2,435 research outputs found

    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

    Converging organoids and extracellular matrix::New insights into liver cancer biology

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    Converging organoids and extracellular matrix::New insights into liver cancer biology

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    Primary liver cancer, consisting primarily of hepatocellular carcinoma (HCC) and cholangiocarcinoma (CCA), is a heterogeneous malignancy with a dismal prognosis, resulting in the third leading cause of cancer mortality worldwide [1, 2]. It is characterized by unique histological features, late-stage diagnosis, a highly variable mutational landscape, and high levels of heterogeneity in biology and etiology [3-5]. Treatment options are limited, with surgical intervention the main curative option, although not available for the majority of patients which are diagnosed in an advanced stage. Major contributing factors to the complexity and limited treatment options are the interactions between primary tumor cells, non-neoplastic stromal and immune cells, and the extracellular matrix (ECM). ECM dysregulation plays a prominent role in multiple facets of liver cancer, including initiation and progression [6, 7]. HCC often develops in already damaged environments containing large areas of inflammation and fibrosis, while CCA is commonly characterized by significant desmoplasia, extensive formation of connective tissue surrounding the tumor [8, 9]. Thus, to gain a better understanding of liver cancer biology, sophisticated in vitro tumor models need to incorporate comprehensively the various aspects that together dictate liver cancer progression. Therefore, the aim of this thesis is to create in vitro liver cancer models through organoid technology approaches, allowing for novel insights into liver cancer biology and, in turn, providing potential avenues for therapeutic testing. To model primary epithelial liver cancer cells, organoid technology is employed in part I. To study and characterize the role of ECM in liver cancer, decellularization of tumor tissue, adjacent liver tissue, and distant metastatic organs (i.e. lung and lymph node) is described, characterized, and combined with organoid technology to create improved tissue engineered models for liver cancer in part II of this thesis. Chapter 1 provides a brief introduction into the concepts of liver cancer, cellular heterogeneity, decellularization and organoid technology. It also explains the rationale behind the work presented in this thesis. In-depth analysis of organoid technology and contrasting it to different in vitro cell culture systems employed for liver cancer modeling is done in chapter 2. Reliable establishment of liver cancer organoids is crucial for advancing translational applications of organoids, such as personalized medicine. Therefore, as described in chapter 3, a multi-center analysis was performed on establishment of liver cancer organoids. This revealed a global establishment efficiency rate of 28.2% (19.3% for hepatocellular carcinoma organoids (HCCO) and 36% for cholangiocarcinoma organoids (CCAO)). Additionally, potential solutions and future perspectives for increasing establishment are provided. Liver cancer organoids consist of solely primary epithelial tumor cells. To engineer an in vitro tumor model with the possibility of immunotherapy testing, CCAO were combined with immune cells in chapter 4. Co-culture of CCAO with peripheral blood mononuclear cells and/or allogenic T cells revealed an effective anti-tumor immune response, with distinct interpatient heterogeneity. These cytotoxic effects were mediated by cell-cell contact and release of soluble factors, albeit indirect killing through soluble factors was only observed in one organoid line. Thus, this model provided a first step towards developing immunotherapy for CCA on an individual patient level. Personalized medicine success is dependent on an organoids ability to recapitulate patient tissue faithfully. Therefore, in chapter 5 a novel organoid system was created in which branching morphogenesis was induced in cholangiocyte and CCA organoids. Branching cholangiocyte organoids self-organized into tubular structures, with high similarity to primary cholangiocytes, based on single-cell sequencing and functionality. Similarly, branching CCAO obtain a different morphology in vitro more similar to primary tumors. Moreover, these branching CCAO have a higher correlation to the transcriptomic profile of patient-paired tumor tissue and an increased drug resistance to gemcitabine and cisplatin, the standard chemotherapy regimen for CCA patients in the clinic. As discussed, CCAO represent the epithelial compartment of CCA. Proliferation, invasion, and metastasis of epithelial tumor cells is highly influenced by the interaction with their cellular and extracellular environment. The remodeling of various properties of the extracellular matrix (ECM), including stiffness, composition, alignment, and integrity, influences tumor progression. In chapter 6 the alterations of the ECM in solid tumors and the translational impact of our increased understanding of these alterations is discussed. The success of ECM-related cancer therapy development requires an intimate understanding of the malignancy-induced changes to the ECM. This principle was applied to liver cancer in chapter 7, whereby through a integrative molecular and mechanical approach the dysregulation of liver cancer ECM was characterized. An optimized agitation-based decellularization protocol was established for primary liver cancer (HCC and CCA) and paired adjacent tissue (HCC-ADJ and CCA-ADJ). Novel malignancy-related ECM protein signatures were found, which were previously overlooked in liver cancer transcriptomic data. Additionally, the mechanical characteristics were probed, which revealed divergent macro- and micro-scale mechanical properties and a higher alignment of collagen in CCA. This study provided a better understanding of ECM alterations during liver cancer as well as a potential scaffold for culture of organoids. This was applied to CCA in chapter 8 by combining decellularized CCA tumor ECM and tumor-free liver ECM with CCAO to study cell-matrix interactions. Culture of CCAO in tumor ECM resulted in a transcriptome closely resembling in vivo patient tumor tissue, and was accompanied by an increase in chemo resistance. In tumor-free liver ECM, devoid of desmoplasia, CCAO initiated a desmoplastic reaction through increased collagen production. If desmoplasia was already present, distinct ECM proteins were produced by the organoids. These were tumor-related proteins associated with poor patient survival. To extend this method of studying cell-matrix interactions to a metastatic setting, lung and lymph node tissue was decellularized and recellularized with CCAO in chapter 9, as these are common locations of metastasis in CCA. Decellularization resulted in removal of cells while preserving ECM structure and protein composition, linked to tissue-specific functioning hallmarks. Recellularization revealed that lung and lymph node ECM induced different gene expression profiles in the organoids, related to cancer stem cell phenotype, cell-ECM integrin binding, and epithelial-to-mesenchymal transition. Furthermore, the metabolic activity of CCAO in lung and lymph node was significantly influenced by the metastatic location, the original characteristics of the patient tumor, and the donor of the target organ. The previously described in vitro tumor models utilized decellularized scaffolds with native structure. Decellularized ECM can also be used for creation of tissue-specific hydrogels through digestion and gelation procedures. These hydrogels were created from both porcine and human livers in chapter 10. The liver ECM-based hydrogels were used to initiate and culture healthy cholangiocyte organoids, which maintained cholangiocyte marker expression, thus providing an alternative for initiation of organoids in BME. Building upon this, in chapter 11 human liver ECM-based extracts were used in combination with a one-step microfluidic encapsulation method to produce size standardized CCAO. The established system can facilitate the reduction of size variability conventionally seen in organoid culture by providing uniform scaffolding. Encapsulated CCAO retained their stem cell phenotype and were amendable to drug screening, showing the feasibility of scalable production of CCAO for throughput drug screening approaches. Lastly, Chapter 12 provides a global discussion and future outlook on tumor tissue engineering strategies for liver cancer, using organoid technology and decellularization. Combining multiple aspects of liver cancer, both cellular and extracellular, with tissue engineering strategies provides advanced tumor models that can delineate fundamental mechanistic insights as well as provide a platform for drug screening approaches.<br/

    Climate Change and Critical Agrarian Studies

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    Climate change is perhaps the greatest threat to humanity today and plays out as a cruel engine of myriad forms of injustice, violence and destruction. The effects of climate change from human-made emissions of greenhouse gases are devastating and accelerating; yet are uncertain and uneven both in terms of geography and socio-economic impacts. Emerging from the dynamics of capitalism since the industrial revolution — as well as industrialisation under state-led socialism — the consequences of climate change are especially profound for the countryside and its inhabitants. The book interrogates the narratives and strategies that frame climate change and examines the institutionalised responses in agrarian settings, highlighting what exclusions and inclusions result. It explores how different people — in relation to class and other co-constituted axes of social difference such as gender, race, ethnicity, age and occupation — are affected by climate change, as well as the climate adaptation and mitigation responses being implemented in rural areas. The book in turn explores how climate change – and the responses to it - affect processes of social differentiation, trajectories of accumulation and in turn agrarian politics. Finally, the book examines what strategies are required to confront climate change, and the underlying political-economic dynamics that cause it, reflecting on what this means for agrarian struggles across the world. The 26 chapters in this volume explore how the relationship between capitalism and climate change plays out in the rural world and, in particular, the way agrarian struggles connect with the huge challenge of climate change. Through a huge variety of case studies alongside more conceptual chapters, the book makes the often-missing connection between climate change and critical agrarian studies. The book argues that making the connection between climate and agrarian justice is crucial

    The role of heterosocial perception in men's likelihood to sexually harass

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    Sexual harassment against women represents sexually aggressive and coercive behaviour that violates women’s dignity and creates an offensive environment, which threatens women’s well-being and ability to prosper in day to day life (Pina, Gannon & Saunders, 2009). Understanding the perceptual characteristics of men with inclinations to sexually harass, through how they perceive women is important in delineating the reasons why some men may engage in the sexual harassment of women. Heterosocial perception is a concept of how an individual perceives another person interacting with the opposite sex. It is typically measured using the Test of Reading Affective Cues (TRAC), a tool encompassing an array of video clips showing a woman interacting with a man, whereby the woman displays a range of affective cues. The perceiver is assessed on their perceptual accuracy when judging the affective cues. Perceptual accuracies of male rapists and male child molesters have been well researched (Lipton, McDonel & McFall, 1987; Stahl & Sacco, 1995), yet male sexual harassment as a singular category has been neglected. The current thesis explores the potential heterosocial perception characteristics of a distinct group of men who are relatively high in the likelihood to engage in sexual harassment of women from scores on Pryor’s (1987) Likelihood to Sexually Harass (LSH) scale focusing on their differences in performance on the TRAC in comparison to those men who are lower in the likelihood to engage in sexual harassment of women. Five empirical studies are reported in this thesis. Study 1 presents a modernized version of the TRAC and incorporates an analysis to develop it as a research tool, enabling judgements on five affective cues displayed by a woman; friendly, romantic, neutral, bored and rejecting. The tool provides this range of affective cues that were used in later studies to measure differences in heterosocial perception. Study 2 addressed theoretical explanations taken from previous perception research with sexually aggressive men (Malamuth & Brown, xiv 1994) to explain differences in heterosocial perception for men high in LSH. Explanations are given for potential biases evidenced by men high in LSH focusing on Error Management Theory (Haselton & Buss, 2000) arguing that an overperception bias will increase the frequency of falsely inferring a woman’s sexual intent towards sexual pursuit, but considerably reduce the costs of losing a sexual opportunity by falsely inferring that a woman lacked sexual intent. Altogether, study 2 provided support for the misidentification of negative affective cues (negativeness blindness), the overperception of negative affective cues and the romantic overperception bias of friendly affective cues in the perception of men high in LSH. Study 3 tested the established theoretical link that internal concepts of social power have within men who report sexual aggression and sexual coercion and the subsequent impact on perception. Unexpectedly, power did not exacerbate perceptual inaccuracy for negative affective cues and the romantic overperception bias of friendly affective cues. In study 4, objectification was assessed in its relationship to perception in high LSH men. Instrumental and both specific and general sexual objectification were significantly higher for men high in LSH. Specific sexual objectification was found to negatively mediate romantic categorizations of romantic affective cues, but general sexual objectification was found to positively mediate romantic categorizations of friendly affective cues for men high in LSH. Results also showed that men high in LSH showed poorest perceptual accuracy on bored and rejecting affective cues, and evidenced a greater romantic judgement of friendly affective cues overperception bias. In study 5, the impact of different mental states on perception was assessed, via the use of a cooling system to facilitate self-regulation. A cooling system is a psychological framework proposed for understanding self-control (Metcalfe & Mischel, 1999), and in this study it incorporated techniques of distraction, distancing and empathy enhancement. Results showed that the cooling system was not beneficial in making high LSH xv men’s perceptual judgements more accurate and in making their judgements accurate to the level of low and medium LSH men for negative affective cues. However, cooling did improve perceptual accuracy of friendly affective cues removing the overperception bias to romantic judgements in comparison to the neutral condition. The cooling system was not found to reduce instrumental and sexual objectification for high LSH men. There were differences found on empathy between men high and low and medium on LSH. Differences were found such that men high in LSH showed more state empathy, but less trait empathy than men low and medium in LSH

    Effects of municipal smoke-free ordinances on secondhand smoke exposure in the Republic of Korea

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    ObjectiveTo reduce premature deaths due to secondhand smoke (SHS) exposure among non-smokers, the Republic of Korea (ROK) adopted changes to the National Health Promotion Act, which allowed local governments to enact municipal ordinances to strengthen their authority to designate smoke-free areas and levy penalty fines. In this study, we examined national trends in SHS exposure after the introduction of these municipal ordinances at the city level in 2010.MethodsWe used interrupted time series analysis to assess whether the trends of SHS exposure in the workplace and at home, and the primary cigarette smoking rate changed following the policy adjustment in the national legislation in ROK. Population-standardized data for selected variables were retrieved from a nationally representative survey dataset and used to study the policy action’s effectiveness.ResultsFollowing the change in the legislation, SHS exposure in the workplace reversed course from an increasing (18% per year) trend prior to the introduction of these smoke-free ordinances to a decreasing (−10% per year) trend after adoption and enforcement of these laws (β2 = 0.18, p-value = 0.07; β3 = −0.10, p-value = 0.02). SHS exposure at home (β2 = 0.10, p-value = 0.09; β3 = −0.03, p-value = 0.14) and the primary cigarette smoking rate (β2 = 0.03, p-value = 0.10; β3 = 0.008, p-value = 0.15) showed no significant changes in the sampled period. Although analyses stratified by sex showed that the allowance of municipal ordinances resulted in reduced SHS exposure in the workplace for both males and females, they did not affect the primary cigarette smoking rate as much, especially among females.ConclusionStrengthening the role of local governments by giving them the authority to enact and enforce penalties on SHS exposure violation helped ROK to reduce SHS exposure in the workplace. However, smoking behaviors and related activities seemed to shift to less restrictive areas such as on the streets and in apartment hallways, negating some of the effects due to these ordinances. Future studies should investigate how smoke-free policies beyond public places can further reduce the SHS exposure in ROK

    2023-2024 Catalog

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    The 2023-2024 Governors State University Undergraduate and Graduate Catalog is a comprehensive listing of current information regarding:Degree RequirementsCourse OfferingsUndergraduate and Graduate Rules and Regulation

    Child maintenance obligations in Malta: a qualitative study of fathers' perceptions and experiences

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    Child maintenance obligation is an important social policy issue given the benefits of child maintenance for children’s wellbeing as well as the role child maintenance plays in poverty reduction for payees and their children. This qualitative study sought to address the paucity of social science research on the issue in Malta – the home country of the author – by exploring the attitudes and behaviours of separated and divorced fathers in regard to child maintenance payment obligations. The study was underpinned by a critical realist relational perspective which incorporates a constructionist view of reality as being mediated by the interpretation of events experienced. Semi-structured interviews were held with 31 fathers who had undergone personal separation under Maltese law within the last 10 years. Transcripts were analysed using framework analysis which allowed for continuous comparison of themes for two groups of fathers, namely consenting and dissenting payers. Fathers’ stances towards child maintenance payment obligations were shown to be influenced by perceptions of un/fairness relating to three overarching themes: appraisal of the justice system; appraisal of financial contexts; and views on parenting. These findings provided support, to varying degrees, for four main theoretical frameworks: the theory of negotiated commitments; theory on the symbolic meanings of child maintenance monies; equity theory; and social negotiation theory. The concluding chapter reviews the study outcomes in the light of the aims, reflects on the limitations and originality of the thesis, and provides recommendations for future research. Fathers’ call for financial and parenting egalitarianism indicated a preference for new fatherhood ideals and for the re-evaluation of the role of financial provision, clashing with the gendered assumptions underpinning child maintenance obligations and raising important policy implications in regard to the complexity of challenges for policymakers to give primacy to both children and parents’ needs post-separation
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