428 research outputs found

    Memory management techniques for large-scale persistent-main-memory systems

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    Storage Class Memory (SCM) is a novel class of memory technologies that promise to revolutionize database architectures. SCM is byte-addressable and exhibits latencies similar to those of DRAM, while being non-volatile. Hence, SCM could replace both main memory and storage, enabling a novel single-level database architecture without the traditional I/O bottleneck. Fail-safe persistent SCM allocation can be considered conditio sine qua non for enabling this novel architecture paradigm for database management systems. In this paper we present PAllocator, a fail-safe persistent SCM allocator whose design emphasizes high concurrency and capacity scalability. Contrary to previous works, PAllocator thoroughly addresses the important challenge of persistent memory fragmentation by implementing an efficient defragmentation algorithm. We show that PAllocator outperforms state-of-the-art persistent allocators by up to one order of magnitude, both in operation throughput and recovery time, and enables up to 2.39x higher operation throughput on a persistent B-Tree

    Reflexion: Language Agents with Verbal Reinforcement Learning

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    Large language models (LLMs) have been increasingly used to interact with external environments (e.g., games, compilers, APIs) as goal-driven agents. However, it remains challenging for these language agents to quickly and efficiently learn from trial-and-error as traditional reinforcement learning methods require extensive training samples and expensive model fine-tuning. We propose Reflexion, a novel framework to reinforce language agents not by updating weights, but instead through linguistic feedback. Concretely, Reflexion agents verbally reflect on task feedback signals, then maintain their own reflective text in an episodic memory buffer to induce better decision-making in subsequent trials. Reflexion is flexible enough to incorporate various types (scalar values or free-form language) and sources (external or internally simulated) of feedback signals, and obtains significant improvements over a baseline agent across diverse tasks (sequential decision-making, coding, language reasoning). For example, Reflexion achieves a 91% pass@1 accuracy on the HumanEval coding benchmark, surpassing the previous state-of-the-art GPT-4 that achieves 80%. We also conduct ablation and analysis studies using different feedback signals, feedback incorporation methods, and agent types, and provide insights into how they affect performance.Comment: v4 contains a few additional experiment

    Ekologické a evoluční procesy určující strukturu sítí rostlin a opylovačů

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    Abtrakt Rozmnožování většiny druhů rostlin a potrava značné části diverzity živočichů na této planetě přímo závisí na vztazích mezi květy a opylovači. Donedávna se však převážná většina výzkumu opylování zaměřovala pouze na studium opylování konkrétních rostlin a jen málo pozornosti bylo věnováno celým společenstvům rostlin i opylovačů. V posledních desetiletích se však zaměření ekologie opylování posunulo díky zavedení konceptu opylovacích sítí. Tento koncept umožnil zabývat se opylováním v kontextu celého společenstva, poukázal na rozmanitost i komplexitu vztahů mezi rostlinami a jejich opylovači a otevřel řadu nových možností výzkumu těchto vztahů z pohledu jeho významu pro živočichy nebo z pohledu časové a prostorové dynamiky opylovacích interakcí. Přesto však dosud máme jen matné představy o tom, jaké procesy jsou zodpovědné za strukturu a dynamiku těchto sítí. Podoba opylovací sítě je formována jak ekologickými, tak evolučními procesy. Z ekologického pohledu hraje roli například to, jak se druhy v čase a prostoru potkávají nebo jak si jednotlivé taxony opylovačů vybírají mezi rostlinami v závislosti na kontextu prostředí, aktuálních potravních potřebách či nabídce květních zdrojů. Z evolučního pohledu je pak podoba sítě vztahů mezi rostlinami a opylovači určena tím, jak se druhy na sebe vzájemně...Associations between flowers and pollinators are responsible for reproduction of majority of plant species as well as food supply for substantial part of animal diversity on the Earth. Until recently, the studies on plant-pollinator relationship were focused predominantly on pollination of particular plant species, with only little or no accent on community perspective. In recent decades, however, pollination ecology shifted its focus rather to community context by introducing so called pollination networks. This approach allows us to view the ubiquity and complexity of the interactions between plants and their pollinators and it opened up many new opportunities to study the pollination from animal perspective or to access spatio-temporal variability in the interactions. However, we still have only limited insight into the processes driving the structure and dynamics of such networks. The assembly of plants, pollinators and their interactions are driven by various ecological as well as evolutionary processes. From the ecological point of view, species co-occurrence in time and space may affect the interactions, or species flexibility for various community contexts providing different food sources may play role. In the evolutionary perspective, species may have various co-adaptations due to their...Katedra zoologieDepartment of ZoologyPřírodovědecká fakultaFaculty of Scienc

    An integrated computational and collaborative approach for city resilience planning

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    Given the rise in climate change-related extreme events, there is an urgent need for cities and regions to implement resilience plans based on data and evidence and developed in collaboration with key stakeholders. However, current planning and decision-making processes rely on limited data and modelling. Moreover, stakeholder engagement is significantly inhibited by social, political, and technological barriers. The research presented in this thesis aims to enhance resilience planning practice through the development and evaluation of an integrated computational and collaborative scenario planning approach. The scenario planning approach is tested within a geodesign framework and supported by several planning support systems (PSS), including urban growth models. These PSS tools are made accessible to key stakeholders through dedicated planning support theatres, enabling participants to collaborate both in-person and online. Through two empirical case studies conducted in Australian regions, this research integrates data-driven modelling (computational) with people-led geodesign (collaborative) approaches for scenario forecasting and planning. The first case study explores anticipatory/normative scenarios, while the second focuses on exploratory scenario planning, with both aiming to enhance city and regional resilience. This thesis examines the roles played by both simple digital tools and purpose-built planning support theatres in scenario planning processes with key stakeholders. The research investigates the utility of data-driven models in supporting collaborative scenario planning. Both integration experiments received positive feedback from most participants. However, to truly improve the process, there is a need for widely available high-quality spatial and temporal datasets, including localised climate change impact data. In summary, an integrated computational and collaborative approach, augmented by data and technology, can provide an evidence base for decision-making towards a resilient future, fostering deeper engagement of the local community and across-government collaboration in scenario planning

    2023-2024 Lindenwood University Undergraduate Course Catalog

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    Lindenwood University Undergraduate Course Catalog.https://digitalcommons.lindenwood.edu/catalogs/1209/thumbnail.jp

    Investigating modifiers that can regulate selective vulnerability in mouse models of spinal muscular atrophy

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    Spinal muscular atrophy (SMA) is a childhood form of motor neuron disease. It is characterised by the loss of lower motor neurons and muscle weakening and atrophy of associated muscles. Motor neurons (MNs) are the primary pathological target of SMA, but it has long been shown that breakdown of neuromuscular junctions (NMJs) is also an early pathological target of the disease. However, not all MNs are equally vulnerable, with some being lost very early in the course of the disease, whilst other subpopulations are consistently spared until late stages of the disease. This selective vulnerability of MNs is a well-known pathological hallmark of SMA, however the underlying molecular mechanisms of it are yet unknown. The work contained within this thesis aims to investigate the basis of selective vulnerability, which will give critical insight into the factors which drive motor neuron pathology and help identify novel neuroprotective strategies. Selective vulnerability of MNs and a wide range of muscles has been reported in SMA patients and in commonly utilised mouse models of SMA. Despite the many publications in each mouse model of SMA, there has not yet been a comparison of NMJ pathology across different mouse models of SMA. I therefore performed an extensive analysis of NMJ pathology in 20 muscles from the Smn²ᴮ/⁻ mouse model of SMA and subsequently compared pattern of selective vulnerability between other mouse models of SMA. This revealed a more profound motor neuron cell body loss in thoracic and upper lumbar spinal cord segments and higher levels of NMJ loss in muscles innervated by nerves from these spinal cord segments in the Smn²ᴮ/⁻ mouse model. Comparison of selective vulnerability patterns between the Smn²ᴮ/⁻ mouse model and other mouse models of SMA, showed that all models had a distinct pattern of selective vulnerability, with the Smn²ᴮ/⁻ showing most similarity to patients. Patterns of vulnerability could not be attributed to developmental subtype or muscle fibre type in any of the mouse models. To gain insight into the molecular mechanisms regulating selective vulnerability, I performed cross-model transcriptional analysis. Here, my goal was to analyse published RNA-seq data sets to look for novel modifiers. I obtained RNA-seq data sets from laser capture microdissection (LCM) motor neurons from both SMNΔ7 and Smn²ᴮ/⁻ mice, from a range of resistant and vulnerable populations. I reanalysed and compared these data sets and identified a number of exciting potential modifiers. In particular, pituitary adenylate cyclase-activating polypeptide (PACAP), seemed to be an exciting potential neuroprotective modifier. PACAP has been shown to be neuroprotective in an array of neurodegenerative diseases but has not yet been investigated in models of SMA. Here, I investigated whether increased PACAP levels could ameliorate neuronal pathology in a mouse model of SMA. Firstly, PACAP was administered IP to the Smn²ᴮ/⁻ mouse model, showing no significant effect on survival, motor performance and selective vulnerability. Therefore, subsequently PACAP was administered via AAV9 delivery in the Smn²ᴮ/⁻ mouse model, showing no significant effects on the neuropathology in the Smn²ᴮ/⁻ mouse model. Finally, since I have identified significant divergence in relative vulnerability in the neurons of the facial motor nucleus, I aimed to perform high spatial resolution transcriptional profiling of motor neurons in the SMNΔ7 mouse model with the ultimate goal of identifying transcriptional signatures of differential vulnerability. I therefore optimised and applied a novel method to perform RNA sequencing on single MNs isolated from the facial nucleus of the brainstem by LCM. A total of 1050 single MNs have been isolated from the facial nucleus from individual P2, P5 and P9 SMNΔ7 mice and respective controls. cDNA libraries were prepared and cDNA fragmented, uniquely barcoded and sent for initial quality control RNA-seq analysis. The analysis revealed promising quality control parameters of the sequenced samples and thereby confirmed a successful optimisation of this novel sequencing technique. Overall, these results provide an important insight into selective vulnerability patterns of different SMA mouse models and identified novel mechanisms and transcripts that have the potential to contribute to the protection of motor neurons in SMA mouse models

    Persistent Memory File Systems:A Survey

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    Persistent Memory (PM) is non-volatile byte-addressable memory that offers read and write latencies in the order of magnitude smaller than flash storage, such as SSDs. This survey discusses how file systems address the most prominent challenges in the implementation of file systems for Persistent Memory. First, we discuss how the properties of Persistent Memory change file system design. Second, we discuss work that aims to optimize small file I/O and the associated meta-data resolution. Third, we address how existing Persistent Memory file systems achieve (meta) data persistence and consistency

    Bacterium of one thousand and one variants: genetic diversity of Neisseria gonorrhoeae pathogenicity

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    The bacterium Neisseria gonorrhoeae causes the sexually transmitted infection gonorrhoea. Although diverse clinical manifestations are associated with gonorrhoea, ranging from asymptomatic through to localized and disseminated infection, very little is known about the bacterial determinants implicated in causing such different clinical symptoms. In particular, virulence factors, although defined and investigated in particular strains, often lack comprehensive analysis of their genetic diversity and how this relates to particular disease states. This review examines the clinical manifestations of gonorrhoea and discusses them in relation to disease severity and association with expression of particular virulence factors including PorB, lipooligosaccharide (LOS) and Opa, both in terms of their mechanisms of action and inter- and intra-strain variation. Particular attention is paid to phase variation as a key mechanism of genetic variation in the gonococcus and the impact of this during infection. We describe how whole-genome-sequence-based approaches that focus on virulence factors can be employed for vaccine development and discuss whether whole-genome-sequence data can be used to predict the severity of gonococcal infection

    Differential evolution of non-coding DNA across eukaryotes and its close relationship with complex multicellularity on Earth

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    Here, I elaborate on the hypothesis that complex multicellularity (CM, sensu Knoll) is a major evolutionary transition (sensu Szathmary), which has convergently evolved a few times in Eukarya only: within red and brown algae, plants, animals, and fungi. Paradoxically, CM seems to correlate with the expansion of non-coding DNA (ncDNA) in the genome rather than with genome size or the total number of genes. Thus, I investigated the correlation between genome and organismal complexities across 461 eukaryotes under a phylogenetically controlled framework. To that end, I introduce the first formal definitions and criteria to distinguish ‘unicellularity’, ‘simple’ (SM) and ‘complex’ multicellularity. Rather than using the limited available estimations of unique cell types, the 461 species were classified according to our criteria by reviewing their life cycle and body plan development from literature. Then, I investigated the evolutionary association between genome size and 35 genome-wide features (introns and exons from protein-coding genes, repeats and intergenic regions) describing the coding and ncDNA complexities of the 461 genomes. To that end, I developed ‘GenomeContent’, a program that systematically retrieves massive multidimensional datasets from gene annotations and calculates over 100 genome-wide statistics. R-scripts coupled to parallel computing were created to calculate >260,000 phylogenetic controlled pairwise correlations. As previously reported, both repetitive and non-repetitive DNA are found to be scaling strongly and positively with genome size across most eukaryotic lineages. Contrasting previous studies, I demonstrate that changes in the length and repeat composition of introns are only weakly or moderately associated with changes in genome size at the global phylogenetic scale, while changes in intron abundance (within and across genes) are either not or only very weakly associated with changes in genome size. Our evolutionary correlations are robust to: different phylogenetic regression methods, uncertainties in the tree of eukaryotes, variations in genome size estimates, and randomly reduced datasets. Then, I investigated the correlation between the 35 genome-wide features and the cellular complexity of the 461 eukaryotes with phylogenetic Principal Component Analyses. Our results endorse a genetic distinction between SM and CM in Archaeplastida and Metazoa, but not so clearly in Fungi. Remarkably, complex multicellular organisms and their closest ancestral relatives are characterized by high intron-richness, regardless of genome size. Finally, I argue why and how a vast expansion of non-coding RNA (ncRNA) regulators rather than of novel protein regulators can promote the emergence of CM in Eukarya. As a proof of concept, I co-developed a novel ‘ceRNA-motif pipeline’ for the prediction of “competing endogenous” ncRNAs (ceRNAs) that regulate microRNAs in plants. We identified three candidate ceRNAs motifs: MIM166, MIM171 and MIM159/319, which were found to be conserved across land plants and be potentially involved in diverse developmental processes and stress responses. Collectively, the findings of this dissertation support our hypothesis that CM on Earth is a major evolutionary transition promoted by the expansion of two major ncDNA classes, introns and regulatory ncRNAs, which might have boosted the irreversible commitment of cell types in certain lineages by canalizing the timing and kinetics of the eukaryotic transcriptome.:Cover page Abstract Acknowledgements Index 1. The structure of this thesis 1.1. Structure of this PhD dissertation 1.2. Publications of this PhD dissertation 1.3. Computational infrastructure and resources 1.4. Disclosure of financial support and information use 1.5. Acknowledgements 1.6. Author contributions and use of impersonal and personal pronouns 2. Biological background 2.1. The complexity of the eukaryotic genome 2.2. The problem of counting and defining “genes” in eukaryotes 2.3. The “function” concept for genes and “dark matter” 2.4. Increases of organismal complexity on Earth through multicellularity 2.5. Multicellularity is a “fitness transition” in individuality 2.6. The complexity of cell differentiation in multicellularity 3. Technical background 3.1. The Phylogenetic Comparative Method (PCM) 3.2. RNA secondary structure prediction 3.3. Some standards for genome and gene annotation 4. What is in a eukaryotic genome? GenomeContent provides a good answer 4.1. Background 4.2. Motivation: an interoperable tool for data retrieval of gene annotations 4.3. Methods 4.4. Results 4.5. Discussion 5. The evolutionary correlation between genome size and ncDNA 5.1. Background 5.2. Motivation: estimating the relationship between genome size and ncDNA 5.3. Methods 5.4. Results 5.5. Discussion 6. The relationship between non-coding DNA and Complex Multicellularity 6.1. Background 6.2. Motivation: How to define and measure complex multicellularity across eukaryotes? 6.3. Methods 6.4. Results 6.5. Discussion 7. The ceRNA motif pipeline: regulation of microRNAs by target mimics 7.1. Background 7.2. A revisited protocol for the computational analysis of Target Mimics 7.3. Motivation: a novel pipeline for ceRNA motif discovery 7.4. Methods 7.5. Results 7.6. Discussion 8. Conclusions and outlook 8.1. Contributions and lessons for the bioinformatics of large-scale comparative analyses 8.2. Intron features are evolutionarily decoupled among themselves and from genome size throughout Eukarya 8.3. “Complex multicellularity” is a major evolutionary transition 8.4. Role of RNA throughout the evolution of life and complex multicellularity on Earth 9. Supplementary Data Bibliography Curriculum Scientiae Selbständigkeitserklärung (declaration of authorship

    Ekologické a evoluční procesy určující strukturu sítí rostlin a opylovačů

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    Associations between flowers and pollinators are responsible for reproduction of majority of plant species as well as food supply for substantial part of animal diversity on the Earth. Until recently, the studies on plant-pollinator relationship were focused predominantly on pollination of particular plant species, with only little or no accent on community perspective. In recent decades, however, pollination ecology shifted its focus rather to community context by introducing so called pollination networks. This approach allows us to view the ubiquity and complexity of the interactions between plants and their pollinators and it opened up many new opportunities to study the pollination from animal perspective or to access spatio-temporal variability in the interactions. However, we still have only limited insight into the processes driving the structure and dynamics of such networks. The assembly of plants, pollinators and their interactions are driven by various ecological as well as evolutionary processes. From the ecological point of view, species co-occurrence in time and space may affect the interactions, or species flexibility for various community contexts providing different food sources may play role. In the evolutionary perspective, species may have various co-adaptations due to their...Abtrakt Rozmnožování většiny druhů rostlin a potrava značné části diverzity živočichů na této planetě přímo závisí na vztazích mezi květy a opylovači. Donedávna se však převážná většina výzkumu opylování zaměřovala pouze na studium opylování konkrétních rostlin a jen málo pozornosti bylo věnováno celým společenstvům rostlin i opylovačů. V posledních desetiletích se však zaměření ekologie opylování posunulo díky zavedení konceptu opylovacích sítí. Tento koncept umožnil zabývat se opylováním v kontextu celého společenstva, poukázal na rozmanitost i komplexitu vztahů mezi rostlinami a jejich opylovači a otevřel řadu nových možností výzkumu těchto vztahů z pohledu jeho významu pro živočichy nebo z pohledu časové a prostorové dynamiky opylovacích interakcí. Přesto však dosud máme jen matné představy o tom, jaké procesy jsou zodpovědné za strukturu a dynamiku těchto sítí. Podoba opylovací sítě je formována jak ekologickými, tak evolučními procesy. Z ekologického pohledu hraje roli například to, jak se druhy v čase a prostoru potkávají nebo jak si jednotlivé taxony opylovačů vybírají mezi rostlinami v závislosti na kontextu prostředí, aktuálních potravních potřebách či nabídce květních zdrojů. Z evolučního pohledu je pak podoba sítě vztahů mezi rostlinami a opylovači určena tím, jak se druhy na sebe vzájemně...Katedra zoologieDepartment of ZoologyFaculty of SciencePřírodovědecká fakult
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