6,053 research outputs found

    UMSL Bulletin 2023-2024

    Get PDF
    The 2023-2024 Bulletin and Course Catalog for the University of Missouri St. Louis.https://irl.umsl.edu/bulletin/1088/thumbnail.jp

    Graduate Catalog of Studies, 2023-2024

    Get PDF

    Current Challenges and Advances in Cataract Surgery

    Get PDF
    This reprint focuses on new trials related to cataract surgery, intraocular lens power calculations for cataracts after refractive surgery, problems related to high myopia, toric IOL power calculations, etc. Intraoperative use of the 3D Viewing System and OCT, studies on the spectacle dependence of EDOF, IOL fixation status and visual function, and dry eye after FLAC are also discussed. Proteomic analysis of aqueous humor proteins is also discussed

    UMSL Bulletin 2022-2023

    Get PDF
    The 2022-2023 Bulletin and Course Catalog for the University of Missouri St. Louis.https://irl.umsl.edu/bulletin/1087/thumbnail.jp

    Using machine learning to predict pathogenicity of genomic variants throughout the human genome

    Get PDF
    Geschätzt mehr als 6.000 Erkrankungen werden durch Veränderungen im Genom verursacht. Ursachen gibt es viele: Eine genomische Variante kann die Translation eines Proteins stoppen, die Genregulation stören oder das Spleißen der mRNA in eine andere Isoform begünstigen. All diese Prozesse müssen überprüft werden, um die zum beschriebenen Phänotyp passende Variante zu ermitteln. Eine Automatisierung dieses Prozesses sind Varianteneffektmodelle. Mittels maschinellem Lernen und Annotationen aus verschiedenen Quellen bewerten diese Modelle genomische Varianten hinsichtlich ihrer Pathogenität. Die Entwicklung eines Varianteneffektmodells erfordert eine Reihe von Schritten: Annotation der Trainingsdaten, Auswahl von Features, Training verschiedener Modelle und Selektion eines Modells. Hier präsentiere ich ein allgemeines Workflow dieses Prozesses. Dieses ermöglicht es den Prozess zu konfigurieren, Modellmerkmale zu bearbeiten, und verschiedene Annotationen zu testen. Der Workflow umfasst außerdem die Optimierung von Hyperparametern, Validierung und letztlich die Anwendung des Modells durch genomweites Berechnen von Varianten-Scores. Der Workflow wird in der Entwicklung von Combined Annotation Dependent Depletion (CADD), einem Varianteneffektmodell zur genomweiten Bewertung von SNVs und InDels, verwendet. Durch Etablierung des ersten Varianteneffektmodells für das humane Referenzgenome GRCh38 demonstriere ich die gewonnenen Möglichkeiten Annotationen aufzugreifen und neue Modelle zu trainieren. Außerdem zeige ich, wie Deep-Learning-Scores als Feature in einem CADD-Modell die Vorhersage von RNA-Spleißing verbessern. Außerdem werden Varianteneffektmodelle aufgrund eines neuen, auf Allelhäufigkeit basierten, Trainingsdatensatz entwickelt. Diese Ergebnisse zeigen, dass der entwickelte Workflow eine skalierbare und flexible Möglichkeit ist, um Varianteneffektmodelle zu entwickeln. Alle entstandenen Scores sind unter cadd.gs.washington.edu und cadd.bihealth.org frei verfügbar.More than 6,000 diseases are estimated to be caused by genomic variants. This can happen in many possible ways: a variant may stop the translation of a protein, interfere with gene regulation, or alter splicing of the transcribed mRNA into an unwanted isoform. It is necessary to investigate all of these processes in order to evaluate which variant may be causal for the deleterious phenotype. A great help in this regard are variant effect scores. Implemented as machine learning classifiers, they integrate annotations from different resources to rank genomic variants in terms of pathogenicity. Developing a variant effect score requires multiple steps: annotation of the training data, feature selection, model training, benchmarking, and finally deployment for the model's application. Here, I present a generalized workflow of this process. It makes it simple to configure how information is converted into model features, enabling the rapid exploration of different annotations. The workflow further implements hyperparameter optimization, model validation and ultimately deployment of a selected model via genome-wide scoring of genomic variants. The workflow is applied to train Combined Annotation Dependent Depletion (CADD), a variant effect model that is scoring SNVs and InDels genome-wide. I show that the workflow can be quickly adapted to novel annotations by porting CADD to the genome reference GRCh38. Further, I demonstrate the integration of deep-neural network scores as features into a new CADD model, improving the annotation of RNA splicing events. Finally, I apply the workflow to train multiple variant effect models from training data that is based on variants selected by allele frequency. In conclusion, the developed workflow presents a flexible and scalable method to train variant effect scores. All software and developed scores are freely available from cadd.gs.washington.edu and cadd.bihealth.org

    Science and Innovations for Food Systems Transformation

    Get PDF
    This Open Access book compiles the findings of the Scientific Group of the United Nations Food Systems Summit 2021 and its research partners. The Scientific Group was an independent group of 28 food systems scientists from all over the world with a mandate from the Deputy Secretary-General of the United Nations. The chapters provide science- and research-based, state-of-the-art, solution-oriented knowledge and evidence to inform the transformation of contemporary food systems in order to achieve more sustainable, equitable and resilient systems

    Characterising Shape Variation in the Human Right Ventricle Using Statistical Shape Analysis: Preliminary Outcomes and Potential for Predicting Hypertension in a Clinical Setting

    Get PDF
    Variations in the shape of the human right ventricle (RV) have previously been shown to be predictive of heart function and long term prognosis in Pulmonary Hypertension (PH), a deadly disease characterised by high blood pressure in the pulmonary arteries. The extent to which ventricular shape is also affected by non-pathological features such as sex, body mass index (BMI) and age is explored in this thesis. If fundamental differences in the shape of a structurally normal RV exist, these might also impact the success of a predictive model. This thesis evaluates the extent to which non-pathological features affect the shape of the RV and determines the best ways, in terms of procedure and analysis, to adapt the model to consistently predict PH. It also identifies areas where the statistical shape analysis procedure is robust, and considers the extent to which specific, non-pathological, characteristics impact the diagnostic potential of the statistical shape model. Finally, recommendations are made on next steps in the development of a classification procedure for PH. The dataset was composed of clinically-obtained, cardiovascular magnetic resonance images (CMR) from two independent sources; The University of Pittsburgh Medical Center and Newcastle University. Shape change is assessed using a 3D statistical shape analysis technique, which topologically maps heart meshes through an harmonic mapping approach to create a unique shape function for each shape. Proper Orthogonal Decomposition (POD) was applied to the complete set of shape functions in order to determine and rank a set of shape features (i.e. modes and corresponding coefficients from the decomposition). MRI scanning protocol produced the most significant difference in shape; a shape mode associated with detail at the RV apex and ventricular length from apex to base strongly correlated with the MRI sequence used to record each subject. Qualitatively, a protocol which skipped slices produced a shorter RV with less detail at the apex. Decomposition of sex, age and BMI also derives unique RV shape descriptors which correspond to anatomically meaningful features. The shape features are shown to be able to predict presence of PH. The predictive model can be improved by including BMI as a factor, but these improvements are mainly concentrated in identification of healthy subjects

    Combining Metabolic Engineering and Synthetic Biology Approaches for the Production of Abscisic Acid in Yeast

    Get PDF
    Nature presents us with a myriad of complex and diverse molecules. Many of these molecules prove to be useful to humans and find applications as pharmaceuticals, biofuels, agrochemicals, cosmetic ingredients or food additives. One highly promising natural product with a broad range of potential applications is the terpenoid abscisic acid (ABA). ABA fulfils a pivotal role in higher plants by regulating various developmental processes as well as abiotic stress responses. However, ABA is also produced in many other organisms, including humans. It appears to be a ubiquitous and evolutionary conserved signalling molecule throughout nature. Genetically engineered microorganisms, referred to as microbial cell factories, can be a sustainable source of natural products. In this thesis, a cell factory for the heterologous production of ABA was established and optimized employing the yeast Saccharomyces cerevisiae. Cell factory development is an inherently time-consuming process. As an enabling technology for subsequent work on the ABA cell factory, we expanded the modular cloning toolkit for yeast and made it more applicable for common genetic engineering tasks (Paper I). The ABA biosynthetic pathway of Botrytis cinerea was used to construct an ABA-producing S. cerevisiae strain (Paper II). The activity of two B. cinerea proteins, BcABA1 and BcABA2, was found to limit ABA titers. Two optimization approaches were devised for the following studies. Firstly, various rational engineering targets were explored, of which the native yeast gene PAH1 was identified as the most promising candidate (Paper III). Knockdown of PAH1 benefited ABA production without affecting growth. Secondly, platform strains for screening BcABA1 and BcABA2 enzyme libraries were developed, which utilize an ABA biosensor and enable a high throughput screening approach (Paper IV). In this work, we combined metabolic engineering and synthetic biology approaches for the heterologous production of ABA, and furthermore provided tools and insights that will be useful beyond the scope of this project
    • …
    corecore