Busy toy designs reduce the specificity of mothers' references to toy parts during toy play with their toddlers

When a parent is playing with a toy with his or her child, might a toy's "busy" visual design negatively impact the specificity and quality of the parent's talk? In this study, 24 mother-toddler (M = 23.5 months) dyads played with both (a) unmodified visually busy commercial toys and (b) modified visually "simple" versions of these commercial toys. Our focus was on the specificity of mothers' 552 references to the main parts of the toys (i.e., the rings of a stacking ring toy and the blocks of a nesting block toy), which was found to be impacted by the toys' visual design. That is, with simple toys, mothers produced a significantly greater proportion of specific references (e.g., the blue ring) than non-specific references (e.g., this/that one). Indeed, the proportion of specific references was three times greater in play with the simple toys than with the busy toys. Busy toys also reduced the number of references to parts of the toy overall and children's exposure to vocabulary such as colour terms used within specific references. These results underscore that the visual design of toys is an important aspect to consider, particularly in contexts where the goal may be to foster adult-child language and a child's exposure to more information-rich vocabulary terms during toy play with an adult. © 2019, Canadian Association of Speech-Language Pathologists and Audiologists. All rights reserved

Time of arrival through interacting environments: Tunneling processes

We discuss the propagation of wave packets through interacting environments. Such environments generally modify the dispersion relation or shape of the wave function. To study such effects in detail, we define the distribution function P_{X}(T), which describes the arrival time T of a packet at a detector located at point X. We calculate P_{X}(T) for wave packets traveling through a tunneling barrier and find that our results actually explain recent experiments. We compare our results with Nelson's stochastic interpretation of quantum mechanics and resolve a paradox previously apparent in Nelson's viewpoint about the tunneling time.Comment: Latex 19 pages, 11 eps figures, title modified, comments and references added, final versio

Source and purity of dengue-viral preparations impact requirement for enhancing antibody to induce elevated IL-1β secretion: A primary human monocyte model

Dengue virus is a major global health threat and can lead to life-threatening hemorrhagic complications due to immune activation and cytokine production. Cross-reactive antibodies to an earlier dengue virus infection are a recognized risk factor for severe disease. These antibodies bind heterologous dengue serotypes and enhance infection into Fc-receptorbearing cells, a process known as antibody-dependent enhancement of infection. One crucial cytokine seen elevated in severe dengue patients is IL-1β, a potent inflammatory cytokine matured by the inflammasome. We used a highly-physiologic system by studying antibody-dependent enhancement of IL-1β in primary human monocytes with anti-dengue human monoclonal antibodies isolated from patients. Antibody-enhancement increased viral replication in primary human monocytes inoculated with supernatant harvested from Vero cells infected with dengue virus serotype 2 (DENV-2) 16681. Surprisingly, IL-1β secretion induced by infectious supernatant harvested from two independent Vero cell lines was not enhanced by antibody. Secretion of multiple other inflammatory cytokines was also independent of antibody signaling. However, IL-1β secretion did require NLRP3 and caspase- 1 activity. Immunodepletion of dengue virions from the infectious supernatant confirmed that virus was not the main IL-1β-inducing agent, suggesting that a supernatant component(s) not associated with the virion induced IL-1β production. We excluded RNA, DNA, contaminating LPS, viral NS1 protein, complement, and cytokines. In contrast, purified Vero-derived DENV-2 16681 exhibited antibody-enhancement of both infection and IL-1β induction. Furthermore, C6/36 mosquito cells did not produce such an inflammatory component, as crude supernatant harvested from insect cells infected with DENV-2 16681 induced antibody-dependent IL-1β secretion. This study indicates that Vero cells infected with DENV-2 16681 may produce inflammatory components during dengue virus propagation that mask the virus-specific immune response. Thus, the choice of host cell and viral purity should be carefully considered, while insect-derived virus represents a systemthat elicits antibody- dependent cytokine responses to dengue virus with fewer confounding issues

Restricted and Repetitive Behavior and Brain Functional Connectivity in Infants at Risk for Developing Autism Spectrum Disorder

Background: Restricted and repetitive behaviors (RRBs), detectable by 12 months in many infants in whom autism spectrum disorder (ASD) is later diagnosed, may represent some of the earliest behavioral markers of ASD. However, brain function underlying the emergence of these key behaviors remains unknown. Methods: Behavioral and resting-state functional connectivity (fc) magnetic resonance imaging data were collected from 167 children at high and low familial risk for ASD at 12 and 24 months (n = 38 at both time points). Twenty infants met criteria for ASD at 24 months. We divided RRBs into four subcategories (restricted, stereotyped, ritualistic/sameness, self-injurious) and used a data-driven approach to identify functional brain networks associated with the development of each RRB subcategory. Results: Higher scores for ritualistic/sameness behavior were associated with less positive fc between visual and control networks at 12 and 24 months. Ritualistic/sameness and stereotyped behaviors were associated with less positive fc between visual and default mode networks at 12 months. At 24 months, stereotyped and restricted behaviors were associated with more positive fc between default mode and control networks. Additionally, at 24 months, stereotyped behavior was associated with more positive fc between dorsal attention and subcortical networks, whereas restricted behavior was associated with more positive fc between default mode and dorsal attention networks. No significant network-level associations were observed for self-injurious behavior. Conclusions: These observations mark the earliest known description of functional brain systems underlying RRBs, reinforce the construct validity of RRB subcategories in infants, and implicate specific neural substrates for future interventions targeting RRBs

Discovery of potent and selective MRCK inhibitors with therapeutic effect on skin cancer

The myotonic dystrophy-related Cdc42-binding kinases MRCKα and MRCKβ contribute to the regulation of actin-myosin cytoskeleton organization and dynamics, acting in concert with the Rho-associated coiled-coil kinases ROCK1 and ROCK2. The absence of highly potent and selective MRCK inhibitors has resulted in relatively little knowledge of the potential roles of these kinases in cancer. Here we report the discovery of the azaindole compounds BDP8900 and BDP9066 as potent and selective MRCK inhibitors that reduce substrate phosphorylation, leading to morphological changes in cancer cells along with inhibition of their motility and invasive character. In over 750 human cancer cell lines tested, BDP8900 and BDP9066 displayed consistent anti-proliferative effects with greatest activity in hematological cancer cells. Mass spectrometry identified MRCKα S1003 as an autophosphorylation site, enabling development of a phosphorylation-sensitive antibody tool to report on MRCKα status in tumor specimens. In a two-stage chemical carcinogenesis model of murine squamous cell carcinoma, topical treatments reduced MRCKα S1003 autophosphorylation and skin papilloma outgrowth. In parallel work, we validated a phospho-selective antibody with the capability to monitor drug pharmacodynamics. Taken together, our findings establish an important oncogenic role for MRCK in cancer, and they offer an initial preclinical proof of concept for MRCK inhibition as a valid therapeutic strategy

Coherent Photoproduction of pi^+ from 3^He

We have measured the differential cross section for the $\gamma$$^3$He$\rightarrow \pi^+ t$ reaction. This reaction was studied using the CEBAF Large Acceptance Spectrometer (CLAS) at Jefferson Lab. Real photons produced with the Hall-B bremsstrahlung tagging system in the energy range from 0.50 to 1.55 GeV were incident on a cryogenic liquid $^3$He target. The differential cross sections for the $\gamma$$^3$He$\rightarrow \pi^+ t$ reaction were measured as a function of photon-beam energy and pion-scattering angle. Theoretical predictions to date cannot explain the large cross sections except at backward angles, showing that additional components must be added to the model.Comment: 11 pages, 16 figure

Precise Measurements of Beam Spin Asymmetries in Semi-Inclusive π0\pi^0 production

We present studies of single-spin asymmetries for neutral pion electroproduction in semi-inclusive deep-inelastic scattering of 5.776 GeV polarized electrons from an unpolarized hydrogen target, using the CEBAF Large Acceptance Spectrometer (CLAS) at the Thomas Jefferson National Accelerator Facility. A substantial $\sin \phi_h$ amplitude has been measured in the distribution of the cross section asymmetry as a function of the azimuthal angle $\phi_h$ of the produced neutral pion. The dependence of this amplitude on Bjorken $x$ and on the pion transverse momentum is extracted with significantly higher precision than previous data and is compared to model calculations.Comment: to be submitted PL

Plant extracts in cell-based anti-inflammatory assays—Pitfalls and considerations related to removal of activity masking bulk components

Plants used in traditional medicine represent an important source of new lead compounds. However, cell-based in vitro screening assays with plant material are hampered by the complex nature of plant extracts as mixtures of active and inactive components. Bulk constituents, such as chlorophyll and polyphenols were previously shown to interfere with several biological in vitro assays. Their influence on anti-inflammatory cell-based testing systems has not been thoroughly investigated. Hence, the present study was aimed at comparing different procedures for the removal of bulk constituents from plant extracts and examining the influence of their elimination on selected cell-based anti-inflammatory assays. Malva sp. and Glechoma hederacea L., two plants used in traditional European medicine for the treatment of inflammatory disorders, were subjected to three different methods for the removal of chlorophyll and polyphenols, respectively. Removal of bulk constituents was confirmed by HPLC and mass spectrometry. Extracts were tested before and after the purification procedure, to determine their potential to inhibit the activation of the transcription factor NF-κB in reporter gene assay and to interfere with the secretion of the chemokine IL-8 after stimulation of endothelial cells with tumor necrosis factor (TNF-α) or lipopolysaccharide (LPS). Removal of chlorophyll from tested extracts led to a strong decrease in the anti-inflammatory activities, due to loss of bioactive constituents. In contrast, the effect of the polyphenol-free extracts was either not changed or significantly increased, depending on the purification method used. The study concluded that clearance of bulk compounds represents a valuable strategy for cell-based in vitro anti-inflammatory evaluation of plant extracts. Liquid–liquid partitioning was identified as the optimal method for the elimination of both chlorophyll and polyphenols. It is recommended that removal of chlorophyll from extracts always be accompanied by HPLC profiling to detect a possible loss of active constituents

The geology and geophysics of Kuiper Belt object (486958) Arrokoth

The Cold Classical Kuiper Belt, a class of small bodies in undisturbed orbits beyond Neptune, are primitive objects preserving information about Solar System formation. The New Horizons spacecraft flew past one of these objects, the 36 km long contact binary (486958) Arrokoth (2014 MU69), in January 2019. Images from the flyby show that Arrokoth has no detectable rings, and no satellites (larger than 180 meters diameter) within a radius of 8000 km, and has a lightly-cratered smooth surface with complex geological features, unlike those on previously visited Solar System bodies. The density of impact craters indicates the surface dates from the formation of the Solar System. The two lobes of the contact binary have closely aligned poles and equators, constraining their accretion mechanism

7th Drug hypersensitivity meeting: part two

No abstract availabl