4,604 research outputs found

    PAI-1 as a critical factor in the resolution of sepsis and acute kidney injury in old age

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    Elevated plasma levels of plasminogen activator inhibitor type 1 (PAI-1) are documented in patients with sepsis and levels positively correlate with disease severity and mortality. Our prior work demonstrated that PAI-1 in plasma is positively associated with acute kidney injury (AKI) in septic patients and mice. The objective of this study was to determine if PAI-1 is causally related to AKI and worse sepsis outcomes using a clinically-relevant and age-appropriate murine model of sepsis. Sepsis was induced by cecal slurry (CS)-injection to wild-type (WT, C57BL/6) and PAI-1 knockout (KO) mice at young (5–9 months) and old (18–22 months) age. Survival was monitored for at least 10 days or mice were euthanized for tissue collection at 24 or 48 h post-insult. Contrary to our expectation, PAI-1 KO mice at old age were significantly more sensitive to CS-induced sepsis compared to WT mice (24% vs. 65% survival, p = 0.0037). In comparison, loss of PAI-1 at young age had negligible effects on sepsis survival (86% vs. 88% survival, p = 0.8106) highlighting the importance of age as a biological variable. Injury to the kidney was the most apparent pathological consequence and occurred earlier in aged PAI-1 KO mice. Coagulation markers were unaffected by loss of PAI-1, suggesting thrombosis-independent mechanisms for PAI-1-mediated protection. In summary, although high PAI-1 levels are clinically associated with worse sepsis outcomes, loss of PAI-1 rendered mice more susceptible to kidney injury and death in a CS-induced model of sepsis using aged mice. These results implicate PAI-1 as a critical factor in the resolution of sepsis in old age

    TANDEM: taming failures in next-generation datacenters with emerging memory

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    The explosive growth of online services, leading to unforeseen scales, has made modern datacenters highly prone to failures. Taming these failures hinges on fast and correct recovery, minimizing service interruptions. Applications, owing to recovery, entail additional measures to maintain a recoverable state of data and computation logic during their failure-free execution. However, these precautionary measures have severe implications on performance, correctness, and programmability, making recovery incredibly challenging to realize in practice. Emerging memory, particularly non-volatile memory (NVM) and disaggregated memory (DM), offers a promising opportunity to achieve fast recovery with maximum performance. However, incorporating these technologies into datacenter architecture presents significant challenges; Their distinct architectural attributes, differing significantly from traditional memory devices, introduce new semantic challenges for implementing recovery, complicating correctness and programmability. Can emerging memory enable fast, performant, and correct recovery in the datacenter? This thesis aims to answer this question while addressing the associated challenges. When architecting datacenters with emerging memory, system architects face four key challenges: (1) how to guarantee correct semantics; (2) how to efficiently enforce correctness with optimal performance; (3) how to validate end-to-end correctness including recovery; and (4) how to preserve programmer productivity (Programmability). This thesis aims to address these challenges through the following approaches: (a) defining precise consistency models that formally specify correct end-to-end semantics in the presence of failures (consistency models also play a crucial role in programmability); (b) developing new low-level mechanisms to efficiently enforce the prescribed models given the capabilities of emerging memory; and (c) creating robust testing frameworks to validate end-to-end correctness and recovery. We start our exploration with non-volatile memory (NVM), which offers fast persistence capabilities directly accessible through the processor’s load-store (memory) interface. Notably, these capabilities can be leveraged to enable fast recovery for Log-Free Data Structures (LFDs) while maximizing performance. However, due to the complexity of modern cache hierarchies, data hardly persist in any specific order, jeop- ardizing recovery and correctness. Therefore, recovery needs primitives that explicitly control the order of updates to NVM (known as persistency models). We outline the precise specification of a novel persistency model – Release Persistency (RP) – that provides a consistency guarantee for LFDs on what remains in non-volatile memory upon failure. To efficiently enforce RP, we propose a novel microarchitecture mechanism, lazy release persistence (LRP). Using standard LFDs benchmarks, we show that LRP achieves fast recovery while incurring minimal overhead on performance. We continue our discussion with memory disaggregation which decouples memory from traditional monolithic servers, offering a promising pathway for achieving very high availability in replicated in-memory data stores. Achieving such availability hinges on transaction protocols that can efficiently handle recovery in this setting, where compute and memory are independent. However, there is a challenge: disaggregated memory (DM) fails to work with RPC-style protocols, mandating one-sided transaction protocols. Exacerbating the problem, one-sided transactions expose critical low-level ordering to architects, posing a threat to correctness. We present a highly available transaction protocol, Pandora, that is specifically designed to achieve fast recovery in disaggregated key-value stores (DKVSes). Pandora is the first one-sided transactional protocol that ensures correct, non-blocking, and fast recovery in DKVS. Our experimental implementation artifacts demonstrate that Pandora achieves fast recovery and high availability while causing minimal disruption to services. Finally, we introduce a novel target litmus-testing framework – DART – to validate the end-to-end correctness of transactional protocols with recovery. Using DART’s target testing capabilities, we have found several critical bugs in Pandora, highlighting the need for robust end-to-end testing methods in the design loop to iteratively fix correctness bugs. Crucially, DART is lightweight and black-box, thereby eliminating any intervention from the programmers

    Inklusive Bildung in Island: Grundlagen, Praktiken und Reflexionen

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    Der Sammelband bietet einen systematischen Überblick über Grundlagen, empirische Erkenntnisse und Reflexionen zur Umsetzung inklusiver Bildung im Bildungssystem Islands und regt so den internationalen Dialog an. Neben dem Fokus auf die gesellschaftliche Diskussion von Herausforderungen in Island im Vergleich zu deutschsprachigen Ländern werden von isländischen und deutschen Expert*innen Forschungs- und Qualifizierungsprojekte vorgestellt, Beispiele inklusiver Schulen und Lernprozesse erläutert sowie Erkenntnisse zur Gestaltung inklusionsorientierter Lehrer*innenbildung beschrieben

    Photoluminescent nano-CsPbBr3 embedded in Cs4PbBr6 crystals : formation mechanism and properties

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    WS would like to thank the China Scholarships Council and the University of St Andrews for the CSC-St Andrews studentship. Part of this work was financially supported by the National Science and Technology Council in Taiwan (Contract No. NSTC 112-2113-M-002-020) for RSL.Luminescent crystalline cesium lead bromide has been synthesized by using an antisolvent method with the nominal ratio of Cs:Pb in the precursors varying in a wide range from 4.5:1 to 1:1. Although the powder X-ray diffraction patterns of all the specimens show Cs4PbBr6 as a pure phase or a main phase, high-resolution transmission electron microscopy images reveal a large amount of CsPbBr3 nanocrystallites embedded in all the Cs4PbBr6 crystals. A formation mechanism of these perovskite nanocrystallites serving as actual active centers of photoluminescence is proposed. The most crucial step in the crystal growth is the deposition of a noncrystalline coating layer containing polymerized PbBr64– linked by Cs+ with the Cs:Pb ratio of about 3:1, and therefore, the actual crystal growth sites are at the interface between the crystal and the coating layer, instead of the crystal/solution interface. The local lack of Cs during the formation of Cs4PbBr6 results in the formation of CsPbBr3 nanocrystallites inside the parent crystals of Cs4PbBr6. The photoluminescence quantum yield and stability of the embedded CsPbBr3 nanocrystallites are significantly improved in comparison with bare CsPbBr3 crystals. Such simultaneous growth of parent crystals and the embedded nanocrystallites sheds light on further development of cesium lead halide-based photoluminescent materials.Publisher PDFPeer reviewe

    Impact evaluation midline report for FP026 - Sustainable Landscapes for Eastern Madagascar

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    The Sustainable Landscapes in Eastern Madagascar (SLEM) project (FP026) aims to increase the resilience of smallholder farmers and reduce carbon emissions by implementing climate-smart agriculture and more sustainable forest management in the remaining large blocks of forest in the eastern part of Madagascar covering 660,000 hectares across 15 districts. The estimation of the SLEM midline impacts relied on comparing the outputs and intermediate outcomes of early beneficiaries with those of beneficiaries who receive project interventions later. Baseline data was collected in early 2019 on 1,822 households from local community associations. These households were interviewed again for the midline survey in late 2022. A total of 1,654 were successfully re-interviewed, resulting in an attrition rate of 9.2 per cent. Midline results show significant improvements in households’ short-term outcomes, with widespread adoption of a range of conservation agriculture practices, such as soil conservation, agroforestry, terracing and drought-resistance crops. Households who have received the SLEM interventions report greater food security as measured by the Consolidated Approach for Reporting Indicators of Food Security index.They also report deriving less income from non-environmentally sustainable activities in both summer and winter. Overall, the promising outcomes observed in the midline results for short-term impacts suggest a trajectory towards achieving the SLEM’s medium-term and longer-term objectives. This assumption will be tested by measuring the project’s longer-term impacts in an endline survey planned for 202

    Significant spatial gradients in new particle formation frequency in Greece during summer

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    Extensive continuous particle number size distribution measurements took place during two summers (2020 and 2021) at 11 sites in Greece for the investigation of the frequency and the spatial extent of new particle formation (NPF). The study area is characterized by high solar intensity and fast photochemistry and has moderate to low fine particulate matter levels during the summer. The average PM2.5 levels were relatively uniform across the examined sites. The NPF frequency during summer varied from close to zero in the southwestern parts of Greece to more than 60 % in the northern, central, and eastern regions. The mean particle growth rate for each station varied between 3.4 and 8 nm h−1, with an average rate of 5.7 nm h−1. At most of the sites there was no statistical difference in the condensation sink between NPF event and non-event days, while lower relative humidity was observed during the events. The high-NPF-frequency sites in the north and northeast were in close proximity to both coal-fired power plants (high emissions of SO2) and agricultural areas with some of the highest ammonia emissions in the country. The southern and western parts of Greece, where NPF was infrequent, were characterized by low ammonia emissions, while moderate levels of sulfuric acid were estimated (107 molec. cm−3) in the west. Although the emissions of biogenic volatile organic compounds were higher in western and southern sectors, they did not appear to lead to enhanced frequency of NPF. The infrequent events at these sites occurred when the air masses had spent a few hours over areas with agricultural activities and thus elevated ammonia emissions. Air masses arriving at the sites directly from the sea were not connected with atmospheric NPF. These results support the hypothesis that ammonia and/or amines limit new particle formation in the study area.</p

    Heterogeneous machine learning ensembles for predicting train delays

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    Train delays have been a serious persisting problem in the UK and also many other countries. Due to increasing demand, rail networks are running close to their full capacity. As a consequence, an initial delay can cause many knock-on delays to other trains, and this is the main reason for the overall deterioration in the performance of the rail networks. Therefore, it is really useful to have an AI-based method that can predict delays accurately and reliably, to help train controllers to make and apply alternative plans in time to reduce or prevent further delays, when a delay occurs. However, existing machine learning models are not only inaccurate but more importantly unreliable. In this study, we have proposed a new approach to build heterogeneous ensembles with two novel model selection methods based on accuracy and diversity. We tested our heterogeneous ensembles using the real-world data and the results indicated that they are more accurate and robust than single models and state-of-the-art homogeneous ensembles, e.g. Random Forest and XGBoost. We then verified their performances with an independent dataset from a different train operating company and found that they achieved the consistent and accurate results

    Using theory of change to plan for the implementation of a psychological intervention addressing alcohol use disorder and psychological distress in Uganda.

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    In conflict-affected settings, prevalence of alcohol use disorders (AUDs) can be high. However, limited practical information exists on AUD management in low-income settings. Using a theory of change (ToC) approach, we aimed to identify pathways influencing the implementation and maintenance of a new transdiagnostic psychological intervention ("CHANGE"), targeting both psychological distress and AUDs in humanitarian settings. Three half-day workshops in Uganda engaged 41 stakeholders to develop a ToC map. ToC is a participatory program theory approach aiming to create a visual representation of how and why an intervention leads to specific outcomes. Additionally, five semi-structured interviews were conducted to explore experiences of stakeholders that participated in the ToC workshops. Two necessary pathways influencing the implementation and maintenance of CHANGE were identified: policy impact, and mental health service delivery. Barriers identified included policy gaps, limited recognition of social determinants and the need for integrated follow-up care. Interviewed participants valued ToC's participatory approach and expressed concerns about its adaptability in continuously changing contexts (e.g., humanitarian settings). Our study underscores ToC's value in delineating context-specific outcomes and identifies areas requiring further attention. It emphasizes the importance of early planning and stakeholder engagement for sustainable implementation of psychological interventions in humanitarian settings

    Engaging Girls in Computer Science: Do Single-Gender Interdisciplinary Classes Help?

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    Computing-driven innovation cannot reach its full potential if only a fraction of the population is involved. Without girls and their non-stereotypical contribution, the innovation potential is severely limited. In computer science (CS) and software engineering (SE), the gender gap persists without any positive trend. Many girls find it challenging to identify with the subject of CS. However, we can capitalize on their interests and create environments for girls through interdisciplinary subcultures to spark and foster enthusiasm for CS. This paper presents and discusses the results of an intervention in which we applied a novel interdisciplinary online course in data science to get girls excited about CS and programming by contributing to the grand goal of solving colony collapse disorder from biology and geoecology. The results show the potential of such programs to get girls excited about programming, but also important implications in terms of the learning environment. The startling results show that girls from single-gender classes (SGCs) are significantly more open to CS-related topics and that the intervention evoked significantly more positive feelings in them than in girls from mixed-gender classes (MGCs). The findings highlight the importance of how CS-related topics are introduced in school and the crucial impact of the learning environment to meet the requirements of truly gender-inclusive education
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