Publications by authors named "SHAW A"

Akt is a master regulator of pro-growth signaling in the cell. Akt is activated by phosphoinositides that disrupt the autoinhibitory interface between the kinase and pleckstrin homology (PH) domains and then is phosphorylated at T308 and S473. Akt hyperactivation is oncogenic, which has spurred development of potent and selective inhibitors as therapeutics.

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Peatlands are crucial sinks for atmospheric carbon but are critically threatened due to warming climates. Sphagnum (peat moss) species are keystone members of peatland communities where they actively engineer hyperacidic conditions, which improves their competitive advantage and accelerates ecosystem-level carbon sequestration. To dissect the molecular and physiological sources of this unique biology, we generated chromosome-scale genomes of two Sphagnum species: S.

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Cyclic GMP-AMP synthase (cGAS) plays a key role in the innate immune responses to both DNA and RNA virus infection. Here, we found that enterovirus 71 (EV-A71), Seneca Valley virus (SVV), and foot-and-mouth disease virus (FMDV) infection triggered mitochondria damage and mitochondrial DNA (mtDNA) release in vitro and vivo. These responses were mediated by picornavirus 2B proteins which induced mtDNA release during viral replication.

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Introduction: There is a gap between aspiring to co-produce and co-create value in integrated healthcare and realising that in practice, particularly with complex needs and multiple stakeholders. Key principles from literature on value-based healthcare offer a conceptual framework for building suitable care platforms to support practice. This paper outlines the Complex Care and Recovery Management Framework (CCaRM) as an example of co-platforming value-based healthcare within case level practice.

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Background: There are limited randomized controlled trials with long-term outcomes comparing autologous chondrocyte implantation (ACI) versus alternative forms of surgical cartilage management within the knee.

Purpose: To determine at 5 years after surgery whether ACI was superior to alternative forms of cartilage management in patients after a failed previous treatment for chondral or osteochondral defects in the knee.

Study Design: Randomized controlled trial; Level of evidence, 1.

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Platelets are uniquely positioned as mediators of not only hemostasis but also innate immunity. However, how age and geriatric conditions such as frailty influence platelet function during an immune response remains unclear. We assessed the platelet transcriptome at baseline and following influenza vaccination in Younger (age 21-35) and Older (age ≥65) adults (including community-dwelling individuals who were largely non-frail and skilled nursing facility (SNF)-resident adults who nearly all met criteria for frailty).

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Producing quantum states at random has become increasingly important in modern quantum science, with applications being both theoretical and practical. In particular, ensembles of such randomly distributed, but pure, quantum states underlie our understanding of complexity in quantum circuits and black holes, and have been used for benchmarking quantum devices in tests of quantum advantage. However, creating random ensembles has necessitated a high degree of spatio-temporal control placing such studies out of reach for a wide class of quantum systems.

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Background: The gastrointestinal (GI) microbiota has been linked to health consequences throughout life, from early life illnesses (e.g. sepsis and necrotising enterocolitis) to lifelong chronic conditions such as obesity and inflammatory bowel disease.

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What are creative employees like, aside from being high on Openness to Experience? Based on a sample of 170 full-time working professionals in the consulting industry, the present study investigated the Big Five personality predictors of both supervisory perceptions and performance ratings of creative individuals at work. Results suggested that those with higher Openness and Extraversion but lower Agreeableness, were more likely to be perceived as creative people by their supervisors. In terms of their actual creative performance on the job, employees with higher Openness, Extraversion, and Conscientiousness, received better supervisory ratings.

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The first Cardiovascular Outcomes Research in Perioperative Medicine (COR-PM) conference took place on May 13, 2022, in Palm Springs, CA, and online. Here, we: (1) summarize the background, objective, and aims of the COR-PM meeting; (2) describe the conduct of the meeting; and (3) outline future directions for scientific meetings aimed at fostering high-quality clinical research in the broader perioperative medicine community.

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The algorithmic error of digital quantum simulations is usually explored in terms of the spectral norm distance between the actual and ideal evolution operators. In practice, this worst-case error analysis may be unnecessarily pessimistic. To address this, we develop a theory of average-case performance of Hamiltonian simulation with random initial states.

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Chatbots, web-based artificial intelligence tools that simulate human conversation, are increasingly in use to support many areas of genomic medicine. However, patient preferences towards using chatbots across the range of clinical settings are unknown. We conducted a qualitative study with individuals who underwent genetic testing for themselves or their child.

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Disruption to protein homeostasis caused by lysosomal dysfunction and associated impairment of autophagy is a prominent pathology in amyotrophic lateral sclerosis and frontotemporal dementia (ALS/FTD). The most common genetic cause of ALS/FTD is a G4C2 hexanucleotide repeat expansion in (C9ALS/FTD). Repeat-associated non-AUG (RAN) translation of G4C2 repeat transcripts gives rise to dipeptide repeat (DPR) proteins that have been shown to be toxic and may contribute to disease etiology.

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T cell-B cell interaction is the key immune response to protect the host from severe viral infection. However, how T cells support B cells to exert protective humoral immunity in humans is not well understood. Here, we use COVID-19 as a model of acute viral infections and analyze CD4 T cell subsets associated with plasmablast expansion and clinical outcome.

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Background: After a median follow-up of 18·3 months, the third-generation anaplastic lymphoma kinase (ALK) tyrosine-kinase inhibitor, lorlatinib, improved progression-free survival in patients with treatment-naive, ALK-positive non-small-cell lung cancer in the phase 3 CROWN study. Here we report updated efficacy data, including intracranial activity, from an unplanned analysis after 3 years of follow-up.

Methods: CROWN is an ongoing, international, randomised, open-label phase 3 trial done in 104 centres in 23 countries worldwide.

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Synaptic loss occurs early in many neurodegenerative diseases and contributes to cognitive impairment even in the absence of gross atrophy. Currently, for human disease there are few formal models to explain how cortical networks underlying cognition are affected by synaptic loss. We advocate that biophysical models of neurophysiology offer both a bridge from preclinical to clinical models of pathology and quantitative assays for experimental medicine.

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Antibodies are essential biological research tools and important therapeutic agents, but some exhibit non-specific binding to off-target proteins and other biomolecules. Such polyreactive antibodies compromise screening pipelines, lead to incorrect and irreproducible experimental results, and are generally intractable for clinical development. Here, we design a set of experiments using a diverse naïve synthetic camelid antibody fragment (nanobody) library to enable machine learning models to accurately assess polyreactivity from protein sequence (AUC > 0.

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The formation of complexes between Rab11 and its effectors regulates multiple aspects of membrane trafficking, including recycling and ciliogenesis. WD repeat-containing protein 44 (WDR44) is a structurally uncharacterized Rab11 effector that regulates ciliogenesis by competing with prociliogenesis factors for Rab11 binding. Here, we present a detailed biochemical and biophysical characterization of the WDR44-Rab11 complex and define specific residues mediating binding.

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The aim of the study was to determine the impact of internal and external (proximal and distal) attentional focus on table tennis backhand stroke accuracy in low-skilled players. Fifty-one undergraduate physical education (PE) students were randomly assigned to 3 groups: Group G1 (IF) was instructed to focus on the hand holding the paddle, Group G2 (EFP) was instructed to focus on the ball, while Group G3 (EFD) was instructed to focus on targets marked on the tennis table. The experimental groups followed identical instructions except for the instruction about the focus of attention.

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Introduction of the solid phase method to synthesize biopolymers has revolutionized the field of biological research by enabling efficient production of peptides and oligonucleotides. One of the advantages of this method is the ease of removal of excess production materials from the desired product, as it is immobilized on solid substrate. The DNA origami method utilizes the nature of nucleotide base-pairing to construct well-defined objects at the nanoscale, and has become a potent tool for manipulating matter in the fields of chemistry, physics, and biology.

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Objectives: Quality of life (QoL) for patients with non-small cell lung cancer (NSCLC) is negatively impacted by their disease and treatment side effects. We present detailed patient-reported outcome (PRO) data from the phase 3 CROWN study, which compared lorlatinib with crizotinib in patients with previously untreated ALK-positive advanced NSCLC.

Materials And Methods: PROs were assessed using the European Organisation for Research and Treatment of Cancer QoL Questionnaire with Lung Cancer module.

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Population size changes and gene flow are processes that can have significant impacts on evolution. The aim of this study was to investigate the relationship of geography to patterns of gene flow and population size changes in a pair of closely related (peatmoss) species: and . Both species occur in eastern North America, and also occurs in Europe.

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