8,023 research outputs found

    Neuroanatomical and gene expression features of the rabbit accessory olfactory system. Implications of pheromone communication in reproductive behaviour and animal physiology

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    Mainly driven by the vomeronasal system (VNS), pheromone communication is involved in many species-specific fundamental innate socio-sexual behaviors such as mating and fighting, which are essential for animal reproduction and survival. Rabbits are a unique model for studying chemocommunication due to the discovery of the rabbit mammary pheromone, but paradoxically there has been a lack of knowledge regarding its VNS pathway. In this work, we aim at filling this gap by approaching the system from an integrative point of view, providing extensive anatomical and genomic data of the rabbit VNS, as well as pheromone-mediated reproductive and behavioural studies. Our results build strong foundation for further translational studies which aim at implementing the use of pheromones to improve animal production and welfare

    A Decision Support System for Economic Viability and Environmental Impact Assessment of Vertical Farms

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    Vertical farming (VF) is the practice of growing crops or animals using the vertical dimension via multi-tier racks or vertically inclined surfaces. In this thesis, I focus on the emerging industry of plant-specific VF. Vertical plant farming (VPF) is a promising and relatively novel practice that can be conducted in buildings with environmental control and artificial lighting. However, the nascent sector has experienced challenges in economic viability, standardisation, and environmental sustainability. Practitioners and academics call for a comprehensive financial analysis of VPF, but efforts are stifled by a lack of valid and available data. A review of economic estimation and horticultural software identifies a need for a decision support system (DSS) that facilitates risk-empowered business planning for vertical farmers. This thesis proposes an open-source DSS framework to evaluate business sustainability through financial risk and environmental impact assessments. Data from the literature, alongside lessons learned from industry practitioners, would be centralised in the proposed DSS using imprecise data techniques. These techniques have been applied in engineering but are seldom used in financial forecasting. This could benefit complex sectors which only have scarce data to predict business viability. To begin the execution of the DSS framework, VPF practitioners were interviewed using a mixed-methods approach. Learnings from over 19 shuttered and operational VPF projects provide insights into the barriers inhibiting scalability and identifying risks to form a risk taxonomy. Labour was the most commonly reported top challenge. Therefore, research was conducted to explore lean principles to improve productivity. A probabilistic model representing a spectrum of variables and their associated uncertainty was built according to the DSS framework to evaluate the financial risk for VF projects. This enabled flexible computation without precise production or financial data to improve economic estimation accuracy. The model assessed two VPF cases (one in the UK and another in Japan), demonstrating the first risk and uncertainty quantification of VPF business models in the literature. The results highlighted measures to improve economic viability and the viability of the UK and Japan case. The environmental impact assessment model was developed, allowing VPF operators to evaluate their carbon footprint compared to traditional agriculture using life-cycle assessment. I explore strategies for net-zero carbon production through sensitivity analysis. Renewable energies, especially solar, geothermal, and tidal power, show promise for reducing the carbon emissions of indoor VPF. Results show that renewably-powered VPF can reduce carbon emissions compared to field-based agriculture when considering the land-use change. The drivers for DSS adoption have been researched, showing a pathway of compliance and design thinking to overcome the ‘problem of implementation’ and enable commercialisation. Further work is suggested to standardise VF equipment, collect benchmarking data, and characterise risks. This work will reduce risk and uncertainty and accelerate the sector’s emergence

    In vitro investigation of the effect of disulfiram on hypoxia induced NFκB, epithelial to mesenchymal transition and cancer stem cells in glioblastoma cell lines

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    A thesis submitted in partial fulfilment of the requirements of the University of Wolverhampton for the degree of Doctor of Philosophy.Glioblastoma multiforme (GBM) is one of the most aggressive and lethal cancers with a poor prognosis. Advances in the treatment of GBM are limited due to several resistance mechanisms and limited drug delivery into the central nervous system (CNS) compartment by the blood-brain barrier (BBB) and by actions of the normal brain to counteract tumour-targeting medications. Hypoxia is common in malignant brain tumours such as GBM and plays a significant role in tumour pathobiology. It is widely accepted that hypoxia is a major driver of GBM malignancy. Although it has been confirmed that hypoxia induces GBM stem-like-cells (GSCs), which are highly invasive and resistant to all chemotherapeutic agents, the detailed molecular pathways linking hypoxia, GSC traits and chemoresistance remain obscure. Evidence shows that hypoxia induces cancer stem cell phenotypes via epithelial-to-mesenchymal transition (EMT), promoting therapeutic resistance in most cancers, including GBM. This study demonstrated that spheroid cultured GBM cells consist of a large population of hypoxic cells with CSC and EMT characteristics. GSCs are chemo-resistant and displayed increased levels of HIFs and NFκB activity. Similarly, the hypoxia cultured GBM cells manifested GSC traits, chemoresistance and invasiveness. These results suggest that hypoxia is responsible for GBM stemness, chemoresistance and invasiveness. GBM cells transfected with nuclear factor kappa B-p65 (NFκB-p65) subunit exhibited CSC and EMT markers indicating the essential role of NFκB in maintaining GSC phenotypes. The study also highlighted the significance of NFκB in driving chemoresistance, invasiveness, and the potential role of NFκB as the central regulator of hypoxia-induced stemness in GBM cells. GSC population has the ability of self-renewal, cancer initiation and development of secondary heterogeneous cancer. The very poor prognosis of GBM could largely be attributed to the existence of GSCs, which promote tumour propagation, maintenance, radio- and chemoresistance and local infiltration. In this study, we used Disulfiram (DS), a drug used for more than 65 years in alcoholism clinics, in combination with copper (Cu) to target the NFκB pathway, reverse chemoresistance and block invasion in GSCs. The obtained results showed that DS/Cu is highly cytotoxic to GBM cells and completely eradicated the resistant CSC population at low dose levels in vitro. DS/Cu inhibited the migration and invasion of hypoxia-induced CSC and EMT like GBM cells at low nanomolar concentrations. DS is an FDA approved drug with low toxicity to normal tissues and can pass through the BBB. Further research may lead to the quick translation of DS into cancer clinics and provide new therapeutic options to improve treatment outcomes in GBM patients

    Estudo da remodelagem reversa miocárdica através da análise proteómica do miocárdio e do líquido pericárdico

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    Valve replacement remains as the standard therapeutic option for aortic stenosis patients, aiming at abolishing pressure overload and triggering myocardial reverse remodeling. However, despite the instant hemodynamic benefit, not all patients show complete regression of myocardial hypertrophy, being at higher risk for adverse outcomes, such as heart failure. The current comprehension of the biological mechanisms underlying an incomplete reverse remodeling is far from complete. Furthermore, definitive prognostic tools and ancillary therapies to improve the outcome of the patients undergoing valve replacement are missing. To help abridge these gaps, a combined myocardial (phospho)proteomics and pericardial fluid proteomics approach was followed, taking advantage of human biopsies and pericardial fluid collected during surgery and whose origin anticipated a wealth of molecular information contained therein. From over 1800 and 750 proteins identified, respectively, in the myocardium and in the pericardial fluid of aortic stenosis patients, a total of 90 dysregulated proteins were detected. Gene annotation and pathway enrichment analyses, together with discriminant analysis, are compatible with a scenario of increased pro-hypertrophic gene expression and protein synthesis, defective ubiquitinproteasome system activity, proclivity to cell death (potentially fed by complement activity and other extrinsic factors, such as death receptor activators), acute-phase response, immune system activation and fibrosis. Specific validation of some targets through immunoblot techniques and correlation with clinical data pointed to complement C3 β chain, Muscle Ring Finger protein 1 (MuRF1) and the dual-specificity Tyr-phosphorylation regulated kinase 1A (DYRK1A) as potential markers of an incomplete response. In addition, kinase prediction from phosphoproteome data suggests that the modulation of casein kinase 2, the family of IκB kinases, glycogen synthase kinase 3 and DYRK1A may help improve the outcome of patients undergoing valve replacement. Particularly, functional studies with DYRK1A+/- cardiomyocytes show that this kinase may be an important target to treat cardiac dysfunction, provided that mutant cells presented a different response to stretch and reduced ability to develop force (active tension). This study opens many avenues in post-aortic valve replacement reverse remodeling research. In the future, gain-of-function and/or loss-of-function studies with isolated cardiomyocytes or with animal models of aortic bandingdebanding will help disclose the efficacy of targeting the surrogate therapeutic targets. Besides, clinical studies in larger cohorts will bring definitive proof of complement C3, MuRF1 and DYRK1A prognostic value.A substituição da válvula aórtica continua a ser a opção terapêutica de referência para doentes com estenose aórtica e visa a eliminação da sobrecarga de pressão, desencadeando a remodelagem reversa miocárdica. Contudo, apesar do benefício hemodinâmico imediato, nem todos os pacientes apresentam regressão completa da hipertrofia do miocárdio, ficando com maior risco de eventos adversos, como a insuficiência cardíaca. Atualmente, os mecanismos biológicos subjacentes a uma remodelagem reversa incompleta ainda não são claros. Além disso, não dispomos de ferramentas de prognóstico definitivos nem de terapias auxiliares para melhorar a condição dos pacientes indicados para substituição da válvula. Para ajudar a resolver estas lacunas, uma abordagem combinada de (fosfo)proteómica e proteómica para a caracterização, respetivamente, do miocárdio e do líquido pericárdico foi seguida, tomando partido de biópsias e líquidos pericárdicos recolhidos em ambiente cirúrgico. Das mais de 1800 e 750 proteínas identificadas, respetivamente, no miocárdio e no líquido pericárdico dos pacientes com estenose aórtica, um total de 90 proteínas desreguladas foram detetadas. As análises de anotação de genes, de enriquecimento de vias celulares e discriminativa corroboram um cenário de aumento da expressão de genes pro-hipertróficos e de síntese proteica, um sistema ubiquitina-proteassoma ineficiente, uma tendência para morte celular (potencialmente acelerada pela atividade do complemento e por outros fatores extrínsecos que ativam death receptors), com ativação da resposta de fase aguda e do sistema imune, assim como da fibrose. A validação de alguns alvos específicos através de immunoblot e correlação com dados clínicos apontou para a cadeia β do complemento C3, a Muscle Ring Finger protein 1 (MuRF1) e a dual-specificity Tyr-phosphoylation regulated kinase 1A (DYRK1A) como potenciais marcadores de uma resposta incompleta. Por outro lado, a predição de cinases a partir do fosfoproteoma, sugere que a modulação da caseína cinase 2, a família de cinases do IκB, a glicogénio sintase cinase 3 e da DYRK1A pode ajudar a melhorar a condição dos pacientes indicados para intervenção. Em particular, a avaliação funcional de cardiomiócitos DYRK1A+/- mostraram que esta cinase pode ser um alvo importante para tratar a disfunção cardíaca, uma vez que os miócitos mutantes responderam de forma diferente ao estiramento e mostraram uma menor capacidade para desenvolver força (tensão ativa). Este estudo levanta várias hipóteses na investigação da remodelagem reversa. No futuro, estudos de ganho e/ou perda de função realizados em cardiomiócitos isolados ou em modelos animais de banding-debanding da aorta ajudarão a testar a eficácia de modular os potenciais alvos terapêuticos encontrados. Além disso, estudos clínicos em coortes de maior dimensão trarão conclusões definitivas quanto ao valor de prognóstico do complemento C3, MuRF1 e DYRK1A.Programa Doutoral em Biomedicin

    The Future of Work and Digital Skills

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    The theme for the events was "The Future of Work and Digital Skills". The 4IR caused a hollowing out of middle-income jobs (Frey & Osborne, 2017) but COVID-19 exposed the digital gap as survival depended mainly on digital infrastructure and connectivity. Almost overnight, organizations that had not invested in a digital strategy suddenly realized the need for such a strategy and the associated digital skills. The effects have been profound for those who struggled to adapt, while those who stepped up have reaped quite the reward.Therefore, there are no longer certainties about what the world will look like in a few years from now. However, there are certain ways to anticipate the changes that are occurring and plan on how to continually adapt to an increasingly changing world. Certain jobs will soon be lost and will not come back; other new jobs will however be created. Using data science and other predictive sciences, it is possible to anticipate, to the extent possible, the rate at which certain jobs will be replaced and new jobs created in different industries. Accordingly, the collocated events sought to bring together government, international organizations, academia, industry, organized labour and civil society to deliberate on how these changes are occurring in South Africa, how fast they are occurring and what needs to change in order to prepare society for the changes.Deutsche Gesellschaft für Internationale Zusammenarbeit (GIZ) British High Commission (BHC)School of Computin

    Omics measures of ageing and disease susceptibility

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    While genomics has been a major field of study for decades due to relatively inexpensive genotyping arrays, the recent advancement of technology has also allowed the measure and study of various “omics”. There are now numerous methods and platforms available that allow high throughput and high dimensional quantification of many types of biological molecules. Traditional genomics and transcriptomics are now joined by proteomics, metabolomics, glycomics, lipidomics and epigenomics. I was lucky to have access to a unique resource in the Orkney Complex Disease Study (ORCADES), a cohort of individuals from the Orkney Islands that are extremely deeply annotated. Approximately 1000 individuals in ORCADES have genomics, proteomics, lipidomics, glycomics, metabolomics, epigenomics, clinical risk factors and disease phenotypes, as well as body composition measurements from whole body scans. In addition to these cross-sectional omics and health related measures, these individuals also have linked electronic health records (EHR) available, allowing the assessment of the effect of these omics measures on incident disease over a ~10-year follow up period. In this thesis I use this phenotype rich resource to investigate the relationship between multiple types of omics measures and both ageing and health outcomes. First, I used the ORCADES data to construct measures of biological age (BA). The idea that there is an underlying rate at which the body deteriorates with age that varies between individuals of the same chronological age, this biological age, would be more indicative of health status, functional capacity and risk of age-related diseases than chronological age. Previous models estimating BA (ageing clocks) have predominantly been built using a single type of omics assay and comparison between different omics ageing clocks has been limited. I performed the most exhaustive comparison of different omics ageing clocks yet, with eleven clocks spanning nine different omics assays. I show that different omics clocks overlap in the information they provide about age, that some omics clocks track more generalised ageing while others track specific disease risk factors and that omics ageing clocks are prognostic of incident disease over and above chronological age. Second, I assessed whether individually or in multivariable models, omics measures are associated with health-related risk factors or prognostic of incident disease over 10 years post-assessment. I show that 2,686 single omics biomarkers are associated with 10 risk factors and 44 subsequent incident diseases. I also show that models built using multiple biomarkers from whole body scans, metabolomics, proteomics and clinical risk factors are prognostic of subsequent diabetes mellitus and that clinical risk factors are prognostic of incident hypertensive disorders, obesity, ischaemic heart disease and Framingham risk score. Third, I investigated the genetic architecture of a subset of the proteomics measures available in ORCADES, specifically 184 cardiovascular-related proteins. Combining genome-wide association (GWAS) summary statistics from ORCADES and 17 other cohorts from the SCALLOP Consortium, giving a maximum sample size of 26,494 individuals, I performed 184 genome-wide association meta-analyses (GWAMAs) on the levels of these proteins circulating in plasma. I discovered 592 independent significant loci associated with the levels of at least one protein. I found that between 8-37% of these significant loci colocalise with known expression quantitative trait loci (eQTL). I also find evidence of causal associations between 11 plasma protein levels and disease susceptibility using Mendelian randomisation, highlighting potential candidate drug targets

    Full stack development toward a trapped ion logical qubit

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    Quantum error correction is a key step toward the construction of a large-scale quantum computer, by preventing small infidelities in quantum gates from accumulating over the course of an algorithm. Detecting and correcting errors is achieved by using multiple physical qubits to form a smaller number of robust logical qubits. The physical implementation of a logical qubit requires multiple qubits, on which high fidelity gates can be performed. The project aims to realize a logical qubit based on ions confined on a microfabricated surface trap. Each physical qubit will be a microwave dressed state qubit based on 171Yb+ ions. Gates are intended to be realized through RF and microwave radiation in combination with magnetic field gradients. The project vertically integrates software down to hardware compilation layers in order to deliver, in the near future, a fully functional small device demonstrator. This thesis presents novel results on multiple layers of a full stack quantum computer model. On the hardware level a robust quantum gate is studied and ion displacement over the X-junction geometry is demonstrated. The experimental organization is optimized through automation and compressed waveform data transmission. A new quantum assembly language purely dedicated to trapped ion quantum computers is introduced. The demonstrator is aimed at testing implementation of quantum error correction codes while preparing for larger scale iterations.Open Acces

    Examination of a Brief, Self-Paced Online Self-Compassion Intervention Targeting Intuitive Eating and Body Image Outcomes among Men and Women

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    Ideals for appearance and body image are pervasive in Western culture in which men and women are portrayed with unrealistic and often unattainable standards (Ferguson, 2013; Martin, 2010). Exposure and reinforcement have created a culture of social acceptance and internalization of these ideals, contributing to pervasive body image disturbance (i.e., body dissatisfaction; Fallon et al., 2014; Stice, 2001; Thompson & Stice, 2001; Thompson et al., 1999). Research has suggested that body dissatisfaction is expressed differently across sexes (Grossbard et al., 2008), with attention to thin ideals among women and muscular ideals among men. Body dissatisfaction has been linked to numerous poor outcomes, including dieting, unhealthy weight control behaviors, disordered eating, and increased psychopathology. Although dieting is one of the primary mechanisms employed to reduce body dissatisfaction (Thompson & Stice, 2001), research has shown that such efforts are contraindicated as dieting predicts weight gain over time (Pietiläinen et al., 2012) as well as preoccupation with food, disordered eating, eating disorders, emotional distress, and higher body dissatisfaction (Grabe et al., 2007; Johnson & Wardle, 2005; Neumark- Sztianer et al., 2006; Paxton et al., 2006; Tiggemann, 2005). Restrictive dietary behaviors suppress physiological cues to eat (e.g., hunger) that presents a vulnerability to eating in response to alternative cues, both internal (e.g., emotions) and external (e.g., availability of food). Intuitive eating is a non-restrictive approach to eating that encourages adherence to internal physiological cues to indicate when, what, and how much to eat (Tylka, 2006) and has demonstrated an inverse relationship with disordered eating, restrained eating, food preoccupation, dieting, body dissatisfaction, and negative affect (Bruce & Ricciardelli, 2016). Self-compassion, relating to oneself in a caring and supportive manner (Neff, 2003a), has been proposed as a pathway to increase intuitive eating and reduce body dissatisfaction (Neff & Knox, 2017; Schoenefeld & Webb, 2013; Webb & Hardin, 2016). Research has highlighted the efficacy of self-compassion interventions in addressing weight-related concerns (Rahimi-Ardabili et al., 2018) as well as brief experiential exercises for reducing body dissatisfaction (Moffitt et al., 2018). Additionally, there is a growing body of evidence supporting the efficacy of internet-based self-compassion interventions (Mak et al., 2018; Kelman et al., 2018; Nadeau et al., 2020). The purpose of the current study was to examine the effectiveness of a brief, self-paced online self-compassion intervention targeting body image and adaptive eating behaviors and potential mechanisms of change (e.g., self-compassion and psychological flexibility) among undergraduate men and women. This study also examined outcomes among men and women in the area of self-compassion, body dissatisfaction, and intuitive eating as research has highlighted the need to determine who benefits more from self-compassion interventions (Rahimi-Ardabili et al., 2018). The study compared a one-hour, self-guided online self-compassion intervention to an active control condition. The intervention was comprised of psychoeducation, experiential exercises, and mindfulness practice designed to increase self-compassion surrounding body image and eating behaviors. In contrast, the active control condition consisted of self-care recommendations and self-assessments for nutrition, exercise, and sleep. The study was administered over three parts (e.g., baseline, intervention, and follow-up) in which variables of interest were assessed at each time point. Outcome variables included self-compassion, intuitive eating, disordered eating, body appreciation, muscle dysmorphia, internalized weight bias, fear of self-compassion, and psychological inflexibility. Participants were randomized on a 2:1 intervention to control ratio at the second time point in order to make comparisons between groups while simultaneously having sufficient power for examining mediation and moderation within the treatment condition. Overall, 1023 individuals (64% women, Mage = 18.9, 67.4% white) signed informed consent and participated in at least one part of the study whereas 101 participants (71% women, Mage = 19.3, 71% white) completed all three study portions. As predicted, self-compassion was correlated with all variables of interest, and all study variables were correlated with each other (p < .01). In contrast to hypothesized outcomes, the self-compassion condition failed to demonstrate improvements across time or between conditions on all study outcomes. These results persisted when participants were screened for levels of intuitive eating as well. Contrary to prediction, internalized weight bias, muscle dysmorphia, and fear of self-compassion demonstrated increased levels within the intervention condition and decreases in the control condition. There were significant gender differences on multiple outcome variables, with men demonstrating higher levels of self-compassion and body appreciation whereas women endorsed higher levels of disordered eating, internalized weight bias, muscle dysmorphia, and psychological inflexibility. Additionally, there were significant gender interactions for internalized weight bias, body appreciation, and muscle dysmorphia. The interactions existed such that men demonstrated increased internalized weight bias and muscle dysmorphia across time whereas women displayed decreased weight bias and muscle dysmorphia. The opposite pattern was found within body appreciation; women demonstrated increased body appreciation across time while men reported decreased levels of body appreciation. Despite this study’s intent to examine underlying mechanisms of change, the condition in which participants were randomly selected did not have any relationship, positive or negative, with the outcome variables of interest. As such, mediation within the current study was not conducted as it would violate statistical assumptions required to examine this hypothesis. Finally, upon examining the moderating relationship of fear of self-compassion between self-compassion and outcome variables, there were main effects for self-compassion on intuitive eating, emotional eating, internalized weight bias, body appreciation, and psychological inflexibility as well as main effects of fear of self-compassion on psychological inflexibility. There were significant interactions for intuitive eating and emotional eating, such that as fear of self-compassion increased, the effect of self-compassion on intuitive eating decreased, and the effect of self-compassion on reducing emotional eating behaviors decreased. Overall, the brief, self-paced online intervention delivered in the current study did not prove to be an effective means for improving self-compassion, intuitive eating, body appreciation, disordered eating, muscle dysmorphia, and psychological inflexibility. Nevertheless, the relationships between self-compassion and outcome variables of interest throughout the study mirror that of the existing literature. Findings from this study, in general, were also consistent with differences between men and women despite a gap in the research for intervention outcomes. Although fear of self-compassion demonstrated a moderating effect on the relationship between self-compassion and intuitive eating as well as emotional eating, this does not account for the lack of significant findings. The context surrounding this study, such as the COVID-19 pandemic, provided a considerable challenge to examining the efficacy of the current intervention. However, the findings of this study suggest future research will likely need to identify ways to enhance the delivery of experiential exercises that encourage engagement, provide a safe and warm environment for participants, and create flexibility and willingness surrounding painful and difficult experiences in order to undermine internalized and socially accepted beliefs about body image and eating behaviors

    AIUCD 2022 - Proceedings

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    L’undicesima edizione del Convegno Nazionale dell’AIUCD-Associazione di Informatica Umanistica ha per titolo Culture digitali. Intersezioni: filosofia, arti, media. Nel titolo è presente, in maniera esplicita, la richiesta di una riflessione, metodologica e teorica, sull’interrelazione tra tecnologie digitali, scienze dell’informazione, discipline filosofiche, mondo delle arti e cultural studies

    SYSTEMS METHODS FOR ANALYSIS OF HETEROGENEOUS GLIOBLASTOMA DATASETS TOWARDS ELUCIDATION OF INTER-TUMOURAL RESISTANCE PATHWAYS AND NEW THERAPEUTIC TARGETS

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    In this PhD thesis is described an endeavour to compile litterature about Glioblastoma key molecular mechanisms into a directed network followin Disease Maps standards, analyse its topology and compare results with quantitative analysis of multi-omics datasets in order to investigate Glioblastoma resistance mechanisms. The work also integrated implementation of Data Management good practices and procedures
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