Measuring Behavior using Motion Capture

Motion capture systems, using optical, magnetic or mechanical sensors are now widely used to record\ud human motion. Motion capture provides us with precise measurements of human motion at a very high\ud recording frequency and accuracy, resulting in a massive amount of movement data on several joints of the\ud body or markers of the face. But how do we make sure that we record the right things? And how can we\ud correctly interpret the recorded data?\ud In this multi-disciplinary symposium, speakers from the field of biomechanics, computer animation, human\ud computer interaction and behavior science come together to discus their methods to both record motion and\ud to extract useful properties from the data. In these fields, the construction of human movement models from\ud motion capture data is the focal point, although the application of such models differs per field. Such\ud models can be used to generate and evaluate highly adaptable and believable animation on virtual\ud characters in computer animation, to explore the details of gesture interaction in Human Computer\ud Interaction applications, to identify patterns related to affective states or to find biomechanical properties of\ud human movement

Vulnerability in acquisition, language impairments in Dutch: Creating a VALID data archive

The VALID Data Archive is an open multimedia data archive (under construction) with data from speakers suffering from language impairments. We report on a pilot project in the CLARIN-NL framework in which five data resources were curated. For all data sets concerned, written informed consent from the participants or their caretakers has been obtained. All materials were anonymized. The audio files were converted into wav (linear PCM) files and the transcriptions into CHAT or ELAN format. Research data that consisted of test, SPSS and Excel files were documented and converted into CSV files. All data sets obtained appropriate CMDI metadata files. A new CMDI metadata profile for this type of data resources was established and care was taken that ISOcat metadata categories were used to optimize interoperability. After curation all data are deposited at the Max Planck Institute for Psycholinguistics Nijmegen where persistent identifiers are linked to all resources. The content of the transcriptions in CHAT and plain text format can be searched with the TROVA search engin

Architectural plasticity of human BRCA2-RAD51 complexes in DNA break repair

The tumor suppressor BRCA2 is a large multifunctional protein mutated in 50-60% of familial breast cancers. BRCA2 interacts with many partners and includes multiple regions with potentially disordered structure. In homology directed DNA repair BRCA2 delivers RAD51 to DNA resulting in removal of RPA and assembly of a RAD51 nucleoprotein filame

Dutch and German 3-year-olds’ representations of voicing alternations

The voicing contrast is neutralised syllable and word finally in Dutch and German, leading to alternations within the morphological paradigm (e.g. Dutch ‘bed(s)’, be[t] be[d]en, German ‘dog(s)’, Hun[t]-Hun[d]e). Despite structural similarity, language-specific morphological, phonological and lexical properties impact on the distribution of this alternation in the two languages. Previous acquisition research has focused on one language only, predominantly focusing on children’s production accuracy, concluding that alternations are not acquired until late in the acquisition process in either language. This paper adapts a perceptual method to investigate how voicing alternations are represented in the mental lexicon of Dutch and German 3-year-olds. Sensitivity to mispronunciations of voicing word-medially in plural forms was measured using a visual fixation procedure. Dutch children exhibited evidence of overgeneralising the voicing alternation, whereas German children consistently preferred the correct pronunciation to mispronunciations. Results indicate that the acquisition of voicing alternations is influenced by language-specific factors beyond the alternation itself

Discovery of a small-molecule HIV-1 integrase inhibitor-binding site

Herein, we report the identification of a unique HIV-1 integrase (IN) inhibitor-binding site using photoaffinity labeling and mass spectrometric analysis. We chemically incorporated a photo-activatable benzophenone moiety into a series of coumarin-containing IN inhibitors. A representative of this series was covalently photo-crosslinked with the IN core domain and subjected to HPLC purification. Fractions were subsequently analyzed by using MALDI-MS and electrospray ionization (ESI)-MS to identify photo-crosslinked products. In this fashion, a single binding site for an inhibitor located within the tryptic peptide 128AACWWAGIK136 was identified. Site-directed mutagenesis followed by in vitro inhibition assays resulted in the identification of two specific amino acid residues, C130 and W132, in which substitutions resulted in a marked resistance to the IN inhibitors. Docking studies suggested a specific disruption in functional oligomeric IN complex formation. The combined approach of photo-affinity labeling/MS analysis with site-directed mutagenesis/molecular modeling is a powerful approach for elucidating inhibitor-binding sites of proteins at the atomic level. This approach is especially important for the study of proteins that are not amenable to traditional x-ray crystallography and NMR techniques. This type of structural information can help illuminate processes of inhibitor resistance and thereby facilitate the design of more potent second-generation inhibitors

Vulnerability in Acquisition, Language Impairments in Dutch: Creating a VALID Data Archive

Vulnerability in Acquisition, Language Impairments in Dutch: Creating a VALID Data Archive Klatter, J.; van Hout, R.; van den Heuvel, H.; Fikkert, P.; Baker, A.E.; de Jong, J.; Wijnen, F.; Sanders, E.; Trilsbeek, P. General rights It is not permitted to download or to forward/distribute the text or part of it without the consent of the author(s) and/or copyright holder(s), other than for strictly personal, individual use, unless the work is under an open content license (like Creative Commons). Disclaimer/Complaints regulations If you believe that digital publication of certain material infringes any of your rights or (privacy) interests, please let the Library know, stating your reasons. In case of a legitimate complaint, the Library will make the material inaccessible and/or remove it from the website. Please Ask the Library: https://uba.uva.nl/en/contact, or a letter to: Library of the University of Amsterdam, Secretariat, Singel 425, 1012 WP Amsterdam, The Netherlands. You will be contacted as soon as possible. Abstract The VALID Data Archive is an open multimedia data archive (under construction) with data from speakers suffering from language impairments. We report on a pilot project in the CLARIN-NL framework in which five data resources were curated. For all data sets concerned, written informed consent from the participants or their caretakers has been obtained. All materials were anonymized. The audio files were converted into wav (linear PCM) files and the transcriptions into CHAT or ELAN format. Research data that consisted of test, SPSS and Excel files were documented and converted into CSV files. All data sets obtained appropriate CMDI metadata files. A new CMDI metadata profile for this type of data resources was established and care was taken that ISOcat metadata categories were used to optimize interoperability. After curation all data are deposited at the Max Planck Institute for Psycholinguistics Nijmegen where persistent identifiers are linked to all resources. The content of the transcriptions in CHAT and plain text format can be searched with the TROVA search engine

Caffeine suppresses homologous recombination through interference with RAD51-mediated joint molecule formation

Caffeine is a widely used inhibitor of the protein kinases that play a central role in the DNA damage response. We used chemical inhibitors and genetically deficient mouse embryonic stem cell lines to study the role of DNA damage response in stable integration of the transfected DNA and found that caffeine rapidly, efficiently and reversibly inhibited homologous integration of the transfected DNA as measured by several homologous recombination-mediated gene-targeting assays. Biochemical and structural biology experiments revealed that caffeine interfered with a pivotal step in homologous recombination, homologous joint molecule formation, through increasing interactions of the RAD51 nucleoprotein filament with non-homologous DNA. Our results suggest that recombination pathways dependent on extensive homology search are caffeine-sensitive and stress the importance of considering direct checkpoint-independent mechanisms in the interpretation of the effects of caffeine on DNA repair

Effect of the BRCA2 CTRD domain on RAD51 filaments analyzed by an ensemble of single molecule techniques

Homologous recombination is essential for the preservation of genome stability, thereby preventing cancer. The recombination protein RAD51 drives DNA strand exchange, which requires the assembly, rearrangement and disassembly of a RAD51 filament on DNA, coupled to ATP binding and hydrolysis. This process is facilitated and controlled by recombination mediators and accessory factors. Here, we have employed a range of single molecule techniques to determine the influence of the C-terminal RAD51 interaction domain (CTRD) of the breast cancer tumor suppressor BRCA2 on intrinsic aspects of RAD51-DNA interactions. We show that at high concentration the CTRD entangles RAD51 filaments and reduces RAD51 filament formation in a concentration dependent manner. It does not affect the rate of filament disassembly measured as the loss of fluorescent signal due to intrinsic RAD51 protein dissociation from double-stranded DNA (dsDNA). We conclude that, outside the context of the full-length protein, the CTRD does not reduce RAD51 dissociation kinetics, but instead hinders filament formation on dsDNA. The CTRDs mode of action is most likely sequestration of multiple RAD51 molecules thereby rendering them inactive for filament formation on dsDNA

LEDGF/p75-Independent HIV-1 Replication Demonstrates a Role for HRP-2 and Remains Sensitive to Inhibition by LEDGINs

Lens epithelium–derived growth factor (LEDGF/p75) is a cellular cofactor of HIV-1 integrase (IN) that interacts with IN through its IN binding domain (IBD) and tethers the viral pre-integration complex to the host cell chromatin. Here we report the generation of a human somatic LEDGF/p75 knockout cell line that allows the study of spreading HIV-1 infection in the absence of LEDGF/p75. By homologous recombination the exons encoding the LEDGF/p75 IBD (exons 11 to 14) were knocked out. In the absence of LEDGF/p75 replication of laboratory HIV-1 strains was severely delayed while clinical HIV-1 isolates were replication-defective. The residual replication was predominantly mediated by the Hepatoma-derived growth factor related protein 2 (HRP-2), the only cellular protein besides LEDGF/p75 that contains an IBD. Importantly, the recently described IN-LEDGF/p75 inhibitors (LEDGINs) remained active even in the absence of LEDGF/p75 by blocking the interaction with the IBD of HRP-2. These results further support the potential of LEDGINs as allosteric integrase inhibitors

Quantifying sources of variability in infancy research using the infant-directed-speech preference

Psychological scientists have become increasingly concerned with issues related to methodology and replicability, and infancy researchers in particular face specific challenges related to replicability: For example, high-powered studies are difficult to conduct, testing conditions vary across labs, and different labs have access to different infant populations. Addressing these concerns, we report on a large-scale, multisite study aimed at (a) assessing the overall replicability of a single theoretically important phenomenon and (b) examining methodological, cultural, and developmental moderators. We focus on infants’ preference for infant-directed speech (IDS) over adult-directed speech (ADS). Stimuli of mothers speaking to their infants and to an adult in North American English were created using seminaturalistic laboratory-based audio recordings. Infants’ relative preference for IDS and ADS was assessed across 67 laboratories in North America, Europe, Australia, and Asia using the three common methods for measuring infants’ discrimination (head-turn preference, central fixation, and eye tracking). The overall meta-analytic effect size (Cohen’s d) was 0.35, 95% confidence interval = [0.29, 0.42], which was reliably above zero but smaller than the meta-analytic mean computed from previous literature (0.67). The IDS preference was significantly stronger in older children, in those children for whom the stimuli matched their native language and dialect, and in data from labs using the head-turn preference procedure. Together, these findings replicate the IDS preference but suggest that its magnitude is modulated by development, native-language experience, and testing procedure. (This project has received funding from the European Union’s Horizon 2020 research and innovation programme under the Marie Skłodowska-Curie grant agreement No 798658.