5,609 research outputs found

    Towards A Practical High-Assurance Systems Programming Language

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    Writing correct and performant low-level systems code is a notoriously demanding job, even for experienced developers. To make the matter worse, formally reasoning about their correctness properties introduces yet another level of complexity to the task. It requires considerable expertise in both systems programming and formal verification. The development can be extremely costly due to the sheer complexity of the systems and the nuances in them, if not assisted with appropriate tools that provide abstraction and automation. Cogent is designed to alleviate the burden on developers when writing and verifying systems code. It is a high-level functional language with a certifying compiler, which automatically proves the correctness of the compiled code and also provides a purely functional abstraction of the low-level program to the developer. Equational reasoning techniques can then be used to prove functional correctness properties of the program on top of this abstract semantics, which is notably less laborious than directly verifying the C code. To make Cogent a more approachable and effective tool for developing real-world systems, we further strengthen the framework by extending the core language and its ecosystem. Specifically, we enrich the language to allow users to control the memory representation of algebraic data types, while retaining the automatic proof with a data layout refinement calculus. We repurpose existing tools in a novel way and develop an intuitive foreign function interface, which provides users a seamless experience when using Cogent in conjunction with native C. We augment the Cogent ecosystem with a property-based testing framework, which helps developers better understand the impact formal verification has on their programs and enables a progressive approach to producing high-assurance systems. Finally we explore refinement type systems, which we plan to incorporate into Cogent for more expressiveness and better integration of systems programmers with the verification process

    Multipartite entanglement groups

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    We propose to define multipartite entanglement of pure states as transformations acting on some parts of a system that can be undone by transformations acting on other parts. This leads to a definition of multipartite entanglement in terms of groups, namely certain quotients of the stabilizer group and its subgroups. We analyze properties of these entanglement groups and show that they lead to restrictions which give a precise meaning to monogamy of entanglement. We use these groups to propose a finite classification of entanglement types in multi-partite quantum systems and we show that this characterization of entanglement underlies several well-known quantum tasks.Comment: 36 page

    TEMPERATURE REGULATION OF PIPECOLIC ACID-MEDIATED PLANT SYSTEMIC IMMUNITY IN ARABIDOPSIS THALIANA

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    Significant crop losses are caused by pathogenic infections annually, which are exacerbated by increasing global temperatures due to climate change. One way by which plants respond to pathogenic attacks is through the activation of pattern-triggered immunity (PTI), effector-triggered immunity (ETI), and systemic acquired resistance (SAR), which lead to production of the central defence phytohormone salicylic acid (SA). Accompanying SA release is the putative mobilization of pipecolic acid (Pip), which acts as an immune regulatory plant metabolite that works with and independently from SA. As demonstrated in the model plant Arabidopsis thaliana following infection with the model bacterial pathogen Pseudomonas syringae pv. tomato (Pst) DC3000, Pip and its hydroxylated derivative N-hydroxypipecolic acid (NHP) accumulate in local and distal tissues to amplify the plant immune response and prime the plant for future infections. Previous studies have only shown that increased temperature negatively impact PTI, ETI and SA production in the local/primary sites of infection. However, how temperature affects plant systemic immunity has not been fully explored. In this thesis, I showed that systemic immunity in Arabidopsis to Pst DC3000 was significantly reduced at elevated temperatures. Elevated temperature decreased expression of the SAR-associated Pip-NHP biosynthetic genes AGD2-LIKE DEFENSE RESPONSE PROTEIN 1 (ALD1) and FLAVIN-DEPENDENT MONOOXYGENASE 1 (FMO1) in systemically primed leaf tissues. Remarkably, exogenous Pip application via local leaf infiltration or root-drench restored immunity to Pst DC3000 at elevated temperature; however, local leaf infiltration did not restore immunity in systemic leaves. I have also shown how Pip-induced gene expression locally and systemically were affected by temperature. Finally, because of the interlinked regulation between SA and Pip/NHP by the master transcription factor CAM-BINDING PROTEIN 60-LIKE G (CBP60g), I have shown that Arabidopsis plants constitutively expressing CBP60g (35S:CBP60g) exhibited SAR at both normal and elevated temperatures. My results suggest that CBP60g controls the temperature-sensitivity of plant systemic immunity by modulating NHP biosynthesis. Overall, this thesis contributes to understanding the signaling pathways regulating local and systemic plant immune responses in our warming climate

    Applications and Properties of Magnetic Nanoparticles

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    This Special Issue aimed to cover the new developments in the synthesis and characterization of magnetic nanoconstructs ranging from conventional metal oxide nanoparticles to novel molecule-based or hybrid multifunctional nano-objects. At the same time, the focus was on the potential of these novel magnetic nanoconstructs in several possible applications, e.g. sensing, energy storage, and nanomedicine

    Syndecan-4 Mediates the Cellular Entry of Adeno-Associated Virus 9

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    Due to their low pathogenicity, immunogenicity, and long-term gene expression, adeno-associated virus (AAV) vectors emerged as safe and efficient gene delivery tools, over-coming setbacks experienced with other viral gene delivery systems in early gene therapy trials. Among AAVs, AAV9 can translocate through the blood-brain barrier (BBB), making it a promising gene delivery tool for transducing the central nervous system (CNS) via systemic administration. Recent reports on the shortcomings of AAV9-mediated gene delivery into the CNS require reviewing the molecular base of AAV9 cellular biology. A more detailed understanding of AAV9’s cellular entry would eradicate current hurdles and enable more efficient AAV9-based gene therapy approaches. Syndecans, the transmembrane family of heparan-sulfate proteoglycans, facilitate the cellular uptake of various viruses and drug delivery systems. Utilizing human cell lines and syndecan-specific cellular assays, we assessed the involvement of syndecans in AAV9’s cellular entry. The ubiquitously expressed isoform, syndecan-4 proved its superiority in facilitating AAV9 internalization among syndecans. Introducing syndecan-4 into poorly transducible cell lines enabled robust AAV9-dependent gene transduction, while its knockdown reduced AAV9’s cellular entry. Attachment of AAV9 to syndecan-4 is mediated not just by the polyanionic heparan-sulfate chains but also by the cell-binding domain of the extracellular syndecan-4 core protein. Co-immunoprecipitation assays and affinity proteomics also confirmed the role of syndecan-4 in the cellular entry of AAV9. Overall, our findings highlight the universally expressed syndecan-4 as a significant contributor to the cellular internalization of AAV9 and provide a molecular-based, rational explanation for the low gene delivery potential of AAV9 into the CNS

    Histopathologic and proteogenomic heterogeneity reveals features of clear cell renal cell carcinoma aggressiveness

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    Clear cell renal cell carcinomas (ccRCCs) represent ∼75% of RCC cases and account for most RCC-associated deaths. Inter- and intratumoral heterogeneity (ITH) results in varying prognosis and treatment outcomes. To obtain the most comprehensive profile of ccRCC, we perform integrative histopathologic, proteogenomic, and metabolomic analyses on 305 ccRCC tumor segments and 166 paired adjacent normal tissues from 213 cases. Combining histologic and molecular profiles reveals ITH in 90% of ccRCCs, with 50% demonstrating immune signature heterogeneity. High tumor grade, along with BAP1 mutation, genome instability, increased hypermethylation, and a specific protein glycosylation signature define a high-risk disease subset, where UCHL1 expression displays prognostic value. Single-nuclei RNA sequencing of the adverse sarcomatoid and rhabdoid phenotypes uncover gene signatures and potential insights into tumor evolution. In vitro cell line studies confirm the potential of inhibiting identified phosphoproteome targets. This study molecularly stratifies aggressive histopathologic subtypes that may inform more effective treatment strategies

    Cyberbullying in educational context

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    Kustenmacher and Seiwert (2004) explain a man’s inclination to resort to technology in his interaction with the environment and society. Thus, the solution to the negative consequences of Cyberbullying in a technologically dominated society is represented by technology as part of the technological paradox (Tugui, 2009), in which man has a dual role, both slave and master, in the interaction with it. In this respect, it is noted that, notably after 2010, there have been many attempts to involve artificial intelligence (AI) to recognize, identify, limit or avoid the manifestation of aggressive behaviours of the CBB type. For an overview of the use of artificial intelligence in solving various problems related to CBB, we extracted works from the Scopus database that respond to the criterion of the existence of the words “cyberbullying” and “artificial intelligence” in the Title, Keywords and Abstract. These articles were the subject of the content analysis of the title and, subsequently, only those that are identified as a solution in the process of recognizing, identifying, limiting or avoiding the manifestation of CBB were kept in the following Table where we have these data synthesized and organized by years

    Pediatric and Adolescent Nephrology Facing the Future: Diagnostic Advances and Prognostic Biomarkers in Everyday Practice

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    The Special Issue entitled “Pediatric and adolescent nephrology facing the future: diagnostic advances and prognostic biomarkers in everyday practice” contains articles written in the era when COVID-19 had not yet been a major clinical problem in children. Now that we know its multifaceted clinical course, complications concerning the kidneys, and childhood-specific post-COVID pediatric inflammatory multisystem syndrome (PIMS), the value of diagnostic and prognostic biomarkers in the pediatric area should be appreciated, and their importance ought to increase

    Understanding the Sources, Atmospheric Evolution and Radiative Effect of Brown Carbon Aerosol Particles

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    Organic aerosols (OA) have long been thought to only scatter incoming solar radiation and have a cooling effect on climate. However, a fraction of OA, referred to as brown carbon (BrC), absorbs light in the lower visible to ultraviolet range. BrC can be emitted from incomplete combustions and can also be generated through secondary processes. The radiative impact of BrC on climate is difficult to assess owing to the lack of knowledge about emissions and the evolution of BrC aerosol. As part of the thesis work, the light absorption of BrC aerosol was measured with filters sampled from research aircraft during the NASA ATom mission. The aircraft flew from near surface to up to ~ 13 km altitude nearly pole to pole along the central Pacific and Atlantic Ocean basins and across the southern and Arctic Oceans, providing the first direct measurement of BrC aerosol on a global scale. BrC concentrations were found to be highly spatially heterogeneous, and high BrC levels were associated with the long-range transport of biomass burning emissions. A radiative transfer model suggested that BrC could substantially affect the global climate. The characteristics and evolution of BrC emitted from wildfires in the western US as part of the FIREX-AQ study were investigated. An optical closure analysis was performed to compare the overall light absorption measured by a photoacoustic spectrometer and the sum of the light absorption by individual light absorbers, including black carbon (BC) and BrC. The evolution of BrC was examined in the first few hours after emissions, but no consistent fate of BrC was observed. We found that BrC did not behave as the bulk OA or as a single BrC compound (4-Nitrocatechol) in response to change with temperature increases. Evidence was found that oxidation of ozone could cause BrC enhancement under high NOx conditions, while BrC could be bleached by ozone when NOx levels were low. Additionally, an online water-soluble BrC measuring system was developed and deployed in the FIREX-AQ. The newly built system was compared to two other systems with similar detection methods but different aerosol collection methods. In general, all three instruments can make effective BrC measurements in airborne campaigns, but baseline drift and signal hysteresis were observed. A possible approach to correct the baseline drift and hysteresis effect was proposed, along with possible methods for future improvements for these systems.Ph.D

    Poisson Brackets for some Coulomb Branches

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    We construct Poisson bracket relations between the operators which generate the chiral ring of the Coulomb branch of certain 3d3d N=4\mathcal{N}=4 quiver gauge theories. In the case where the Coulomb branch is a free space, ADEADE Klein singularity, or the minimal A2A_2 nilpotent orbit, we explicitly compute the Poisson brackets between the generators using either inherited properties of the abstract Coulomb branch variety, or the expected charges of these operators under the global symmetry (known through use of the monopole formula). We also conjecture Poisson brackets for Higgs branches that originate from 6d6d theories with tensionless strings or 5d5d theories with massless instantons for which the HWG is known, based on representation theoretic and operator content constraints known from the study of their magnetic quiver
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