severity of individual events.
By linearly parameterizing the QCD Landau free energy near the critical point in the baryon chemical potential and temperature plane, we study the fluctuations of the QCD chiral order parameter field (the σ field) in the equilibrium case and dynamical phase transition, respectively. By setting the system size to the typical size of the QGP fireball (≈103 fm3), we show that in the equilibrium case, the discontinuity of the order parameter in the first order phase transition region is replaced by smooth crossover, and the corresponding fluctuations are broadened. Meanwhile, the quartic cumulant κ4 of the σ field is generally negative near the phase transition line. We further derive the dynamical evolution of the QCD Landau free energy in the Fokker-Plank framework, based on which we deduce the dynamical cumulants of the σ field. Assuming the temperature decreases as a known function of time, we numerically evaluate the dynamical cumulants and confirm that the cumulants present clear memory effects. Moreover, the memory effects on the first order phase transition side is stronger than that on the crossover side, and the dynamical cumulants at the hypothetical freeze-out line present rich non-monotonic structures.
Plants and insects often use the same compounds for chemical communication, but not much is known about the genetics of convergent evolution of chemical signals. The terpene (E)-β-ocimene is a common component of floral scent and is also used by the butterfly Heliconius melpomene as an anti-aphrodisiac pheromone. While the biosynthesis of terpenes has been described in plants and microorganisms, few terpene synthases (TPSs) have been identified in insects. Here, we study the recent divergence of 2 species, H. melpomene and Heliconius cydno, which differ in the presence of (E)-β-ocimene; combining linkage mapping, gene expression, and functional analyses, we identify 2 novel TPSs. Furthermore, we demonstrate that one, HmelOS, is able to synthesise (E)-β-ocimene in vitro. We find no evidence for TPS activity in HcydOS (HmelOS ortholog of H. cydno), suggesting that the loss of (E)-β-ocimene in this species is the result of coding, not regulatory, differences. The TPS enzymes we discovered are unrelated to previously described plant and insect TPSs, demonstrating that chemical convergence has independent evolutionary origins.
The dynamic process of membrane shaping and remodeling plays a vital role in cellular functions, with proteins and cellular membranes interacting intricately to adapt to various cellular needs and environmental cues. Ubiquitination—a posttranslational modification—was shown to be essential in regulating membrane structure and shape. It influences virtually all pathways relying on cellular membranes, such as endocytosis and autophagy by directing protein degradation, sorting, and oligomerization. Ubiquitin is mostly known as a protein modifier; however, it was reported that ubiquitin and ubiquitin-like proteins can associate directly with lipids, affecting membrane curvature and dynamics. In this review, we summarize some of the current knowledge on ubiquitin-mediated membrane remodeling in the context of endocytosis, autophagy, and ER-phagy.
The singly Cabibbo-suppressed decay Λ+c→nπ+ is observed for the first time with a statistical significance of 7.3σ by using 3.9 fb−1 of e+e− collision data collected at center-of-mass energies between 4.612 and 4.699 GeV with the BESIII detector at BEPCII. The branching fraction of Λ+c→nπ+ is measured to be (6.6±1.2stat±0.4syst)×10−4. By taking the upper limit of branching fractions of Λ+c→pπ0 from the Belle experiment, the ratio of branching fractions between Λ+c→nπ+ and Λ+c→pπ0 is calculated to be larger than 7.2 at the 90% confidence level, which disagrees with the current predictions of available phenomenological models. In addition, the branching fractions of the Cabibbo-favored decays Λ+c→Λπ+ and Λ+c→Σ0π+ are measured to be (1.31±0.08stat±0.05syst)×10−2 and (1.22±0.08stat±0.07syst)×10−2, respectively, which are consistent with previous results.
Objective: The aim of the study was to find out whether it is possible to successfully convert a communication course for around 400 students to a blended-learning format (asynchronous theoretical course/synchronous digital practical course). The main focus thereby was on assessing subjective learning progress and the extent to which the importance of communication and doctor-patient communication can be conveyed online. The study is based on the results of an evaluation of the opinions of both the students and the lecturers that participated in the course.
Methods: The students, who were in their fourth preclinical semester in 2020, were asked to fill in a self-assessment sheet at the beginning of the course, and following its completion. The feedback provided by the lecturers was also assessed. In order to compare the results and identify possible discrepancies, the corresponding self-assessment and evaluation results for the past 10 years (stemming from traditional classroom courses) were also taken into account.
Results: Participants in the online courses reported distinct subjective learning progress, and greater progress than was reported for traditional courses in previous years. The suitability of the online format was viewed critically by both students and lecturers, while the course atmosphere was seen positively. The relevance of doctor-patient communication was assessed particularly highly in the online format.
Conclusion: Based on the results of the evaluation, the experience gained from the blended-learning format will be included into future iterations of the communication course at Goethe University Frankfurt. The results have shown that doctor-patient communication can be learned well online. This format can therefore be recommended for new learning concepts in the future.
Using a data sample corresponding to an integrated luminosity of 2.93 fb−1 collected at a center-of-mass energy of 3.773~GeV with the BESIII detector at the BEPCII collider, we search for a scalar partner of the X(3872), denoted as X(3700), via ψ(3770)→γηη′ and γπ+π−J/ψ processes. No significant signals are observed and the upper limits of the product branching fractions B(ψ(3770)→γX(3700))⋅B(X(3700)→ηη′) and B(ψ(3770)→γX(3700))⋅B(X(3700)→π+π−J/ψ) are determined at the 90\% confidence level, for the narrow X(3700) with a mass ranging from 3710 to 3740 MeV/c2, which are from 0.8 to 1.8 (×10−5) and 0.9 to 3.4 (×10−5), respectively.
Using 4.7 fb−1 of e+e− collision data at center-of-mass energies from 4.661 to 4.951 GeV collected by the BESIII detector at the BEPCII collider, we observe the X(3872) production process e+e−→ωX(3872) for the first time. The significance is 7.8σ, including both the statistical and systematic uncertainties. The e+e−→ωX(3872) Born cross section and the corresponding upper limit at 90\% confidence level at each energy point are reported. The line shape of the cross section indicates that the ωX(3872) signals may be from the decays of some non-trivial structures.
It usually only takes a single glance to categorize our environment into different scene categories (e.g. a kitchen or a highway). Object information has been suggested to play a crucial role in this process, and some proposals even claim that the recognition of a single object can be sufficient to categorize the scene around it. Here, we tested this claim in four behavioural experiments by having participants categorize real-world scene photographs that were reduced to a single, cut-out object. We show that single objects can indeed be sufficient for correct scene categorization and that scene category information can be extracted within 50 ms of object presentation. Furthermore, we identified object frequency and specificity for the target scene category as the most important object properties for human scene categorization. Interestingly, despite the statistical definition of specificity and frequency, human ratings of these properties were better predictors of scene categorization behaviour than more objective statistics derived from databases of labelled real-world images. Taken together, our findings support a central role of object information during human scene categorization, showing that single objects can be indicative of a scene category if they are assumed to frequently and exclusively occur in a certain environment.
Osteoarthritis of the hip is a common condition that affects older adults. Total hip replacement is the end-stage treatment to relief pain and improve joint function. Little is known about the mechanical load distribution during the activity of bipedal stance, which is an important daily activity for older adults who need to rest more frequently. This study investigated the distribution of the hip and knee joint moments during bipedal stance in patients with unilateral hip osteoarthritis and how the distribution changed 1 year after total hip replacement. Kinematic and kinetic data from bipedal stance were recorded. External hip and knee adduction moments were calculated and load distribution over both limbs was calculated using the symmetry angle. Preoperatively, the non-affected limb carried 10% more body weight than the affected limb when standing on two legs. Moreover, the mean external hip and knee adduction moments of the non-affected limb were increased compared to the affected limb. At follow-up no significant differences were observed between the patients’ limbs. Preoperative and postoperative changes in hip adduction moment were mainly explained by the combination of the vertical ground reaction force and the hip adduction angle. Stance width also explained changes in the hip and knee adduction moments of the affected leg. Furthermore, as with walking, bipedal standing also showed an asymmetric mechanical load distribution in patients with unilateral hip osteoarthritis. Overall, the findings suggest the need for preventive therapy concepts that focus not only on walking but also on optimizing stance towards a balanced load distribution of both legs.
Background: While computed tomography (CT)-guided liver biopsies are commonly performed using unenhanced images, contrast-enhanced images are beneficial for challenging puncture pathways and lesion locations. This study aimed to evaluate the accuracy of CT-guided biopsies for intrahepatic lesions using unenhanced, intravenous (IV)-enhanced, or intra-arterial Lipiodol-marked CT for lesion marking.
Patients and methods: Six-hundred-seven patients (men: 358 [59.0%], mean age 61 years; SD ±12.04) with suspect hepatic lesions and CT-guided liver biopsies were retrospectively evaluated. Successful biopsies were histopathological findings other than typical liver tissue or non-specific findings. Data was ascertained regarding the use of contrast medium for the biopsy-planning CT, unenhanced (group 1) vs. Lipiodol (group 2) vs. IV contrast (group 3). Technical success and influencing factors were insulated. Complications were noted. The results were analyzed using the Wilcoxon-Man-Whitney t-test, Chi-square test, and Spearman-Rho.
Results: Overall lesion hitting rate was 73.1%, with significantly better rates using Lipiodol-marked lesions (79.3%) compared to group 1 (73.8%) and group 3 (65.2%) (p = 0.037). Smaller lesions (<20 mm diameter) benefited significantly from Lipiodol-marking with 71.2% successful biopsy rate compared to group 1 (65.5%) and group 3 (47.7%) (p = 0.021). Liver cirrhosis (p = 0.94) and entity of parenchymal lesions (p = 0.78) had no impact on the hitting rate between the groups. No major complications occurred during the interventions.
Conclusions: Pre-biopsy Lipiodol marking of suspect hepatic lesions significantly increases the lesion-hitting rate and is especially beneficial for biopsy of smaller targets below 20 mm diameter. Further, Lipiodol marking is superior to IV contrast for non-visible lesions in unenhanced CT. Target lesion entity has no impact on the hitting rate.
We search for the process e+e−→π+π−χcJ (J=0,1,2) and for a charged charmonium-like state in the π±χcJ subsystem. The search uses data sets collected with the BESIII detector at the BEPCII storage ring at center-of-mass energies between 4.18 GeV and 4.60 GeV. No significant π+π−χcJ signals are observed at any center-of-mass energy, and thus upper limits are provided which also serve as limits for a possible charmonium-like structure in the invariant π±χcJ mass.
Using data taken at 23 center-of-mass energies between 4.0 and 4.6 GeV with the BESIII detector at the BEPCII collider and with a total integrated luminosity of approximately 15 fb−1, the process e+e−→2(pp¯) is studied for the first time. The Born cross sections for e+e−→2(pp¯) are measured, and no significant structure is observed in the lineshape. The baryon pair (pp and p¯p¯) invariant mass spectra are consistent with phase space, therefore no hexaquark or di-baryon state is found.
How do German general practitioners manage Long-/Post-COVID? A qualitative study in primary care
(2023)
Background: Many patients with ongoing complaints after a SARS-CoV-2 infection are treated in primary care. Existing medical guidelines on how to diagnose and treat Long-/Post-COVID are far from being comprehensive. This study aims to describe how German general practitioners (GPs) deal with this situation, what problems they experience when managing such patients, and how they solve problems associated with the diagnosis and treatment of Long-/Post-COVID.
Methods and Findings: We conducted a qualitative study and interviewed 11 GPs. The most commonly described symptoms were ongoing fatigue, dyspnea, chest tightness and a decrease in physical capacity. The most common way to identify Long-/Post-COVID was by exclusion. Patients suffering from Long-/Post-COVID were generally treated by their GPs and rarely referred. A very common non-pharmacological intervention was to take a wait-and-see approach and grant sick leave. Other non-pharmacological interventions included lifestyle advices, physical exercise, acupuncture and exercises with intense aromas. Pharmacological treatments focused on symptoms, like respiratory symptoms or headaches. Our study’s main limitations are the small sample size and therefore limited generalizability of results.
Conclusions: Further research is required to develop and test pharmaceutical and non-pharmaceutical interventions for patients with Long-/Post-COVID. In addition, strategies to prevent the occurrence of Long-/Post-COVID after an acute infection with SARS-CoV-2 have to be developed. The routine collection of data on the diagnosis and management of Long-/Post-COVID may help in the formulation of best practices. It is up to policymakers to facilitate the necessary implementation of effective interventions in order to limit the huge societal consequences of large groups of patients suffering from Long-/Post-COVID.
We present cross sections for the reaction e+e−→K0SK0L at center-of-mass energies ranging from 3.51 GeV to 4.95 GeV using data samples collected in the BESIII experiment, corresponding to a total integrated luminosity of 26.5 fb−1. The ratio of neutral-to-charged kaon form factors at large momentum transfers (12 GeV2<Q2<25 GeV2) is determined to be 0.21±0.01, which indicates a small but significant effect of flavor-SU(3) breaking in the kaon wave function, and consequently excludes the possibility that flavor-SU(3) breaking is the primary reason for the strong experimental violation of the pQCD prediction |F(π±)|/|F(K±)|=f2π/f2K, where F(π±) and F(K±) are the form factors, and fπ and fK are the decay constants of charged pions and kaons, respectively. We also observe a significant signal for the charmless decay ψ(3770)→K0SK0L for the first time. Within a 1σ contour of the likelihood value, the the branching fraction for ψ(3770)→K0SK0L is determined to be B=(2.63+1.40−1.59)×10−5, and the relative phase between the continuum and ψ(3770) amplitudes is ϕ=(−0.39+0.05−0.10)π. The branching fraction is in good agreement with the S- and D-wave charmonia mixing scheme proposed in the interpretation of the "ρπ puzzle" between J/ψ and ψ(3686) decays.