Prometheus Research (United States)

Existential rules, a.k.a. tuple-generating dependencies (TGDs), form a well-established formalism for specifying ontologies. In particular, the warded language is a well-behaved fragment of TGD-based ontologies, striking a good balance between expressive power and computational complexity of answering Ontology-Mediated Queries (OMQs). The theoretical foundations of answering OMQs over warded ontologies are by now well-understood, but to the best of our knowledge, very few efforts exist that exploit such a rich theory for building practical query answering algorithms. Our goal is to fill the above gap by designing a novel Datalog rewriting algorithm for OMQs over warded ontologies which is amenable to practical implementations, as well as providing an implementation and an experimental evaluation, with the aim of understanding how key input parameters affect the performance of this approach, and what are its limits when combined with off-the-shelf Datalog-based engines.

Skeletal development depends on coordinated angiogenesis and osteogenesis. Bone morphogenetic proteins direct bone formation in part by activating SMAD1/5 signaling in osteoblasts. However, the role of SMAD1/5 in skeletal endothelium is unknown. Here, we found that endothelial cell-conditional SMAD1/5 depletion in juvenile mice caused metaphyseal and diaphyseal hypervascularity, resulting in altered trabecular and cortical bone formation. SMAD1/5 depletion induced excessive sprouting and disrupting the morphology of the metaphyseal vessels, with impaired anastomotic loop formation at the chondro-osseous junction. Endothelial SMAD1/5 depletion impaired growth plate resorption and, upon long-term depletion, abrogated osteoprogenitor recruitment to the primary spongiosa. Finally, in the diaphysis, endothelial SMAD1/5 activity was necessary to maintain the sinusoidal phenotype, with SMAD1/5 depletion inducing formation of large vascular loops and elevated vascular permeability. Together, endothelial SMAD1/5 activity sustains skeletal vascular morphogenesis and function and coordinates growth plate remodeling and osteoprogenitor recruitment dynamics in juvenile mouse bone.

Using elementary properties of primitive multiplicative characters we derive the autocorrelation of a unimodular <inline-formula xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink"> <tex-math notation="LaTeX">$M$ </tex-math></inline-formula> -ary character-based sequence of length <inline-formula xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink"> <tex-math notation="LaTeX">$pq$ </tex-math></inline-formula> , where <inline-formula xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink"> <tex-math notation="LaTeX">$p$ </tex-math></inline-formula> and <inline-formula xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink"> <tex-math notation="LaTeX">$q$ </tex-math></inline-formula> are distinct odd primes. Subsequently: (1) we identify three new sets of twin-prime quadriphase sequences with the largest autocorrelation sidelobe magnitude equal to <inline-formula xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink"> <tex-math notation="LaTeX">$\sqrt {5}$ </tex-math></inline-formula> or 3, (2) we show that the smallest maximum autocorrelation sidelobe magnitude of an <inline-formula xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink"> <tex-math notation="LaTeX">$M$ </tex-math></inline-formula> -ary character-based sequence, when <inline-formula xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink"> <tex-math notation="LaTeX">$4|M$ </tex-math></inline-formula> , either decreases with <inline-formula xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink"> <tex-math notation="LaTeX">$M$ </tex-math></inline-formula> and tends to 2, when <inline-formula xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink"> <tex-math notation="LaTeX">$6\nmid M$ </tex-math></inline-formula> , or is equal to 2, when <inline-formula xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink"> <tex-math notation="LaTeX">$6|M$ </tex-math></inline-formula> , and (3), we show that the smallest maximum autocorrelation sidelobe magnitude of a full-alphabet <inline-formula xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink"> <tex-math notation="LaTeX">$M$ </tex-math></inline-formula> -ary character-based sequence, where <inline-formula xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink"> <tex-math notation="LaTeX">$M&gt;2$ </tex-math></inline-formula> , is greater or equal to <inline-formula xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink"> <tex-math notation="LaTeX">$\sqrt {3}$ </tex-math></inline-formula> , and, in particular, is equal to <inline-formula xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink"> <tex-math notation="LaTeX">$\sqrt {3}$ </tex-math></inline-formula> for the sextic phase sequence.

Articular cartilage defects have limited healing potential and, when left untreated, can lead to osteoarthritis. Tissue engineering focuses on regenerating the damaged joint surface, preferably in an early stage. Here, we investigate the regenerative potential of three-dimensional (3D) constructs consisting of human induced pluripotent stem cell (iPSC)-derived chondrocytes in gelatin methacryloyl (GelMA) hydrogel for stable hyaline cartilage production. iPSC-derived chondrocytes are encapsulated in GelMA hydrogel at low (1 × 107 ml-1 ) and high (2 × 107 ml-1 ) density. In a conventional medium, GelMA hydrogel supports the chondrocyte phenotype, as opposed to cells cultured in 3D in absence of hydrogel. Moreover, encapsulated iPSC-derived chondrocytes preserve their in vivo matrix formation capacity after 21 days in vitro. In differentiation medium, hyaline cartilage-like tissue forms after 21 days, demonstrated by highly sulfated glycosaminoglycans and collagen type II. Matrix deposition is delayed at low encapsulation density, corroborating with lower transcript levels of COL2A1. An ectopic assay in nude mice demonstrates further maturation of the matrix deposited in vitro. Direct ectopic implantation of iPSC-derived chondrocyte-laden GelMA, without in vitro priming, also generates hyaline cartilage-like tissue, albeit less mature. Since it is unclear what maturity upon implantation is desired for joint surface regeneration, this is an attractive technology to generate immature and more mature hyaline cartilage-like tissue.

This report summarizes progress by an external entity (Prometheus Innovations LLC) that collaborated with PNNL on furthering the commercialization of materials science technologies to improve visibility of underwater netting for fish protection at hydropower dams.

Abstract Clinical research in neurodevelopmental disorders remains reliant upon clinician and caregiver measures. Limitations of these approaches indicate a need for objective, quantitative, and reliable biomarkers to advance clinical research. Extant research suggests the potential utility of multiple candidate biomarkers; however, effective application of these markers in trials requires additional understanding of replicability, individual differences, and intra-individual stability over time. The Autism Biomarkers Consortium for Clinical Trials (ABC-CT) is a multi-site study designed to investigate a battery of electrophysiological (EEG) and eye-tracking (ET) indices as candidate biomarkers for autism spectrum disorder (ASD). The study complements published biomarker research through: inclusion of large, deeply phenotyped cohorts of children with autism spectrum disorder (ASD) and typical development; a longitudinal design; a focus on well-evidenced candidate biomarkers harmonized with an independent sample; high levels of clinical, regulatory, technical, and statistical rigor; adoption of a governance structure incorporating diverse expertise in the ASD biomarker discovery and qualification process; prioritization of open science, including creation of a repository containing biomarker, clinical, and genetic data; and use of economical and scalable technologies that are applicable in developmental populations and those with special needs. The ABC-CT approach has yielded encouraging results, with one measure accepted into the FDA’s Biomarker Qualification Program to date. Through these advances, the ABC-CT and other biomarker studies in progress hold promise to deliver novel tools to improve clinical trials research in ASD.

This paper discusses the relevance in Ethics of the notion of human being. It distinguishes between the sphere of real moral moral practices and the philosophical foundation of such practices. It discusses also the difference between the modern concept of person and that of human being and establishes their role in moral thought. Finally, it focuses on the classical concept of person.

<h3>Introduction</h3> Overexpression and activation of the components of the EGFR/ErbB pathway has a prognostic significance in CRLM. HER2 (ErbB2) and HER3 (ErbB3) have previously been found to be overexpressed in CRLM with ErbB3 overexpression being associated with good prognosis. The ErbB signalling pathway consists of multiple molecular components. These components interact in a complex non-linear manner which makes it challenging to understand how the system functions. For example, the dimerization between ErbB receptors plays a crucial role in downstream signalling activation. Mathematical modelling can help to quantify network properties and understand its behaviour under various conditions. Birtwistle (2007) developed a mathematical model of the EGFR signalling pathway which focused on early pathway response to stimulation of the ErbB receptors. Using this model, we aimed to understand how the ErbB pathway functions in CLRM. <h3>Methods</h3> Lysates of fresh frozen CRLM samples from 18 patients who were chemonaive for CLRM were analysed using a proteomics-based assay Collaborative Enzyme Enhanced Reactive immunoassay (CEER) to quantify the phosphorylated and non-phosphorylated forms of ErbB family receptors and phosphorylated downstream ErbB pathway factors. We used a model of the EGFR signalling pathway previously developed by Birtwistle (2007) and validated using data from a breast cancer cell line to try and reproduce the activation patterns of HER1, HER2, and HER3. <h3>Results</h3> CRLM with high levels of both HER2 and HER3 were associated with high levels of phosphorylated HER3 (pHER3) and vice versa (p &lt; 0.001). A similar relationship was observed between pHER3 and HER1, HER2 (p &lt; 0.0001); and HER1, cMET (p = 0.006). Simulations focused on pHER3 for high and low levels of HER1, HER2, and HER3. The simulated relationship between pHER3 and HER1, HER2 was in good agreement with our observed data. High and low levels of both HER1, HER2 and HER1, HER3 also showed good agreement. Some discrepancy between simulation and experiment was found for high values of HER1 and low values of HER2 (and vice versa). <h3>Conclusion</h3> Simulations were performed to understand the dynamics of the EGFR pathway and showed partial agreement between the Birtwistle model and CEER data.The Birtwistle model which was designed to only capture the early network response to stimulation of ErbB receptors in breast cancer cells may not be directly applicable to resected CRLM. Further refinement of the model is required in the future. <h3>Disclosure of Interest</h3> None Declared