Semantic Processing Disturbance in Patients with Schizophrenia: A Meta-Analysis of the N400 Component

Background: Theoretically semantic processing can be separated into early automatic semantic activation and late contextualization. Semantic processing deficits have been suggested in patients with schizophrenia, however it is not clear which stage of semantic processing is impaired. We attempted to clarify this issue by conducting a meta-analysis of the N400 component.</p

Differential Protein Expression in Small Intestinal Neuroendocrine Tumors and Liver Metastases

OBJECTIVE: Small intestinal neuroendocrine tumors (SI-NETs) are often detected after they have become metastatic. Using a novel protein array, we identified pathways important in SI-NET metastasis development in surgically resected patients. METHODS: Paired primary tumors and liver metastases from 25 patients undergoing surgical resection for metastatic SI-NETs were harvested. Extracted proteins were separated by sodium dodecyl sulfate gel and multiplex immunoblots were performed with 136 antibodies. Significant Analysis of Microarray was used to select for differentially expressed proteins. A tissue microarray was constructed from 27 archived specimens and stained by immunohistochemistry. RESULTS: Comparing primary SI-NETs with matched normal small-bowel mucosa, 9 proteins were upregulated and cyclin E was downregulated. The SI-NET liver metastases demonstrated upregulation of P-ERK and p27 but downregulation of CDK2 and CDC25B. When comparing primary SI-NET with their paired liver metastases, cyclin E demonstrated a significant upregulation in the liver metastasis. Tissue microarray demonstrated higher p38 expression and lower Cdc 25b expression in SI-NETs versus liver metastases and confirmed higher expression of p27 in liver metastases versus normal liver. CONCLUSIONS: Few studies have compared protein expression in paired primary and metastatic SI-NETs. Our findings reveal changes in a limited number of proteins, suggesting that these may be targets for therapy

Mus musculus deficient for secretory antibodies show delayed growth with an altered urinary metabolome

© 2019 The Author(s). Background: The polymeric immunoglobulin receptor (pIgR) maintains the integrity of epithelial barriers by transporting polymeric antibodies and antigens through the epithelial mucosa into the lumen. In this study, we examined the role of pIgR in maintaining gut barrier integrity, which is important for the normal development in mice. Methods: Cohorts of pIgR -/- mice and their wildtype controls were housed under Specific Pathogen Free (SPF) conditions and monitored for weight gain as an indicator of development over time. The general physiology of the gastrointestinal tract was analysed using immunohistochemistry in young (8-12 weeks of age) and aged mice (up to 18 months of age), and the observed immunopathology in pIgR -/- mice was further characterised using flow cytometry. Urinary metabolites were analysed using gas chromatography-mass spectrometry (GC-MS), which revealed changes in metabolites that correlated with age-related increase in gut permeability in pIgR -/- mice. Results: We observed that pIgR -/- mice exhibited delayed growth, and this phenomenon is associated with low-grade gut inflammation that increased with ageing. The gross intraepithelial lymphocytic (IEL) infiltration characteristic of pIgR -/- mice was redefined as CD8α+αβ+ T cells, the majority of which expressed high levels of CD103 and CD69 consistent with tissue resident memory T cells (TRM). Comparison of the urinary metabolome between pIgR -/- and wild-type mice revealed key changes in urinary biomarkers fucose, glycine and Vitamin B5, suggestive of altered mucosal permeability. A significant increase in gut permeability was confirmed by analysing the site-specific uptake of sugar probes in different parts of the intestine. Conclusion: Our data show that loss of the secretory antibody system in mice results in enhanced accumulation of inflammatory IELs in the gut, which likely reflects ongoing inflammation in reaction to gut microbiota or food antigens, leading to delayed growth in pIgR -/- mice. We demonstrate that this leads to the presence of a unique urinary metabolome profile, which may provide a biomarker for altered gut permeability

Competitive Benchmarking: An IS Research Approach to Address Wicked Problems with Big Data and Analytics

Wicked problems like sustainable energy and financial market stability are societal challenges that arise from complex socio-technical systems in which numerous social, economic, political, and technical factors interact. Understanding and mitigating them requires research methods that scale beyond the traditional areas of inquiry of Information Systems (IS) “individuals, organizations, and markets” and that deliver solutions in addition to insights. We describe an approach to address these challenges through Competitive Benchmarking (CB), a novel research method that helps interdisciplinary research communities to tackle complex challenges of societal scale by using different types of data from a variety of sources such as usage data from customers, production patterns from producers, public policy and regulatory constraints, etc. for a given instantiation. Further, the CB platform generates data that can be used to improve operational strategies and judge the effectiveness of regulatory regimes and policies. We describe our experience applying CB to the sustainable energy challenge in the Power Trading Agent Competition (Power TAC) in which more than a dozen research groups from around the world jointly devise, benchmark, and improve IS-based solutions

Optimization of the upper surface of hypersonic vehicle based on CFD analysis

For the hypersonic vehicle, the aerodynamic performance becomes more intensive. Therefore, it is a significant event to optimize the shape of the hypersonic vehicle to achieve the project demands. It is a key technology to promote the performance of the hypersonic vehicle with the method of shape optimization. Based on the existing vehicle, the optimization to the upper surface of the Simplified hypersonic vehicle was done to obtain a shape which suits the project demand. At the cruising condition, the upper surface was parameterized with the B-Spline curve method. The incremental parametric method and the reconstruction technology of the local mesh were applied here. The whole flow field was been calculated and the aerodynamic performance of the craft were obtained by the computational fluid dynamic (CFD) technology. Then the vehicle shape was optimized to achieve the maximum lift-drag ratio at attack angle 3 degrees, 4 degrees and 5 degrees. The results will provide the reference for the practical design

Pan-cancer analysis of whole genomes

Cancer is driven by genetic change, and the advent of massively parallel sequencing has enabled systematic documentation of this variation at the whole-genome scale(1-3). Here we report the integrative analysis of 2,658 whole-cancer genomes and their matching normal tissues across 38 tumour types from the Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium of the International Cancer Genome Consortium (ICGC) and The Cancer Genome Atlas (TCGA). We describe the generation of the PCAWG resource, facilitated by international data sharing using compute clouds. On average, cancer genomes contained 4-5 driver mutations when combining coding and non-coding genomic elements; however, in around 5% of cases no drivers were identified, suggesting that cancer driver discovery is not yet complete. Chromothripsis, in which many clustered structural variants arise in a single catastrophic event, is frequently an early event in tumour evolution; in acral melanoma, for example, these events precede most somatic point mutations and affect several cancer-associated genes simultaneously. Cancers with abnormal telomere maintenance often originate from tissues with low replicative activity and show several mechanisms of preventing telomere attrition to critical levels. Common and rare germline variants affect patterns of somatic mutation, including point mutations, structural variants and somatic retrotransposition. A collection of papers from the PCAWG Consortium describes non-coding mutations that drive cancer beyond those in the TERT promoter(4); identifies new signatures of mutational processes that cause base substitutions, small insertions and deletions and structural variation(5,6); analyses timings and patterns of tumour evolution(7); describes the diverse transcriptional consequences of somatic mutation on splicing, expression levels, fusion genes and promoter activity(8,9); and evaluates a range of more-specialized features of cancer genomes(8,10-18).Peer reviewe

More than smell - COVID-19 is associated with severe impairment of smell, taste, and chemesthesis

Recent anecdotal and scientific reports have provided evidence of a link between COVID-19 and chemosensory impairments, such as anosmia. However, these reports have downplayed or failed to distinguish potential effects on taste, ignored chemesthesis, and generally lacked quantitative measurements. Here, we report the development, implementation, and initial results of a multilingual, international questionnaire to assess self-reported quantity and quality of perception in 3 distinct chemosensory modalities (smell, taste, and chemesthesis) before and during COVID-19. In the first 11 days after questionnaire launch, 4039 participants (2913 women, 1118 men, and 8 others, aged 19-79) reported a COVID-19 diagnosis either via laboratory tests or clinical assessment. Importantly, smell, taste, and chemesthetic function were each significantly reduced compared to their status before the disease. Difference scores (maximum possible change ±100) revealed a mean reduction of smell (-79.7 ± 28.7, mean ± standard deviation), taste (-69.0 ± 32.6), and chemesthetic (-37.3 ± 36.2) function during COVID-19. Qualitative changes in olfactory ability (parosmia and phantosmia) were relatively rare and correlated with smell loss. Importantly, perceived nasal obstruction did not account for smell loss. Furthermore, chemosensory impairments were similar between participants in the laboratory test and clinical assessment groups. These results show that COVID-19-associated chemosensory impairment is not limited to smell but also affects taste and chemesthesis. The multimodal impact of COVID-19 and the lack of perceived nasal obstruction suggest that severe acute respiratory syndrome coronavirus strain 2 (SARS-CoV-2) infection may disrupt sensory-neural mechanisms. © 2020 The Author(s) 2020. Published by Oxford University Press. All rights reserved

Haptic Shared Control in Deep Sea Mining: Enhancing Teleoperation of a Subsea Crawler

Deep sea mining is currently being investigated as a possibility to harvest valuable materials from mineral-rich areas located in water depths up to 2000 meters. One promising mining method is to employ a large crawler on the seabed, remotely controlled by an operator on the supporting vessel. Controlling such a vehicle is expected to be difficult due to unpredictable seabed conditions and limited situation awareness of the operator. In addition, the optimal human-machine interface for controlling the crawler is yet to be determined. A common approach in marine operation is to automate the task as much as possible, leaving the operator in a supervisory role. An alternative approach is haptic shared control, which has shown to be beneficial in vehicle control tasks (automotive, UAVs), yielding improved performance but mitigating traditional human-automation interaction issues such as skill degradation, reduced situation awareness and overreliance. This study aims to compare supervisory control and haptic shared control to manual control of a teleoperated subsea crawler. A simulator was constructed, including a bi-manual control interface capable of rendering haptic feedback, two virtual displays showing primary and secondary task-related information, a mathematical model simulating the dynamics of the slow vehicle, and unpredictable soil properties of the seabed. In a human factor experiment, subjects (n=12) controlled the simulated crawler to complete normal steering, repeated obstacle avoidance, and an unexpected slip event at the end; all with manual control, haptic shared control and supervisory control. During normal steering between obstacles, both haptic shared control and supervisory control improved subjects’ performance and supervisory control allowed a significant decrease in control effort. However, during slip recovery and obstacle avoidance, supervisory control appreciably reduced subjects’ situation awareness. Therefore haptic shared control is a promising approach to assist the operator in underwater teleoperation with improved task performance but not the side-effects from the automationBMDBioMechanical EngineeringMechanical, Maritime and Materials Engineerin

An Investigation of 800kHz Flyback

A 800kHz flyback with input voltage 350V and output 20V, 150W is designed in this thesis. The goal of the investigation is to reveal the problems during the designing process when flyback converter goes to high frequency. Because of the fact that boundary conduction mode (BCM) operation exhibits the lowest possible switching losses, the investigation is to reduce those losses as low as possible and is done on BCM, as that way of operation looks most suitable. The outcome shows the feasibility of the high frequency flyback converter and some precautious for future design. A simulation model is made that well matches the real circuit waveforms.Power electronicsElectrical Power EngineeringElectrical Engineering, Mathematics and Computer Scienc

Fabrication of Living Entangled Network Composites Enabled by Mycelium

Organic polymer-based composite materials with favorable mechanical performance and functionalities are keystones to various modern industries; however, the environmental pollution stemming from their processing poses a great challenge. In this study, by finding an autonomous phase separating ability of fungal mycelium, a new material fabrication approach is introduced that leverages such biological metabolism-driven, mycelial growth-induced phase separation to bypass high-energy cost and labor-intensive synthetic methods. The resulting self-regenerative composites, featuring an entangled network structure of mycelium and assembled organic polymers, exhibit remarkable self-healing properties, being capable of reversing complete separation and restoring ≈90% of the original strength. These composites further show exceptional mechanical strength, with a high specific strength of 8.15 MPa g.cm−3, and low water absorption properties (≈33% after 15 days of immersion). This approach spearheads the development of state-of-the-art living composites, which directly utilize bioactive materials to “self-grow” into materials endowed with exceptional mechanical and functional properties.Aerospace Manufacturing TechnologiesGroup MasaniaGeo-engineerin