Study Of The Ability To Detect Humor In Visual Images By 2-5 Year Olds

Problem Understanding the impact that humor can have as a form of therapy has been studied mostly in relation to mental and spiritual healing. As a result, little focus has been given to understanding the types of humor and how one’s understanding of and appreciation for types of humor develop over time. Gaining an understanding of humor development is important due to discoveries that the use of humor is a great intervention tool when working with children. Nevertheless, the use of pictures (with humor) is often used within speech therapy sessions, but seldom used correctly due to the lack of understanding of humor development in children. Method This study was carried out by individually removing each participant from the classroom A total of 12 pictures were presented to each child (i.e. three groups of four pictures) via the iPad. When the first photo grid was presented, the experimenter directed the participant’s attention to the reference picture, and created a story line to explain the reference picture. Then the experimenter directed the participant’s attention to the other three pictures by saying, “…Point to the picture that makes you laugh the most.” The participant then selected from the three alternatives, with the expected selection to be the one of incongruency. Each participant was given a range of 0 to 90 seconds to observe each photo grid and select a response. Results A Pearson product-moment correlation coefficient showed that there was a positive correlation on all of the dependent variables (types of humor) and some independent variables (i.e. language and gender), as well as between gender and hyperbolic humor type. Repeated measures ANOVA resulted in significant difference in participants’ ability to correctly identify incongruent elements in types of humor based on gender, language and age. A multiple regression analysis was done and resulted in there being a high level of significance for the independent variables age grouping, gender and language skills to operate as successful predictors of overall correct identification of incongruence in the dependent variables. Conclusion It is important to take into consideration the age, gender and type of humor as well as the language skill level of each client, because these aspects could have a major impact on the success or failure of a session and overall work with a client

Application of a mixed variational higher order plate theory towards understanding the deformation behavior of hybrid laminates

Hybrid laminates containing an elastomer layer in addition to fiber reinforced polymer as well as metal layers have been found beneficial in compensating issues frequently found with traditional fiber metal laminates. Commonly used equivalent single-layer shell and plate theories, however, are unable to account for the strong heterogeneous stiffness distribution of the constituents within the laminate. Furthermore, the transverse shear and normal deformations in the elastomer layer are expected to significantly influence the deformation of the neighboring laminae. An accurate depiction of these transverse stresses requires a multi-layer shell theory as opposed to commonly used single-layer formulations. Hence, a higher order mixed variational plate theory is applied in order to study and predict the mechanical behavior of such laminates, especially on a structural level where the computational effort forbids the use of a three dimensional continuum formulation

A multidimensional metabolomics workflow to image biodistribution and evaluate pharmacodynamics in adult zebrafish

An integrated evaluation of the tissue distribution and pharmacodynamic properties of a therapeutic is essential for successful translation to the clinic. To date, however, cost-effective methods to measure these parameters at the systems level in model organisms are lacking. Here, we introduce a multidimensional workflow to evaluate drug activity that combines mass spectrometry-based imaging, absolute drug quantitation across different biological matrices, in vivo isotope tracing and global metabolome analysis in the adult zebrafish. As a proof of concept, we quantitatively determined the whole-body distribution of the anti-rheumatic agent hydroxychloroquine sulfate (HCQ) and measured the systemic metabolic impacts of drug treatment. We found that HCQ distributed to most organs in the adult zebrafish 24 h after addition of the drug to water, with the highest accumulation of both the drug and its metabolites being in the liver, intestine and kidney. Interestingly, HCQ treatment induced organ-specific alterations in metabolism. In the brain, for example, HCQ uniquely elevated pyruvate carboxylase activity to support increased synthesis of the neuronal metabolite, N-acetylaspartate. Taken together, this work validates a multidimensional metabolomics platform for evaluating the mode of action of a drug and its potential off-target effects in the adult zebrafish. This article has an associated First Person interview with the first author of the paper

Wide Scale Characterization and Modeling of the Vibration and Damping Behavior of CFRP-Elastomer-Metal Laminates—Comparison and Discussion of Different Test Setups

The investigated hybrid carbon fiber reinforced plastics-elastomer-metal laminates (HyCEML) offer the potential of tailored structural materials with adaptable damping properties. Conventional fiber metal laminates, like glass laminate aluminum reinforced epoxy are already widely spread in the aviation industry owing to their outstanding fatigue behavior. By integrating an elastomeric interlayer, the glass fibers can be substituted by carbon fibers and damping properties of these laminates can be adjusted. The viscoelastic interlayer dissipates energy within the laminate by inducing shear strain during bending, which is commonly known as constrained layer damping. The aim of this paper is the description of the vibration and damping behavior of HyCEML over a wide temperature and frequency range by using different test methods. Dynamic mechanical analysis is used for the individual polymeric constituents and coupon specimens and modal analysis is used with different specimen geometries up to a component sized panel. In addition, analytical and numerical approaches complement the experiments and lead to a deeper understanding of the vibration and damping behavior. Owing to the high damping, already at frequencies of 5 kHz only running waves can be detected for the investigated panel size. The discussion of different test methods helps to identify material and wavelength dependent effects, but also possible adverse effects of certain methods

LRG1 destabilizes tumor vessels and restricts immunotherapeutic potency

BACKGROUND: A poorly functioning tumor vasculature is pro-oncogenic and may impede the delivery of therapeutics. Normalizing the vasculature, therefore, may be beneficial. We previously reported that the secreted glycoprotein leucine-rich α-2-glycoprotein 1 (LRG1) contributes to pathogenic neovascularization. Here, we investigate whether LRG1 in tumors is vasculopathic and whether its inhibition has therapeutic utility. METHODS: Tumor growth and vascular structure were analyzed in subcutaneous and genetically engineered mouse models in wild-type and Lrg1 knockout mice. The effects of LRG1 antibody blockade as monotherapy, or in combination with co-therapies, on vascular function, tumor growth, and infiltrated lymphocytes were investigated. FINDINGS: In mouse models of cancer, Lrg1 expression was induced in tumor endothelial cells, consistent with an increase in protein expression in human cancers. The expression of LRG1 affected tumor progression as Lrg1 gene deletion, or treatment with a LRG1 function-blocking antibody, inhibited tumor growth and improved survival. Inhibition of LRG1 increased endothelial cell pericyte coverage and improved vascular function, resulting in enhanced efficacy of cisplatin chemotherapy, adoptive T cell therapy, and immune checkpoint inhibition (anti-PD1) therapy. With immunotherapy, LRG1 inhibition led to a significant shift in the tumor microenvironment from being predominantly immune silent to immune active. CONCLUSIONS: LRG1 drives vascular abnormalization, and its inhibition represents a novel and effective means of improving the efficacy of cancer therapeutics

Loss of BCL9/9l suppresses Wnt driven tumourigenesis in models that recapitulate human cancer.

Different thresholds of Wnt signalling are thought to drive stem cell maintenance, regeneration, differentiation and cancer. However, the principle that oncogenic Wnt signalling could be specifically targeted remains controversial. Here we examine the requirement of BCL9/9l, constituents of the Wnt-enhanceosome, for intestinal transformation following loss of the tumour suppressor APC. Although required for Lgr5+ intestinal stem cells and regeneration, Bcl9/9l deletion has no impact upon normal intestinal homeostasis. Loss of BCL9/9l suppressed many features of acute APC loss and subsequent Wnt pathway deregulation in vivo. This resulted in a level of Wnt pathway activation that favoured tumour initiation in the proximal small intestine (SI) and blocked tumour growth in the colon. Furthermore, Bcl9/9l deletion completely abrogated β-catenin driven intestinal and hepatocellular transformation. We speculate these results support the just-right hypothesis of Wnt-driven tumour formation. Importantly, loss of BCL9/9l is particularly effective at blocking colonic tumourigenesis and mutations that most resemble those that occur in human cancer

Oncogenic BRAF, unrestrained by TGFβ-receptor signalling, drives right-sided colonic tumorigenesis.

Right-sided (proximal) colorectal cancer (CRC) has a poor prognosis and a distinct mutational profile, characterized by oncogenic BRAF mutations and aberrations in mismatch repair and TGFβ signalling. Here, we describe a mouse model of right-sided colon cancer driven by oncogenic BRAF and loss of epithelial TGFβ-receptor signalling. The proximal colonic tumours that develop in this model exhibit a foetal-like progenitor phenotype (Ly6a/Sca1+) and, importantly, lack expression of Lgr5 and its associated intestinal stem cell signature. These features are recapitulated in human BRAF-mutant, right-sided CRCs and represent fundamental differences between left- and right-sided disease. Microbial-driven inflammation supports the initiation and progression of these tumours with foetal-like characteristics, consistent with their predilection for the microbe-rich right colon and their antibiotic sensitivity. While MAPK-pathway activating mutations drive this foetal-like signature via ERK-dependent activation of the transcriptional coactivator YAP, the same foetal-like transcriptional programs are also initiated by inflammation in a MAPK-independent manner. Importantly, in both contexts, epithelial TGFβ-receptor signalling is instrumental in suppressing the tumorigenic potential of these foetal-like progenitor cells