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Somatosensory input generated by one's actions (i.e., self-initiated body movements) is generally attenuated. Conversely, externally caused somatosensory input is enhanced, for example, during active touch and the haptic exploration of objects. Here, we used functional magnetic resonance imaging (fMRI) to ask how the brain accomplishes this delicate weighting of self-generated versus externally caused somatosensory components. Finger movements were either self-generated by our participants or induced by functional electrical stimulation (FES) of the same muscles. During half of the trials, electrotactile impulses were administered when the (actively or passively) moving finger reached a predefined flexion threshold. fMRI revealed an interaction effect in the contralateral posterior insular cortex (pIC), which responded more strongly to touch during self-generated than during FES-induced movements. A network analysis via dynamic causal modeling revealed that connectivity from the secondary somatosensory cortex via the pIC to the supplementary motor area was generally attenuated during self-generated relative to FES-induced movements-yet specifically enhanced by touch received during self-generated, but not FES-induced movements. Together, these results suggest a crucial role of the parietal operculum and the posterior insula in differentiating self-generated from externally caused somatosensory information received from one's moving limb.
In two experiments, we compared the dynamics of corticospinal excitability when processing visually or linguistically presented tool-oriented hand actions in native speakers and sequential bilinguals. In a third experiment we used the same procedure to test non-motor, low-level stimuli, i.e. scrambled images and pseudo-words.
Stimuli were presented in sequence: pictures (tool + tool-oriented hand action or their scrambled counterpart) and words (tool noun + tool-action verb or pseudo-words). Experiment 1 presented German linguistic stimuli to native speakers, while Experiment 2 presented English stimuli to non-natives. Experiment 3 tested Italian native speakers. Single-pulse trascranial magnetic stimulation (spTMS) was applied to the left motor cortex at five different timings: baseline, 200 ms after tool/noun onset, 150, 350 and 500 ms after hand/verb onset with motor-evoked potentials (MEPs) recorded from the first dorsal interosseous (FDI) and abductor digiti minimi (ADM) muscles.
We report strong similarities in the dynamics of corticospinal excitability across the visual and linguistic modalities. MEPs' suppression started as early as 150 ms and lasted for the duration of stimulus presentation (500 ms). Moreover, we show that this modulation is absent for stimuli with no motor content. Overall, our study supports the notion of a core, overarching system of action semantics shared by different modalities.
This paper investigates the predictions of the Derivational Complexity Hypothesis by studying the acquisition of wh-questions in 4- and 5-year-old Akan-speaking children in an experimental approach using an elicited production and an elicited imitation task. Akan has two types of wh-question structures (wh-in-situ and wh-ex-situ questions), which allows an investigation of children’s acquisition of these two question structures and their preferences for one or the other. Our results show that adults prefer to use wh-ex-situ questions over wh-in-situ questions. The results from the children show that both age groups have the two question structures in their linguistic repertoire. However, they differ in their preferences in usage in the elicited production task: while the 5-year-olds preferred the wh-in-situ structure over the wh-ex-situ structure, the 4-year-olds showed a selective preference for the wh-in-situ structure in who-questions. These findings suggest a developmental change in wh-question preferences in Akan-learning children between 4 and 5 years of age with a so far unobserved u-shaped developmental pattern. In the elicited imitation task, all groups showed a strong tendency to maintain the structure of in-situ and ex-situ questions in repeating grammatical questions. When repairing ungrammatical ex-situ questions, structural changes to grammatical in-situ questions were hardly observed but the insertion of missing morphemes while keeping the ex-situ structure. Together, our findings provide only partial support for the Derivational Complexity Hypothesis.
Macrophages have important protective functions during infection with herpes simplex virus type 1 (HSV-1). However, molecular mechanisms that restrict viral propagation and protect from severe disease are unclear. Here we show that macrophages take up HSV-1 via endocytosis and transport the virions into multivesicular bodies (MVBs). In MVBs, acid ceramidase (aCDase) converts ceramide into sphingosine and increases the formation of sphingosine-rich intraluminal vesicles (ILVs). Once HSV-1 particles reach MVBs, sphingosine-rich ILVs bind to HSV-1 particles, which restricts fusion with the limiting endosomal membrane and prevents cellular infection. Lack of aCDase in macrophage cultures or in Asah1(-/-) mice results in replication of HSV-1 and Asah1(-/-) mice die soon after systemic or intravaginal inoculation. The treatment of macrophages with sphingosine enhancing compounds blocks HSV-1 propagation, suggesting a therapeutic potential of this pathway. In conclusion, aCDase loads ILVs with sphingosine, which prevents HSV-1 capsids from penetrating into the cytosol.
The application of inhomogeneous AC electric fields for molecular immobilization is a very fast and simple method that does not require any adaptions to the molecule's functional groups or charges. Here, the method is applied to a completely new category of molecules: small organic fluorescence dyes, whose dimensions amount to only 1 nm or even less. The presented setup and the electric field parameters used allow immobilization of dye molecules on the whole electrode surface as opposed to pure dielectrophoretic applications, where molecules are attracted only to regions of high electric field gradients, i.e., to the electrode tips and edges. In addition to dielectrophoresis and AC electrokinetic flow, molecular scale interactions and electrophoresis at short time scales are discussed as further mechanisms leading to migration and immobilization of the molecules.
For hybrid organic-inorganic as well as all-inorganic lead halide perovskites a Rashba effect has been invoked to explain the high efficiency in energy conversion by prohibiting direct recombination. Both a bulk and surface Rashba effect have been predicted. In the valence band of methylammonium (MA) lead bromide a Rashba effect has been reported by angle-resolved photoemission and circular dichroism with giant values of 7-11 eV angstrom. We present band dispersion measurements of MAPbBr(3) and spin-resolved photoemission of CsPbBr3 to show that a large Rashba effect detectable by photoemission or circular dichroism does not exist and cannot be the origin of the high effciency.
ABCB1/4 gallbladder cancer risk variants identified in India also show strong effects in Chileans
(2020)
Background: The first large-scale genome-wide association study of gallbladder cancer (GBC) recently identified and validated three susceptibility variants in the ABCB1 and ABCB4 genes for individuals of Indian descent. We investigated whether these variants were also associated with GBC risk in Chileans, who show the highest incidence of GBC worldwide, and in Europeans with a low GBC incidence.
Methods: This population-based study analysed genotype data from retrospective Chilean case-control (255 cases, 2042 controls) and prospective European cohort (108 cases, 181 controls) samples consistently with the original publication.
Results: Our results confirmed the reported associations for Chileans with similar risk effects. Particularly strong associations (per-allele odds ratios close to 2) were observed for Chileans with high Native American (=Mapuche) ancestry. No associations were noticed for Europeans, but the statistical power was low.
Conclusion: Taking full advantage of genetic and ethnic differences in GBC risk may improve the efficiency of current prevention programs.
We analyze the spatiotemporal evolution of seismicity during a sequence of moderate (an M-w 4.7 foreshock and M-w 5.8 mainshock) earthquakes occurring in September 2019 at the transition between a creeping and a locked segment of the North Anatolian fault in the central Sea of Marmara, northwest Turkey. To investigate in detail the seismicity evolution, we apply a matched-filter technique to continuous waveforms, thus reducing the magnitude threshold for detection. Sequences of foreshocks preceding the two largest events are clearly seen, exhibiting two different behaviors: a long-term activation of the seismicity along the entire fault segment and a short-term concentration around the epicenters of the large events. We suggest a two-scale preparation phase, with aseismic slip preparing the mainshock final rupture a few days before, and a cascade mechanism leading to the nucleation of the mainshock. Thus, our study shows a combination of seismic and aseismic slip during the foreshock sequence changing the strength of the fault, bringing it closer to failure.
Schema modes (ormodes) are a key concept in the theory underlying schema therapy. Modes have rarely been related to established models of personality traits. The present study thus investigates the associations between trait emotional intelligence (TEI) and 14 modes, and tests a global TEI-mode factors-general psychological distress mediation model. The study draws on self-report data from 173 inpatients from a German clinic for psychosomatic medicine. Global TEI correlated positively with both healthy modes (happy child and healthy adult) and negatively with 10 maladaptive modes. When modes were regressed on the four TEI factors, six (emotionality), five (well-being), four (sociability), and four (self-control) significant partial effects on 10 modes emerged. In the parallel mediation model, the mode factors internalization and compulsivity fully mediated the global TEI-general psychological distress link. Implications of the results for the integration of modes with traits in general and with TEI in particular as well as implications of low TEI as a transdiagnostic feature of personality malfunctioning are discussed.
A treemap is a visualization that has been specifically designed to facilitate the exploration of tree-structured data and, more general, hierarchically structured data. The family of visualization techniques that use a visual metaphor for parent-child relationships based “on the property of containment” (Johnson, 1993) is commonly referred to as treemaps. However, as the number of variations of treemaps grows, it becomes increasingly important to distinguish clearly between techniques and their specific characteristics. This paper proposes to discern between Space-filling Treemap TS, Containment Treemap TC, Implicit Edge Representation Tree TIE, and Mapped Tree TMT for classification of hierarchy visualization techniques and highlights their respective properties. This taxonomy is created as a hyponymy, i.e., its classes have an is-a relationship to one another: TS TC TIE TMT. With this proposal, we intend to stimulate a discussion on a more unambiguous classification of treemaps and, furthermore, broaden what is understood by the concept of treemap itself.
Pollen records from Siberia are mostly absent in global or Northern Hemisphere synthesis works. Here we present a taxonomically harmonized and temporally standardized pollen dataset that was synthesized using 173 palynological records from Siberia and adjacent areas (northeastern Asia, 42-75 degrees N, 50-180 degrees E). Pollen data were taxonomically harmonized, i.e. the original 437 taxa were assigned to 106 combined pollen taxa. Age-depth models for all records were revised by applying a constant Bayesian age-depth modelling routine. The pollen dataset is available as count data and percentage data in a table format (taxa vs. samples), with age information for each sample. The dataset has relatively few sites covering the last glacial period between 40 and 11.5 ka (calibrated thousands of years before 1950 CE) particularly from the central and western part of the study area. In the Holocene period, the dataset has many sites from most of the area, with the exception of the central part of Siberia. Of the 173 pollen records, 81 % of pollen counts were downloaded from open databases (GPD, EPD, PANGAEA) and 10 % were contributions by the original data gatherers, while a few were digitized from publications. Most of the pollen records originate from peatlands (48 %) and lake sediments (33 %). Most of the records (83 %) have >= 3 dates, allowing the establishment of reliable chronologies. The dataset can be used for various purposes, including pollen data mapping (example maps for Larix at selected time slices are shown) as well as quantitative climate and vegetation reconstructions. The datasets for pollen counts and pollen percentages are available at https://doi.org/10.1594/PANGAEA.898616 (Cao et al., 2019a), also including the site information, data source, original publication, dating data, and the plant functional type for each pollen taxa.
Most South Asian countries have challenges in ensuring water, energy, and food (WEF) security, which are often interacting positively or negatively. To address these challenges, the nexus approach provides a framework to identify the interactions of the WEF sectors as an integrated system. However, most nexus studies only qualitatively discuss the interactions between these sectors. This study conducts a systematic analysis of the WEF security nexus in South Asia by using open data sources at the country scale. We analyze interactions between the WEF sectors statistically, defining positive and negative correlations between the WEF security indicators as synergies and trade-offs, respectively. By creating networks of the synergies and trade-offs, we further identify most positively and negatively influencing indicators in the WEF security nexus. We observe a larger share of trade-offs than synergies within the water and energy sectors and a larger share of synergies than trade-offs among the WEF sectors for South Asia. However, these observations vary across the South Asian countries. Our analysis highlights that strategies on promoting sustainable energy and discouraging fossil fuel use could have overall positive effects on the WEF security nexus in the countries. This study provides evidence for considering the WEF security nexus as an integrated system rather than just a combination of three different sectors or securities.
Context
The recently claimed discovery of a massive (M-BH = 68(-13)(+11) M-circle dot) black hole in the Galactic solar neighborhood has led to controversial discussions because it severely challenges our current view of stellar evolution.
Aims
A crucial aspect for the determination of the mass of the unseen black hole is the precise nature of its visible companion, the B-type star LSV +22 25. Because stars of different mass can exhibit B-type spectra during the course of their evolution, it is essential to obtain a comprehensive picture of the star to unravel its nature and, thus, its mass.
Methods
To this end, we study the spectral energy distribution of LSV +22 25 and perform a quantitative spectroscopic analysis that includes the determination of chemical abundances for He, C, N, O, Ne, Mg, Al, Si, S, Ar, and Fe.
Results
Our analysis clearly shows that LSV +22 25 is not an ordinary main sequence B-type star. The derived abundance pattern exhibits heavy imprints of the CNO bi-cycle of hydrogen burning, that is, He and N are strongly enriched at the expense of C and O. Moreover, the elements Mg, Al, Si, S, Ar, and Fe are systematically underabundant when compared to normal main-sequence B-type stars. We suggest that LSV +22 25 is a stripped helium star and discuss two possible formation scenarios. Combining our photometric and spectroscopic results with the Gaia parallax, we infer a stellar mass of 1.1 +/- 0.5 M-circle dot. Based on the binary system's mass function, this yields a minimum mass of 2-3 M-circle dot for the compact companion, which implies that it may not necessarily be a black hole but a massive neutron- or main sequence star.
Conclusions
The star LSV +22 25 has become famous for possibly having a very massive black hole companion. However, a closer look reveals that the star itself is a very intriguing object. Further investigations are necessary for complete characterization of this object.
Other than commonly assumed in seismology, the phase velocity of Rayleigh waves is not necessarily a single-valued function of frequency. In fact, a single Rayleigh mode can exist with three different values of phase velocity at one frequency. We demonstrate this for the first higher mode on a realistic shallow seismic structure of a homogeneous layer of unconsolidated sediments on top of a half-space of solid rock (LOH). In the case of LOH a significant contrast to the half-space is required to produce the phenomenon. In a simpler structure of a homogeneous layer with fixed (rigid) bottom (LFB) the phenomenon exists for values of Poisson's ratio between 0.19 and 0.5 and is most pronounced for P-wave velocity being three times S-wave velocity (Poisson's ratio of 0.4375). A pavement-like structure (PAV) of two layers on top of a half-space produces the multivaluedness for the fundamental mode. Programs for the computation of synthetic dispersion curves are prone to trouble in such cases. Many of them use mode-follower algorithms which loose track of the dispersion curve and miss the multivalued section. We show results for well established programs. Their inability to properly handle these cases might be one reason why the phenomenon of multivaluedness went unnoticed in seismological Rayleigh wave research for so long. For the very same reason methods of dispersion analysis must fail if they imply wave number k(l)(omega) for the lth Rayleigh mode to be a single-valued function of frequency.. This applies in particular to deconvolution methods like phase-matched filters. We demonstrate that a slant-stack analysis fails in the multivalued section, while a Fourier-Bessel transformation captures the complete Rayleigh-wave signal. Waves of finite bandwidth in the multivalued section propagate with positive group-velocity and negative phase-velocity. Their eigenfunctions appear conventional and contain no conspicuous feature.
A shelter for the future
(2020)
Plant development in its majority occurs post-embryonically
through the activity of local meristems that provide daughter cells
for the development of new organs. It has long been acknowledged
that the shoot apical meristem (SAM), which holds the stem cells
that will form above-ground organs, is recalcitrant to infection by
multiple pathogens, a crucial strategy to safeguard normal devel-
opment and subsequent generations. However, the molecular
mechanisms underlying SAM immunity remain largely unknown.
This paper analyzes a specific section of Martial’s Apophoreta (Book 14), the ‘list’ of fourteen literary works that the poet-persona suggests to the reader as potentially suitable presents to give to friends on the occasion of the Saturnalia. It focuses strictly on the literary aspects of the poems and their underlying carnivalesque poetics. This includes an assessment of the logic of the poems’ arrangement and alleged inconsistencies. It is suggested that the section be read as a complex statement of Martial’s on various works and genres of Greek and Roman literature. The last couplet of the section (14.196), a certain Calvus’ work ‘On the use of cold water’ (De aquae frigidae usu), which is unidentifiable, receives particular attention, for previous scholarship has wasted a lot of ink on guessing what kind of work this may have been, thereby losing touch with the rich (meta-)poetics the couplet actually conveys.
The study of the Cauchy problem for solutions of the heat equation in a cylindrical domain with data on the lateral surface by the Fourier method raises the problem of calculating the inverse Laplace transform of the entire function cos root z. This problem has no solution in the standard theory of the Laplace transform. We give an explicit formula for the inverse Laplace transform of cos root z using the theory of analytic functionals. This solution suits well to efficiently develop the regularization of solutions to Cauchy problems for parabolic equations with data on noncharacteristic surfaces.
We study the source properties of the 2005 Kashmir earthquake and its aftershocks to unravel the seismotectonics of the NW Himalayan syntaxis. The mainshock and larger aftershocks have been simultaneously relocated using phase data. We use back-projection of high-frequency energy from multiple teleseismic arrays to model the spatio-temporal evolution of the mainshock rupture. Our analysis reveal a bilateral rupture, which initially propagated SE and then NW of the epicenter, with an average rupture velocity of similar to 2 km s(-1). The area of maximum energy release is parallel to and bound by the surface rupture. Incorporating rupture propagation and velocity, we model the mainshock as a line source using P- and SH-waveform inversion. Our result confirms that the mainshock occurred on a NE dipping (similar to 35 degrees) fault plane, with centroid depth of similar to 10 km. Integrated source time function show that majority of the energy was released in the first similar to 20 s, and was confined above the hypocenter. From waveform inverted fault dimension and seismic moment, we argue that the mainshock had an additional similar to 25 km blind rupture beyond the NW Himalayan syntaxis. Combining this with findings from previous studies, we conjecture that the blind rupture propagated NW of the syntaxis underneath a weak detachment overlain by infra-Cambrian salt layer, and terminated in a wedge thrust. All moderate-to-large aftershocks, NW of the mainshock rupture, are concentrated at the edge of the blind rupture termination. Source modeling of these aftershocks reveal thrust mechanism with centroid depths of 2-10 km, and fault planes oriented subparallel to the mainshock rupture. To study the influence of mainshock rupture on aftershock occurrence, we compute Coulomb failure stress on aftershock faults. All these aftershocks lie in the positive Coulomb stress change region. This suggest that the aftershocks have been triggered by either co-seismic or post-seismic slip on the mainshock fault.
Subdwarf B stars are core-helium-burning stars located on the extreme horizontal branch (EHB). Extensive mass loss on the red giant branch is necessary to form them. It has been proposed that substellar companions could lead to the required mass loss when they are engulfed in the envelope of the red giant star. J08205+0008 was the first example of a hot subdwarf star with a close, substellar companion candidate to be found. Here, we perform an in-depth re-analysis of this important system with much higher quality data allowing additional analysis methods. From the higher resolution spectra obtained with ESO-VLT/XSHOOTER, we derive the chemical abundances of the hot subdwarf as well as its rotational velocity. Using the Gaia parallax and a fit to the spectral energy distribution in the secondary eclipse, tight constraints to the radius of the hot subdwarf are derived. From a long-term photometric campaign, we detected a significant period decrease of -3.2(8) x 10(-12) dd(-1). This can be explained by the non-synchronized hot subdwarf star being spun up by tidal interactions forcing it to become synchronized. From the rate of period decrease we could derive the synchronization time-scale to be 4 Myr, much smaller than the lifetime on EHB. By combining all different methods, we could constrain the hot subdwarf to a mass of 0.39-0.50 M-circle dot and a radius of R-sdB = 0.194 +/- 0.008 R-circle dot, and the companion to 0.061-0.071 M-circle dot with a radius of R-comp = 0.092 +/- 0.005 R-circle dot, below the hydrogen-burning limit. We therefore confirm that the companion is most likely a massive brown dwarf.
A Prophet of Divine Wisdom?
(2020)
In the nineteenth century, the reception of Giambattista Vico’s writings came along with nationalist interpretations of his Scienza Nuova as an ‘Italian Science’. This tendency was based upon an increased examination of the role that the philosopher Pythagoras and his Italian school of Croton played in Vico’s hierarchical conception of the ancient Greek and Italian civilizations. Writers, archaeologists and historians used the New Science as a metonymic reference work for their own nationalist concepts by updating the Pythagorean myth in accordance with relevant narratives of exclusive genealogies concerning an ancient Italian wisdom. These narratives follow tendencies in Vico’s own writings that were quoted strategically and mixed with further interpretations of the Scienza Nuova as reliable testimonial for a glorious Italian history. A theological poet characterized by deeper insight into the secrets of nature and some parts of the divine providence, Pythagoras gains his special position in Vico’s general conception of knowledge.
Residential assets, comprising buildings and household contents, are a major source of direct flood losses. Existing damage models are mostly deterministic and limited to particular countries or flood types. Here, we compile building-level losses from Germany, Italy and the Netherlands covering a wide range of fluvial and pluvial flood events. Utilizing a Bayesian network (BN) for continuous variables, we find that relative losses (i.e. loss relative to exposure) to building structure and its contents could be estimated with five variables: water depth, flow velocity, event return period, building usable floor space area and regional disposable income per capita. The model's ability to predict flood losses is validated for the 11 flood events contained in the sample. Predictions for the German and Italian fluvial floods were better than for pluvial floods or the 1993 Meuse river flood. Further, a case study of a 2010 coastal flood in France is used to test the BN model's performance for a type of flood not included in the survey dataset. Overall, the BN model achieved better results than any of 10 alternative damage models for reproducing average losses for the 2010 flood. An additional case study of a 2013 fluvial flood has also shown good performance of the model. The study shows that data from many flood events can be combined to derive most important factors driving flood losses across regions and time, and that resulting damage models could be applied in an open data framework.
Among theories of human language comprehension, cue-based memory retrieval has proven to be a useful framework for understanding when and how processing difficulty arises in the resolution of long-distance dependencies. Most previous work in this area has assumed that very general retrieval cues like [+subject] or [+singular] do the work of identifying (and sometimes misidentifying) a retrieval target in order to establish a dependency between words. However, recent work suggests that general, handpicked retrieval cues like these may not be enough to explain illusions of plausibility (Cunnings & Sturt, 2018), which can arise in sentences like The letter next to the porcelain plate shattered. Capturing such retrieval interference effects requires lexically specific features and retrieval cues, but handpicking the features is hard to do in a principled way and greatly increases modeler degrees of freedom. To remedy this, we use well-established word embedding methods for creating distributed lexical feature representations that encode information relevant for retrieval using distributed retrieval cue vectors. We show that the similarity between the feature and cue vectors (a measure of plausibility) predicts total reading times in Cunnings and Sturt's eye-tracking data. The features can easily be plugged into existing parsing models (including cue-based retrieval and self-organized parsing), putting very different models on more equal footing and facilitating future quantitative comparisons.
We consider a perturbation of the de Rham complex on a compact manifold with boundary. This perturbation goes beyond the framework of complexes, and so cohomology does not apply to it. On the other hand, its curvature is "small", hence there is a natural way to introduce an Euler characteristic and develop a Lefschetz theory for the perturbation. This work is intended as an attempt to develop a cohomology theory for arbitrary sequences of linear mappings.
Matching participants (as suggested by Hope, 2015) may be one promising option for research on a potential bilingual advantage in executive functions (EF). In this study we first compared performances in three EF-tasks of a naturally heterogeneous sample of monolingual (n = 69, age = 9.0 y) and multilingual children (n = 57, age = 9.3 y). Secondly, we meticulously matched participants pairwise to obtain two highly homogeneous groups to rerun our analysis and investigate a potential bilingual advantage. The initally disadvantaged multilinguals (regarding socioeconomic status and German lexicon size) performed worse in updating and response inhibition, but similarly in interference inhibition. This indicates that superior EF compensate for the detrimental effects of the background variables. After matching children pairwise on age, gender, intelligence, socioeconomic status and German lexicon size, performances became similar except for interference inhibition. Here, an advantage for multilinguals in the form of globally reduced reaction times emerged, indicating a bilingual executive processing advantage.
Whereas self-propelled hard discs undergo motility-induced phase separation, self-propelled rods exhibit a variety of nonequilibrium phenomena, including clustering, collective motion, and spatio-temporal chaos. In this work, we present a theoretical framework representing active particles by continuum fields. This concept combines the simplicity of alignment-based models, enabling analytical studies, and realistic models that incorporate the shape of self-propelled objects explicitly. By varying particle shape from circular to ellipsoidal, we show how nonequilibrium stresses acting among self-propelled rods destabilize motility-induced phase separation and facilitate orientational ordering, thereby connecting the realms of scalar and vectorial active matter. Though the interaction potential is strictly apolar, both, polar and nematic order may emerge and even coexist. Accordingly, the symmetry of ordered states is a dynamical property in active matter. The presented framework may represent various systems including bacterial colonies, cytoskeletal extracts, or shaken granular media. Interacting self-propelled particles exhibit phase separation or collective motion depending on particle shape. A unified theory connecting these paradigms represents a major challenge in active matter, which the authors address here by modeling active particles as continuum fields.
The use of monoclonal antibodies is ubiquitous in science and biomedicine but the generation and validation process of antibodies is nevertheless complicated and time-consuming. To address these issues we developed a novel selective technology based on an artificial cell surface construct by which secreted antibodies were connected to the corresponding hybridoma cell when they possess the desired antigen-specificity. Further the system enables the selection of desired isotypes and the screening for potential cross-reactivities in the same context. For the design of the construct we combined the transmembrane domain of the EGF-receptor with a hemagglutinin epitope and a biotin acceptor peptide and performed a transposon-mediated transfection of myeloma cell lines. The stably transfected myeloma cell line was used for the generation of hybridoma cells and an antigen- and isotype-specific screening method was established. The system has been validated for globular protein antigens as well as for haptens and enables a fast and early stage selection and validation of monoclonal antibodies in one step.
A novel design of an electrochemical anodization cell dedicated to the synthesis of mesoporous, single-crystalline silicon is presented. First and foremost, the design principle follows user safety since electrochemical etching of silicon requires highly hazardous electrolytes based on hydrofluoric (HF) acid. The novel cell design allows for safe electrolyte handling prior, during, and post-etching. A peristaltic pump with HF-resistant fluoroelastomer tubing transfers electrolytes between dedicated reservoirs and the anodization cell. Due to the flexibility of the cell operation, different processing conditions can be realized providing a large parameter range for the attainable sample thickness, its porosity, and the mean pore size. Rapid etching on the order of several minutes to synthesize micrometer-thick porous silicon epilayers on bulk silicon is possible as well as long-time etching with continuous, controlled electrolyte flow for several days to prepare up to 1000 mu m thick self-supporting porous silicon membranes. A highly adaptable, LabVIEW((TM))-based control software allows for user-defined etching profiles.
Motivated by the observation of non-exponential run-time distributions of bacterial swimmers, we propose a minimal phenomenological model for taxis of active particles whose motion is controlled by an internal clock. The ticking of the clock depends on an external concentration field, e.g., a chemical substance. We demonstrate that these particles can detect concentration gradients and respond to them by moving up- or down-gradient depending on the clock design, albeit measurements of these fields are purely local in space and instantaneous in time. Altogether, our results open a new route in the study of directional navigation: we show that the use of a clock to control motility actions represents a generic and versatile toolbox to engineer behavioral responses to external cues, such as light, chemical, or temperature gradients.
Here, a promising approach for producing piezo-polymer transducers in a one-step process is presented. Using 3D-printing technology and polypropylene (PP) filaments, we are able to print a two-layered film structure with regular cavities of precisely controlled size and shape. It is found that the 3D-printed samples exhibit piezoelectric coefficients up to 200 pC/N, similar to those of other PP ferroelectrets, and their temporal and thermal behavior is in good agreement with those known of PP ferroelectrets. The piezoelectric response strongly decreases for applied pressures above 20 kPa, as the pressure in the air-filled cavities strongly influences the overall elastic modulus of ferroelectrets.
Metagenomic sequencing has revolutionised our knowledge of virus diversity, with new virus sequences being reported faster than ever before. However, virus discovery from metagenomic sequencing usually depends on detectable homology: without a sufficiently close relative, so-called ‘dark’ virus sequences remain unrecognisable. An alternative approach is to use virus-identification methods that do not depend on detecting homology, such as virus recognition by host antiviral immunity. For example, virus-derived small RNAs have previously been used to propose ‘dark’ virus sequences associated with the Drosophilidae (Diptera). Here, we combine published Drosophila data with a comprehensive search of transcriptomic sequences and selected meta-transcriptomic datasets to identify a completely new lineage of segmented positive-sense single-stranded RNA viruses that we provisionally refer to as the Quenyaviruses. Each of the five segments contains a single open reading frame, with most encoding proteins showing no detectable similarity to characterised viruses, and one sharing a small number of residues with the RNA-dependent RNA polymerases of single- and double-stranded RNA viruses. Using these sequences, we identify close relatives in approximately 20 arthropods, including insects, crustaceans, spiders, and a myriapod. Using a more conserved sequence from the putative polymerase, we further identify relatives in meta-transcriptomic datasets from gut, gill, and lung tissues of vertebrates, reflecting infections of vertebrates or of their associated parasites. Our data illustrate the utility of small RNAs to detect viruses with limited sequence conservation, and provide robust evidence for a new deeply divergent and phylogenetically distinct RNA virus lineage.
Anthropogenic changes in climate, land use, and disturbance regimes, as well as introductions of non-native species can lead to the transformation of many ecosystems. The resulting novel ecosystems are usually characterized by species assemblages that have not occurred previously in a given area. Quantifying the ecological novelty of communities (i.e., biotic novelty) would enhance the understanding of environmental change. However, quantification remains challenging since current novelty metrics, such as the number and/or proportion of non-native species in a community, fall short of considering both functional and evolutionary aspects of biotic novelty. Here, we propose the Biotic Novelty Index (BNI), an intuitive and flexible multidimensional measure that combines (a) functional differences between native and non-native introduced species with (b) temporal dynamics of species introductions. We show that the BNI is an additive partition of Rao's quadratic entropy, capturing the novel interaction component of the community's functional diversity. Simulations show that the index varies predictably with the relative amount of functional novelty added by recently arrived species, and they illustrate the need to provide an additional standardized version of the index. We present a detailed R code and two applications of the BNI by (a) measuring changes of biotic novelty of dry grassland plant communities along an urbanization gradient in a metropolitan region and (b) determining the biotic novelty of plant species assemblages at a national scale. The results illustrate the applicability of the index across scales and its flexibility in the use of data of different quality. Both case studies revealed strong connections between biotic novelty and increasing urbanization, a measure of abiotic novelty. We conclude that the BNI framework may help building a basis for better understanding the ecological and evolutionary consequences of global change.
Investigation of processes that contribute to the maintenance of genomic stability is one crucial factor in the attempt to understand mechanisms that facilitate ageing. The DNA damage response (DDR) and DNA repair mechanisms are crucial to safeguard the integrity of DNA and to prevent accumulation of persistent DNA damage. Among them, base excision repair (BER) plays a decisive role. BER is the major repair pathway for small oxidative base modifications and apurinic/apyrimidinic (AP) sites. We established a highly sensitive non-radioactive assay to measure BER incision activity in murine liver samples. Incision activity can be assessed towards the three DNA lesions 8-oxo-2’-deoxyguanosine (8-oxodG), 5-hydroxy-2’-deoxyuracil (5-OHdU), and an AP site analogue. We applied the established assay to murine livers of adult and old mice of both sexes. Furthermore, poly(ADP-ribosyl)ation (PARylation) was assessed, which is an important determinant in DDR and BER. Additionally, DNA damage levels were measured to examine the overall damage levels. No impact of ageing on the investigated endpoints in liver tissue were found. However, animal sex seems to be a significant impact factor, as evident by sex-dependent alterations in all endpoints investigated. Moreover, our results revealed interrelationships between the investigated endpoints indicative for the synergetic mode of action of the cellular DNA integrity maintaining machinery.
Author summary <br /> The use of orally inhaled drugs for treating lung diseases is appealing since they have the potential for lung selectivity, i.e. high exposure at the site of action -the lung- without excessive side effects. However, the degree of lung selectivity depends on a large number of factors, including physiochemical properties of drug molecules, patient disease state, and inhalation devices. To predict the impact of these factors on drug exposure and thereby to understand the characteristics of an optimal drug for inhalation, we develop a predictive mathematical framework (a "pharmacokinetic model"). In contrast to previous approaches, our model allows combining knowledge from different sources appropriately and its predictions were able to adequately predict different sets of clinical data. Finally, we compare the impact of different factors and find that the most important factors are the size of the inhaled particles, the affinity of the drug to the lung tissue, as well as the rate of drug dissolution in the lung. In contrast to the common belief, the solubility of a drug in the lining fluids is not found to be relevant. These findings are important to understand how inhaled drugs should be designed to achieve best treatment results in patients. <br /> The fate of orally inhaled drugs is determined by pulmonary pharmacokinetic processes such as particle deposition, pulmonary drug dissolution, and mucociliary clearance. Even though each single process has been systematically investigated, a quantitative understanding on the interaction of processes remains limited and therefore identifying optimal drug and formulation characteristics for orally inhaled drugs is still challenging. To investigate this complex interplay, the pulmonary processes can be integrated into mathematical models. However, existing modeling attempts considerably simplify these processes or are not systematically evaluated against (clinical) data. In this work, we developed a mathematical framework based on physiologically-structured population equations to integrate all relevant pulmonary processes mechanistically. A tailored numerical resolution strategy was chosen and the mechanistic model was evaluated systematically against data from different clinical studies. Without adapting the mechanistic model or estimating kinetic parameters based on individual study data, the developed model was able to predict simultaneously (i) lung retention profiles of inhaled insoluble particles, (ii) particle size-dependent pharmacokinetics of inhaled monodisperse particles, (iii) pharmacokinetic differences between inhaled fluticasone propionate and budesonide, as well as (iv) pharmacokinetic differences between healthy volunteers and asthmatic patients. Finally, to identify the most impactful optimization criteria for orally inhaled drugs, the developed mechanistic model was applied to investigate the impact of input parameters on both the pulmonary and systemic exposure. Interestingly, the solubility of the inhaled drug did not have any relevant impact on the local and systemic pharmacokinetics. Instead, the pulmonary dissolution rate, the particle size, the tissue affinity, and the systemic clearance were the most impactful potential optimization parameters. In the future, the developed prediction framework should be considered a powerful tool for identifying optimal drug and formulation characteristics.
Author summary <br /> Switching between local and global attention is a general strategy in human information processing. We investigate whether this strategy is a viable approach to model sequences of fixations generated by a human observer in a free viewing task with natural scenes. Variants of the basic model are used to predict the experimental data based on Bayesian inference. Results indicate a high predictive power for both aggregated data and individual differences across observers. The combination of a novel model with state-of-the-art Bayesian methods lends support to our two-state model using local and global internal attention states for controlling eye movements. <br /> Understanding the decision process underlying gaze control is an important question in cognitive neuroscience with applications in diverse fields ranging from psychology to computer vision. The decision for choosing an upcoming saccade target can be framed as a selection process between two states: Should the observer further inspect the information near the current gaze position (local attention) or continue with exploration of other patches of the given scene (global attention)? Here we propose and investigate a mathematical model motivated by switching between these two attentional states during scene viewing. The model is derived from a minimal set of assumptions that generates realistic eye movement behavior. We implemented a Bayesian approach for model parameter inference based on the model's likelihood function. In order to simplify the inference, we applied data augmentation methods that allowed the use of conjugate priors and the construction of an efficient Gibbs sampler. This approach turned out to be numerically efficient and permitted fitting interindividual differences in saccade statistics. Thus, the main contribution of our modeling approach is two-fold; first, we propose a new model for saccade generation in scene viewing. Second, we demonstrate the use of novel methods from Bayesian inference in the field of scan path modeling.
The steady increase of ground-motion data not only allows new possibilities but also comes with new challenges in the development of ground-motion models (GMMs). Data classification techniques (e.g., cluster analysis) do not only produce deterministic classifications but also probabilistic classifications (e.g., probabilities for each datum to belong to a given class or cluster). One challenge is the integration of such continuous classification in regressions for GMM development such as the widely used mixed-effects model. We address this issue by introducing an extension of the mixed-effects model to incorporate data weighting. The parameter estimation of the mixed-effects model, that is, fixed-effects coefficients of the GMMs and the random-effects variances, are based on the weighted likelihood function, which also provides analytic uncertainty estimates. The data weighting permits for earthquake classification beyond the classical, expert-driven, binary classification based, for example, on event depth, distance to trench, style of faulting, and fault dip angle. We apply Angular Classification with Expectation-maximization, an algorithm to identify clusters of nodal planes from focal mechanisms to differentiate between, for example, interface- and intraslab-type events. Classification is continuous, that is, no event belongs completely to one class, which is taken into account in the ground-motion modeling. The theoretical framework described in this article allows for a fully automatic calibration of ground-motion models using large databases with automated classification and processing of earthquake and ground-motion data. As an example, we developed a GMM on the basis of the GMM by Montalva et al. (2017) with data from the strong-motion flat file of Bastias and Montalva (2016) with similar to 2400 records from 319 events in the Chilean subduction zone. Our GMM with the data-driven classification is comparable to the expert-classification-based model. Furthermore, the model shows temporal variations of the between-event residuals before and after large earthquakes in the region.
Many Android applications embed webpages via WebView components and execute JavaScript code within Android. Hybrid applications leverage dedicated APIs to load a resource and render it in a WebView. Furthermore, Android objects can be shared with the JavaScript world. However, bridging the interfaces of the Android and JavaScript world might also incur severe security threats: Potentially untrusted webpages and their JavaScript might interfere with the Android environment and its access to native features.
No general analysis is currently available to assess the implications of such hybrid apps bridging the two worlds. To understand the semantics and effects of hybrid apps, we perform a large-scale study on the usage of the hybridization APIs in the wild. We analyze and categorize the parameters to hybridization APIs for 7,500 randomly selected and the 196 most popular applications from the Google Playstore as well as 1000 malware samples. Our results advance the general understanding of hybrid applications, as well as implications for potential program analyses, and the current security situation: We discovered thousands of flows of sensitive data from Android to JavaScript, the vast majority of which could flow to potentially untrustworthy code. Our analysis identified numerous web pages embedding vulnerabilities, which we exemplarily exploited. Additionally, we discovered a multitude of applications in which potentially untrusted JavaScript code may interfere with (trusted) Android objects, both in benign and malign applications.
Although the use of stable transformation technology has led to great insight into gene function, its application in high-throughput studies remains arduous. Agro-infiltration have been widely used in species such as Nicotiana benthamiana for the rapid detection of gene expression and protein interaction analysis, but this technique does not work efficiently in other plant species, including Arabidopsis thaliana. As an efficient high-throughput transient expression system is currently lacking in the model plant species A. thaliana, we developed a method that is characterized by high efficiency, reproducibility, and suitability for transient expression of a variety of functional proteins in A. thaliana and 7 other plant species, including Brassica oleracea, Capsella rubella, Thellungiella salsuginea, Thellungiella halophila, Solanum tuberosum, Capsicum annuum, and N. benthamiana. Efficiency of this method was independently verified in three independent research facilities, pointing to the robustness of this technique. Furthermore, in addition to demonstrating the utility of this technique in a range of species, we also present a case study employing this method to assess protein-protein interactions in the sucrose biosynthesis pathway in Arabidopsis.
We discuss an efficient Hierarchical Effective Mode (HEM) representation of a high-dimensional harmonic oscillator bath, which describes phonon-driven vibrational relaxation of an adsorbate-surface system, namely, deuterium adsorbed on Si(100). Starting from the original Hamiltonian of the adsorbate-surface system, the HEM representation is constructed via iterative orthogonal transformations, which are efficiently implemented with Householder matrices. The detailed description of the HEM representation and its construction are given in the second quantization representation. The hierarchical nature of this representation allows access to the exact quantum dynamics of the adsorbate-surface system over finite time intervals, controllable via the truncation order of the hierarchy. To study the convergence properties of the effective mode representation, we solve the time-dependent Schrodinger equation of the truncated system-bath HEM Hamiltonian, with the help of the multilayer extension of the Multiconfigurational Time-Dependent Hartree (ML-MCTDH) method. The results of the HEM representation are compared with those obtained with a quantum-mechanical tier-model. The convergence of the HEM representation with respect to the truncation order of the hierarchy is discussed for different initial conditions of the adsorbate-surface system. The combination of the HEM representation with the ML-MCTDH method provides information on the time evolution of the system (adsorbate) and multiple effective modes of the bath (surface). This permits insight into mechanisms of vibration-phonon coupling of the adsorbate-surface system, as well as inter-mode couplings of the effective bath.
Supramolecular polymers or fibers are non-covalent assemblies of unimeric building blocks connected by secondary interactions such as hydrogen bonds or pi-pi interactions. Such structures hold enormous potential in the development of future materials, as their non-covalent nature makes them highly modular and adaptive. Within this review we aim to provide a broad overview over the area of linear supramolecular polymers including the different mechanisms of their polymerization as well as methods essential for their characterization. The different non-covalent interactions able to form supramolecular polymers are discussed, and key examples for each species are shown. Particular emphasis is laid on the development of living supramolecular polymerization able to produce fibers with a controlled length and low length dispersity, and even enable the production of supramolecular block copolymers. Another important and very recent field is the development of out-of-equilibrium supramolecular polymers, where the polymerization process can be temporally controlled enabling access to highly adaptive materials.
A ground motion logic tree for seismic hazard analysis in the stable cratonic region of Europe
(2020)
Regions of low seismicity present a particular challenge for probabilistic seismic hazard analysis when identifying suitable ground motion models (GMMs) and quantifying their epistemic uncertainty. The 2020 European Seismic Hazard Model adopts a scaled backbone approach to characterise this uncertainty for shallow seismicity in Europe, incorporating region-to-region source and attenuation variability based on European strong motion data. This approach, however, may not be suited to stable cratonic region of northeastern Europe (encompassing Finland, Sweden and the Baltic countries), where exploration of various global geophysical datasets reveals that its crustal properties are distinctly different from the rest of Europe, and are instead more closely represented by those of the Central and Eastern United States. Building upon the suite of models developed by the recent NGA East project, we construct a new scaled backbone ground motion model and calibrate its corresponding epistemic uncertainties. The resulting logic tree is shown to provide comparable hazard outcomes to the epistemic uncertainty modelling strategy adopted for the Eastern United States, despite the different approaches taken. Comparison with previous GMM selections for northeastern Europe, however, highlights key differences in short period accelerations resulting from new assumptions regarding the characteristics of the reference rock and its influence on site amplification.
Plants located adjacent to agricultural fields are important for maintaining biodiversity in semi-natural landscapes. To avoid undesired impacts on these plants due to herbicide application on the arable fields, regulatory risk assessments are conducted prior to registration to ensure proposed uses of plant protection products do not present an unacceptable risk. The current risk assessment approach for these non-target terrestrial plants (NTTPs) examines impacts at the individual-level as a surrogate approach for protecting the plant community due to the inherent difficulties of directly assessing population or community level impacts. However, modelling approaches are suitable higher tier tools to upscale individual-level effects to community level. IBC-grass is a sophisticated plant community model, which has already been applied in several studies. However, as it is a console application software, it was not deemed sufficiently user-friendly for risk managers and assessors to be conveniently operated without prior expertise in ecological models. Here, we present a user-friendly and open source graphical user interface (GUI) for the application of IBC-grass in regulatory herbicide risk assessment. It facilitates the use of the plant community model for predicting long-term impacts of herbicide applications on NTTP communities. The GUI offers two options to integrate herbicide impacts: (1) dose responses based on current standard experiments (acc. to testing guidelines) and (2) based on specific effect intensities. Both options represent suitable higher tier options for future risk assessments of NTTPs as well as for research on the ecological relevance of effects.
The termprocess modelis widely used, but rarely agreed upon. This paper proposes a framework for characterizing and building cognitive process models. Process models model not only inputs and outputs but also model the ongoing information transformations at a given level of abstraction. We argue that the following dimensions characterize process models: They have a scope that includes different levels of abstraction. They specify a hypothesized mental information transformation. They make predictions not only for the behavior of interest but also for processes. The models' predictions for the processes can be derived from the input, without reverse inference from the output data. Moreover, the presumed information transformation steps are not contradicting current knowledge of human cognitive capacities. Lastly, process models require a conceptual scope specifying levels of abstraction for the information entering the mind, the proposed mental events, and the behavior of interest. This framework can be used for refining models before testing them or after testing them empirically, and it does not rely on specific modeling paradigms. It can be a guideline for developing cognitive process models. Moreover, the framework can advance currently unresolved debates about which models belong to the category of process models.
Biogenic greenhouse gas emissions, e.g., of methane (CH4) and carbon dioxide (CO2) from inland waters, contribute substantially to global warming. In aquatic systems, dissolved greenhouse gases are highly heterogeneous in both space and time. To better understand the biological and physical processes that affect sources and sinks of both CH4 and CO2, their dissolved concentrations need to be measured with high spatial and temporal resolution. To achieve this goal, we developed the Fast-Response Automated Gas Equilibrator (FaRAGE) for real-time in situ measurement of dissolved CH4 and CO2 concentrations at the water surface and in the water column. FaRAGE can achieve an exceptionally short response time (t(95%) = 12 s when including the response time of the gas analyzer) while retaining an equilibration ratio of 62.6% and a measurement accuracy of 0.5% for CH4. A similar performance was observed for dissolved CO2 (t(95%) = 10 s, equilibration ratio 67.1 %). An equilibration ratio as high as 91.8% can be reached at the cost of a slightly increased response time (16 s). The FaRAGE is capable of continuously measuring dissolved CO2 and CH4 concentrations in the nM-to-submM (10(-9)-10(-3) mol L-1) range with a detection limit of subnM (10(-10) mol L-1), when coupling with a cavity ring-down greenhouse gas analyzer (Picarro GasScouter). FaRAGE allows for the possibility of mapping dissolved concentration in a "quasi" three-dimensional manner in lakes and provides an inexpensive alternative to other commercial gas equilibrators. It is simple to operate and suitable for continuous monitoring with a strong tolerance for suspended particles. While the FaRAGE is developed for inland waters, it can be also applied to ocean waters by tuning the gas-water mixing ratio. The FaRAGE is easily adapted to suit other gas analyzers expanding the range of potential applications, including nitrous oxide and isotopic composition of the gases.
Cyber-physical systems (CPS) have shaped the discussion about Industry 4.0 (I4.0) for some time. To ensure the competitiveness of manufacturing enterprises the vision for the future figures out cyber-physical production systems (CPPS) as a core component of a modern factory. Adaptability and coping with complexity are (among others) potentials of this new generation of production management. The successful transformation of this theoretical construct into practical implementation can only take place with regard to the conditions characterizing the context of a factory. The subject of this contribution is a concept that takes up the brownfield character and describes a solution for extending existing (legacy) systems with CPS capabilities.
There is an increasing interest in fusing data from heterogeneous sources. Combining data sources increases the utility of existing datasets, generating new information and creating services of higher quality. A central issue in working with heterogeneous sources is data migration: In order to share and process data in different engines, resource intensive and complex movements and transformations between computing engines, services, and stores are necessary.
Muses is a distributed, high-performance data migration engine that is able to interconnect distributed data stores by forwarding, transforming, repartitioning, or broadcasting data among distributed engines' instances in a resource-, cost-, and performance-adaptive manner. As such, it performs seamless information sharing across all participating resources in a standard, modular manner. We show an overall improvement of 30 % for pipelining jobs across multiple engines, even when we count the overhead of Muses in the execution time. This performance gain implies that Muses can be used to optimise large pipelines that leverage multiple engines.
We study those nonlinear partial differential equations which appear as Euler-Lagrange equations of variational problems. On defining weak boundary values of solutions to such equations we initiate the theory of Lagrangian boundary value problems in spaces of appropriate smoothness. We also analyse if the concept of mapping degree of current importance applies to Lagrangian problems.
Compound natural hazards likeEl Ninoevents cause high damage to society, which to manage requires reliable risk assessments. Damage modelling is a prerequisite for quantitative risk estimations, yet many procedures still rely on expert knowledge, and empirical studies investigating damage from compound natural hazards hardly exist. A nationwide building survey in Peru after theEl Ninoevent 2017 - which caused intense rainfall, ponding water, flash floods and landslides - enables us to apply data-mining methods for statistical groundwork, using explanatory features generated from remote sensing products and open data. We separate regions of different dominant characteristics through unsupervised clustering, and investigate feature importance rankings for classifying damage via supervised machine learning. Besides the expected effect of precipitation, the classification algorithms select the topographic wetness index as most important feature, especially in low elevation areas. The slope length and steepness factor ranks high for mountains and canyons. Partial dependence plots further hint at amplified vulnerability in rural areas. An example of an empirical damage probability map, developed with a random forest model, is provided to demonstrate the technical feasibility.
Children's participation in legal proceedings affecting them personally has been gaining importance. So far, a primary research concern has been how children experience their participation in court proceedings. However, little is known about the child's voice itself: Are children able to clearly express their wishes, and if so, what do they say in child protection cases? In this study, we extracted information about children's statements from court file data of 220 child protection cases in Germany. We found 182 children were asked about their wishes. The majority of the statements found came either from reports of the guardians ad litem or from judicial records of the child hearings. Using content analysis, three main aspects of the statements were extracted: wishes concerning main place of residence, wishes about whom to have or not contact with, and children granting decision-making authority to someone else. Children's main focus was on their parents, but others (e.g., relatives and foster care providers) were also mentioned. Intercoder agreement was substantial. Making sure that child hearings are as informative as possible is in the child's best interest. Therefore, the categories developed herein might help professionals to ask questions more precisely relevant to the child.