6,999 research outputs found

    Implicit Loss of Surjectivity and Facial Reduction: Theory and Applications

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    Facial reduction, pioneered by Borwein and Wolkowicz, is a preprocessing method that is commonly used to obtain strict feasibility in the reformulated, reduced constraint system. The importance of strict feasibility is often addressed in the context of the convergence results for interior point methods. Beyond the theoretical properties that the facial reduction conveys, we show that facial reduction, not only limited to interior point methods, leads to strong numerical performances in different classes of algorithms. In this thesis we study various consequences and the broad applicability of facial reduction. The thesis is organized in two parts. In the first part, we show the instabilities accompanied by the absence of strict feasibility through the lens of facially reduced systems. In particular, we exploit the implicit redundancies, revealed by each nontrivial facial reduction step, resulting in the implicit loss of surjectivity. This leads to the two-step facial reduction and two novel related notions of singularity. For the area of semidefinite programming, we use these singularities to strengthen a known bound on the solution rank, the Barvinok-Pataki bound. For the area of linear programming, we reveal degeneracies caused by the implicit redundancies. Furthermore, we propose a preprocessing tool that uses the simplex method. In the second part of this thesis, we continue with the semidefinite programs that do not have strictly feasible points. We focus on the doubly-nonnegative relaxation of the binary quadratic program and a semidefinite program with a nonlinear objective function. We closely work with two classes of algorithms, the splitting method and the Gauss-Newton interior point method. We elaborate on the advantages in building models from facial reduction. Moreover, we develop algorithms for real-world problems including the quadratic assignment problem, the protein side-chain positioning problem, and the key rate computation for quantum key distribution. Facial reduction continues to play an important role for providing robust reformulated models in both the theoretical and the practical aspects, resulting in successful numerical performances

    The Influence of Neuroendocrine and Genetic Markers of Stress on Cognitive Processing and Intrusive Symptoms

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    This body of research investigated the influence of neuroendocrine and genetic elements of arousal on cognitive processes in the development of intrusive memories and flash-forward intrusions as related to Post-Traumatic Stress Disorder. Specifically, this thesis investigated various mechanisms that may underlie intrusive symptoms as postulated by prevalent theories of PTSD. Study 1 examined the distinctive relationship between peritraumatic dissociation and subsequent re-experiencing symptoms. Network analyses revealed strong positive edges between peritraumatic dissociation and subsequent amnesia, as well as the re-experiencing symptoms of physical reactivity to reminders, flashbacks, intrusions, and dreams, and to a lesser extent emotional numbness and hypervigilance. The finding that peritraumatic dissociation is related to subsequent re-experiencing symptoms is consistent with cognitive models that emphasize the role of dissociative experiences during a traumatic event in the etiology of PTSD re-experiencing symptoms. Study 2 aimed to determine whether peri-traumatic stress, as measured via salivary cortisol and salivary alpha-amylase, as well as pre-existing genetic polymorphisms on the FKBP5 gene increased dissociation and data-driven processing, and subsequently impacted intrusive memories related to a trauma film. The findings revealed that greater noradrenergic arousal predicted less intrusive memory distress in individuals who scored higher on data-driven processing and trait dissociation, and in FKBP5 low-risk carriers. For individuals who reported less data-driven processing and trait dissociation, and in FKBP5 high-risk carriers, as noradrenergic arousal increased, intrusive memory distress increased. This study also showed no association between data-driven processing with memory fragmentation, and fragmentation with intrusive memories. Whilst these findings support some aspect of cognitive models of PTSD as they indicate a role for data-driven processing and dissociation in intrusive symptoms, they highlight a threshold at which these variables stop moderating the relationship between arousal and intrusive memories and suggest that memory fragmentation is not related to intrusive memories. Study 3 examined the role of cognitive control in flash-forward intrusions in the context of an enduring stressor, the COVID-19 pandemic. In line with expectations, results showed that as cognitive control worsened, FKBP5 high-risk carriers reported more flash-forward distress, and low-risk carriers reported less distress. These findings are considered in the context of hippocampal changes and are consistent with emerging theories of PTSD. Lastly, study 4 sought to investigate the role of two neurological processes, pattern separation and pattern completion in intrusive memories in individuals with PTSD compared to trauma exposed controls. Consistent with existing literature, the data indicate that individuals with PTSD reported more data-driven processing, more intrusive symptoms, and demonstrated better behavioural pattern completion than trauma-exposed controls. These findings are in line with current cognitive models of PTSD, as they again indicate a role for data-driven processing in PTSD. However, study 4 found no support for the postulate that deficient pattern separation is a feature of PTSD and found an opposite effect for the role of pattern completion. Whilst these findings are inconsistent with theory, they are in line with existing experimental studies. Overall, the findings from this thesis provide insight into cognitive and biological models of PTSD and shed light on the mechanisms underlying the nature and development of intrusive symptoms

    TeamSTEPPS and Organizational Culture

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    Patient safety issues remain despite several strategies developed for their deterrence. While many safety initiatives bring about improvement, they are repeatedly unsustainable and short-lived. The index hospital’s goal was to build an organizational culture within a groundwork that improves teamwork and continuing healthcare team engagement. Teamwork influences the efficiency of patient care, patient safety, and clinical outcomes, as it has been identified as an approach for enhancing collaboration, decreasing medical errors, and building a culture of safety in healthcare. The facility implemented Team Strategies and Tools to Enhance Performance and Patient Safety (TeamSTEPPS), an evidence-based framework which was used for team training to produce valuable and needed changes, facilitating modification of organizational culture, increasing patient safety compliance, or solving particular issues. This study aimed to identify the correlation between TeamSTEPPS enactment and improved organizational culture in the ambulatory care nursing department of a New York City public hospital

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

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    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

    Exploring cognitive mechanisms involved in self-face recognition

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    Due to the own face being a significant stimulus that is critical to one’s identity, the own face is suggested to be processed in a quantitatively different (i.e., faster and better recognition) and qualitatively different (i.e., processed in a more featural manner) manner compared to other faces. This thesis further explored the cognitive mechanisms (perceptual and attentional systems) involved in the processing of the own face. Chapter 2 explored the role of holistic and featural processing involved in the processing of self-face (and other faces) with eye-tracking measures in a passive-viewing paradigm and a face identification task. In the passive-viewing paradigm, the own face was sampled in a more featural manner compared to other faces whereas when asked to identify faces, all faces were sampled in a more holistic manner. Chapter 3 further explored the role of holistic and featural processing in the identification of the own face using the three standard measures of holistic face processing: The face inversion task, the composite face task, and the part-whole task. Compared to other faces, individuals showed a smaller “holistic interference” by a task irrelevant bottom half for the own face in the composite face task and a stronger feature advantage for the own face, but inversion impaired the identification of all faces. These findings suggest that self-face is processed in a more featural manner, but the findings do not deny the role of holistic processing. The final experimental chapter, Chapter 4, explored the modulation effects of cultural differences in one’s self-concept (i.e., independent vs. interdependent self-concept) and a negative self-concept (i.e., depressive traits) on the attentional prioritization for the own face with a visual search paradigm. Findings showed that the attentional prioritization for the own face over an unfamiliar face is not modulated by cultural differences of one’s self-concept nor one’s level of depressive traits, and individuals showed no difference in the attentional prioritization for both the own face and friend’s face, demonstrating no processing advantage for the own face over a personally familiar face. These findings suggests that the attentional prioritization for the own face is better explained by a familiar face advantage. Altogether, the findings of this thesis suggest that the own face is processed qualitatively different compared to both personally familiar and unfamiliar face, with the own face being processed in a more featural manner. However, in terms of quantitative differences, the self-face is processed differently compared to an unfamiliar face, but not to a familiar face. Although the specific face processing strategies for the own face may be due to the distinct visual experience that one has with their face, the attentional prioritization of the own face is however, better explained by a familiar face advantage rather than a self-specificity effect

    Scaling up integrated photonic reservoirs towards low-power high-bandwidth computing

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    Unsupervised inference methods for protein sequence data

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    L'abstract è presente nell'allegato / the abstract is in the attachmen

    Learning disentangled speech representations

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    A variety of informational factors are contained within the speech signal and a single short recording of speech reveals much more than the spoken words. The best method to extract and represent informational factors from the speech signal ultimately depends on which informational factors are desired and how they will be used. In addition, sometimes methods will capture more than one informational factor at the same time such as speaker identity, spoken content, and speaker prosody. The goal of this dissertation is to explore different ways to deconstruct the speech signal into abstract representations that can be learned and later reused in various speech technology tasks. This task of deconstructing, also known as disentanglement, is a form of distributed representation learning. As a general approach to disentanglement, there are some guiding principles that elaborate what a learned representation should contain as well as how it should function. In particular, learned representations should contain all of the requisite information in a more compact manner, be interpretable, remove nuisance factors of irrelevant information, be useful in downstream tasks, and independent of the task at hand. The learned representations should also be able to answer counter-factual questions. In some cases, learned speech representations can be re-assembled in different ways according to the requirements of downstream applications. For example, in a voice conversion task, the speech content is retained while the speaker identity is changed. And in a content-privacy task, some targeted content may be concealed without affecting how surrounding words sound. While there is no single-best method to disentangle all types of factors, some end-to-end approaches demonstrate a promising degree of generalization to diverse speech tasks. This thesis explores a variety of use-cases for disentangled representations including phone recognition, speaker diarization, linguistic code-switching, voice conversion, and content-based privacy masking. Speech representations can also be utilised for automatically assessing the quality and authenticity of speech, such as automatic MOS ratings or detecting deep fakes. The meaning of the term "disentanglement" is not well defined in previous work, and it has acquired several meanings depending on the domain (e.g. image vs. speech). Sometimes the term "disentanglement" is used interchangeably with the term "factorization". This thesis proposes that disentanglement of speech is distinct, and offers a viewpoint of disentanglement that can be considered both theoretically and practically
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