368 research outputs found
Non-monotonic dynamic correlations beneath the surface of glass-forming liquids
Collective motion over increasing length scales is a signature of the
vitrification process of liquids. We demonstrate the emergence of distinct
static and dynamic length scales probed near the free surface in fully
equilibrated glass-forming liquid films, and their connection to the bulk
properties of the system. In contrast to a monotonically growing static
correlation length, the dynamic correlation length that measures the extent of
surface-dynamics acceleration into the bulk, displays a striking non-monotonic
temperature evolution that is robust also against changes in detailed
interatomic interaction. The maximum of dynamic correlations defines a
cross-over temperature that we show to agree with a morphological change
of cooperative rearrangement regions (CRR) of fast particles in the bulk
liquids. The cross-over occurs at a temperature larger than the critical
temperature Tc of mode-coupling theory (MCT). We link it to the point where
fast-particle motion decouples from structural relaxation that can be defined
rigorously within a recent extension of MCT, the stochastic -relaxation
theory (SBR)
The formation of acetylcholine receptor clusters visualized with quantum dots
Background: Motor innervation of skeletal muscle leads to the assembly of acetylcholine receptor (AChR) clusters in the postsynaptic membrane at the vertebrate neuromuscular junction (NMJ). Synaptic AChR aggregation, according to the diffusion-mediated trapping hypothesis, involves the establishment of a postsynaptic scaffold that "traps" freely diffusing receptors into forming high-density clusters. Although this hypothesis is widely cited to explain the formation of postsynaptic AChR clusters, direct evidence at molecular level is lacking. Results: Using quantum dots (QDs) and live cell imaging, we provide new measurements supporting the diffusion-trap hypothesis as applied to AChR cluster formation. Consistent with published works, experiments on cultured Xenopus myotomal muscle cells revealed that AChRs at clusters that formed spontaneously (pre-patterned clusters, also called hot spots) and at those induced by nerve-innervation or by growth factor-coated latex beads were very stable whereas diffuse receptors outside these regions were mobile. Moreover, despite the restriction of AChR movement at sites of synaptogenic stimulation, individual receptors away from these domains continued to exhibit free diffusion, indicating that AChR clustering at NMJ does not involve an active attraction of receptors but is passive and diffusion-driven. Conclusion: Single-molecular tracking using QDs has provided direct evidence that the clustering of AChRs in muscle cells in response to synaptogenic stimuli is achieved by two distinct cellular processes: the Brownian motion of receptors in the membrane and their trapping and immobilization at the synaptic specialization. This study also provides a clearer picture of the "trap" that it is not a uniformly sticky area but consists of discrete foci at which AChRs are immobilized
Crosslinking-induced endocytosis of acetylcholine receptors by quantum dots
In a majority of patients with myasthenia gravis (MG), anti-acetylcholine receptor (AChR) antibodies target postsynaptic AChR clusters and thus compromise the membrane integrity of neuromuscular junctions (NMJs) and lead to muscle weakness. Antibody-induced endocytosis of AChRs in the postsynaptic membrane represents the initial step in the pathogenesis of MG; however, the molecular mechanisms underlying AChR endocytosis remain largely unknown. Here, we developed an approach to mimic the pathogenic antibodies for inducing the crosslinking and internalization of AChRs from the postsynaptic membrane. Using biotin-Ī±-bungarotoxin and quantum dot (QD)-streptavidin, cell-surface and internalized AChRs could be readily distinguished by comparing the size, fluorescence intensity, trajectory, and subcellular localization of the QD signals. QD-induced AChR endocytosis was mediated by clathrin-dependent and caveolin-independent mechanisms, and the trafficking of internalized AChRs in the early endosomes required the integrity of microtubule structures. Furthermore, activation of the agrin/MuSK (muscle-specific kinase) signaling pathway strongly suppressed QD-induced internalization of AChRs. Lastly, QD-induced AChR crosslinking potentiated the dispersal of aneural AChR clusters upon synaptic induction. Taken together, our results identify a novel approach to study the mechanisms of AChR trafficking upon receptor crosslinking and endocytosis, and demonstrate that agrin-MuSK signaling pathways protect against crosslinking-induced endocytosis of AChRs. Ā© 2014 Lee et al.published_or_final_versio
Reliability and accuracy of interview data in non-smoking female lung cancer case-control study
<p>Abstract</p> <p>Background</p> <p>Valid interview data is critical to the final results of the study. The purpose of this study was to investigate the reliability of epidemiological data obtained in non-smoking female lung cancer case-control study in China.</p> <p>Methods</p> <p>Fifty-six pairs of cases and controls, 10% percent of all the collected subjects were re-interviewed by three interviewers who underwent identical standardized training. A limited number of questions included in the original survey were asked again, the responses from the re-interview were compared with the original interview. Kappa was calculated by negative rates of agreement, positive rates of agreement and total rates of agreement to the accordance degree between the two interviews.</p> <p>Results</p> <p>The Kappa values were all more than 0.5 in all the studied indexes. The Kappa values descended from 0.92 in family history of cancer to 0.56 in oral contraception use. Errors in collecting and classifying data did occur, and were especially common for complicated clinical events, such as a drug exposure occurring many years before.</p> <p>Conclusion</p> <p>We identified four sources of this variability, three in collecting the data, and one in coding. As a result of these findings, strategies are proposed for improving the quality of interview data obtained in epidemiological research. Before finding a good solution, the strategy of data collecting and coding should be simple and easy to inspect.</p
Is Silent External HumanāMachine Interface (eHMI) Enough? A Passenger-Centric Study on Effective eHMI for Autonomous Personal Mobility Vehicles in the Field
Density functional quantum mechanical research yield a comprehensive theoretical approach on the selected organic molecule of 9,9-dihydroxynanoic acid. The DFT approach is implemented to optimise the molecular structure. The geometrical parameters of molecule were calculated. The vibrational spectrum studies were done with FT-IR and FT-Raman and their results were investigated. VEDA software is utilised to simulate PED for the basic vibrational frequencies in order to find all the vibration modes. UVāVis analysis is performed for the gaseous phase and on solvent phases such as water, ethanol, ethyl ethanoate, acetone, and DMSO by TD-DFT-B3LYP with 6-311++G (d,p), and band gap energies are calculated. FMO investigations reported analysing the compound energy gap, softness, hardness, and electrophilicity index in gaseous phase along with a variety solvent phase. To further understand the molecule\u27s reactive areas, Mulliken atomic charge evaluation, Fukui functions, and dual descriptors were conceptually investigated. The electro static MEP map of the compound in distinct solvent phases is provided in order to comprehend the molecular shape, size, and reactive region. The molecule\u27s hyperpolarizability is observed to be 201.8 a.u for gas, 146.6 a.u for acetone, 138.9 a.u for DMSO, 136.3 a.u for water, and 169.8 a.u for ethyl ethanoate, will supports the molecule is good NLO material. The donor acceptor interaction has been explored so as to explain the intramolecular hyper conjugative interaction and stability. To understand the topology Multiwfn analysis like ELF, LOL and ALIE were done. The E.coli proteins are downloaded from the PDB database and fictitiously docked with our selected ligand molecule using Auto Dock software to determine hydrogen bonding and binding energy
Is Silent External HumanāMachine Interface (eHMI) Enough? A Passenger-Centric Study on Effective eHMI for Autonomous Personal Mobility Vehicles in the Field
Autonomous personal mobility vehicle (APMV) is a miniaturized autonomous vehicle designed for short-distance mobility to everyone. Due to its open design, APMVās passengers are exposed to communications between the external human-machine interface (eHMI) on APMV and pedestrians. Therefore, effective eHMI designs for APMV need to consider potential impacts of APMV-pedestrian interactions on passengersā subjective feelings. This study from the perspective of APMV passengers discussed three eHMI designs: (1) graphical user interface (GUI)-based eHMI with text message (eHMI-T), (2) multimodal user interface (MUI)-based eHMI with neutral voice (eHMI-NV), and (3) MUI-based eHMI with affective voice (eHMI-AV). In a riding field experiment (Nā=ā24), eHMI-T made passengers feel awkward during the āsilent timeā when eHMI-T conveyed information exclusively to pedestrians, not passengers. MUI-based eHMIs with voice cues showed advantages, with eHMI-NV excelling in pragmatic quality and eHMI-AV in hedonic quality. Considering passengersā personalities and genders in APMV eHMI design is also highlighted
Is Silent eHMI Enough? A Passenger-Centric Study on Effective eHMI for Autonomous Personal Mobility Vehicles in the Field
Autonomous personal mobility vehicle (APMV) is a miniaturized autonomous
vehicle that is used in pedestrian-rich environments. In addition, the open
bodywork design of APMVs exposes passengers to the communication between the
eHMI deployed on APMVs and pedestrians. Therefore, to ensure an optimal
passenger experience, eHMI designs for APMVs must consider the potential impact
of APMV-pedestrian communications on passengers' psychological feelings. This
study discussed three external human-machine interface (eHMI) designs, i.e.,
eHMI with text message (eHMI-T), eHMI with neutral voice (eHMI-NV) and eHMI
with affective voice (eHMI-AV), from the perspective of APMV passengers in the
communication between APMV and pedestrians. In the riding experiment, we found
that eHMI-T may be less suitable for APMVs. This conclusion was drawn based on
passengers' feedback, as they expressed feeling awkward during the ``silent
period'' because the eHMI-T conveyed information only to pedestrians but not to
passengers. Additionally, the affective voice cues on eHMI improved overall
user experience of passengers, leading to higher ratings for both pragmatic and
hedonic quality. The study also highlights the necessity of considering
passengers' personalities when designing eHMI for APMVs to enhance their
experience
Nonmonotonic Dynamical Correlations beneath the Surface of Glass-Forming Liquids
Collective motion over increasing length scales is a signature of the vitrification process of liquids. We demonstrate how distinct static and dynamic length scales govern the dynamics of vitrifying films. In contrast to a monotonically growing static correlation length, the dynamical correlation length that measures the extent of surface-dynamics acceleration into the bulk displays a striking nonmonotonic temperature evolution that is robust also against changes in detailed interatomic interaction. This nonmonotonic change defines a crossover temperature T* that is distinct from the critical temperature Tc of mode-coupling theory. We connect this nonmonotonic change to a morphological change of cooperative rearrangement regions of fast particles, and to the point where the decoupling of fast-particle motion from the bulk relaxation is most sensitive to fluctuations. We propose a rigorous definition of this new crossover temperature T* within a recent extension of mode-coupling theory, the stochastic beta-relaxation theory
COPEN: Probing Conceptual Knowledge in Pre-trained Language Models
Conceptual knowledge is fundamental to human cognition and knowledge bases.
However, existing knowledge probing works only focus on evaluating factual
knowledge of pre-trained language models (PLMs) and ignore conceptual
knowledge. Since conceptual knowledge often appears as implicit commonsense
behind texts, designing probes for conceptual knowledge is hard. Inspired by
knowledge representation schemata, we comprehensively evaluate conceptual
knowledge of PLMs by designing three tasks to probe whether PLMs organize
entities by conceptual similarities, learn conceptual properties, and
conceptualize entities in contexts, respectively. For the tasks, we collect and
annotate 24k data instances covering 393 concepts, which is COPEN, a COnceptual
knowledge Probing bENchmark. Extensive experiments on different sizes and types
of PLMs show that existing PLMs systematically lack conceptual knowledge and
suffer from various spurious correlations. We believe this is a critical
bottleneck for realizing human-like cognition in PLMs. COPEN and our codes are
publicly released at https://github.com/THU-KEG/COPEN.Comment: Accepted by EMNLP 202
- ā¦