179566 research outputs found
Sort by
An efficient active-set method with applications to sparse approximations and risk minimization
No full textIn this paper we present an efficient active-set method for the solution of convex quadratic programming problems with general piecewise-linear terms in the objective, with applications to sparse approximations and risk-minimization. The algorithm is derived by combining a proximal method of multipliers (PMM) with a standard semismooth Newton method (SSN), and is shown to be globally convergent under minimal assumptions. Further local linear (and potentially superlinear) convergence is shown under standard additional conditions. The major computational bottleneck of the proposed approach arises from the solution of the associated SSN linear systems. These are solved using a Krylov-subspace method, accelerated by certain novel general-purpose preconditioners which are shown to be optimal with respect to the proximal penalty parameters. The preconditioners are easy to store and invert, since they exploit the structure of the nonsmooth terms appearing in the problem’s objective to significantly reduce their memory requirements. We showcase the efficiency, robustness, and scalability of the proposed solver on a variety of problems arising in risk-averse portfolio selection, L1-regularized partial differential equation constrained optimization, quantile regression, and binary classification via linear support vector machines. We provide computational evidence, on real-world datasets, to demonstrate the ability of the solver to efficiently and competitively handle a diverse set of medium- and large-scale optimization instances.</p
Bystander activation across a TAD boundary supports a cohesin-dependent transcription cluster model for enhancer function
No full textMammalian enhancers can regulate genes over large genomic distances, often skipping over other genes. Despite this, precise developmental regulation suggests that mechanisms exist to ensure enhancers only activate their correct targets. Sculpting of three-dimensional chromosome organization through cohesin-dependent loop extrusion is thought to be important for facilitating and constraining enhancer action. The boundaries of topologically associating domains (TADs) are thought to prevent enhancers acting on genes in adjacent TADs. However, there are examples where enhancers appear to act across TAD boundaries, but it has remained unclear whether a single enhancer can simultaneously activate genes in different TADs. Here we show that some Shh enhancers can activate transcription concurrently not only at Shh but also at Mnx1 located in an adjacent TAD. This occurs in the context of a chromatin conformation maintaining genes and enhancers in close proximity and is influenced by cohesin. To our knowledge, this is the first report of two endogenous mammalian genes transcribed concurrently under the control of the same enhancer and across a TAD boundary. These findings have implications for understanding the design rules of gene regulatory landscapes and are consistent with a transcription cluster model of enhancer-promoter communication
Halloysite nanotubes potentiate protein assembly for facile fabrication of nanocomposite thin film and its application in wound dressing
No full textProtein films offer a promising alternative to traditional synthetic polymer materials because of their nontoxicity, biocompatibility and biodegradability, particularly in the biomedical field. However, their practical use has remained a challenge due to their low mechanical strength, poor aqueous stability and high production costs. In this work, we prepared an organic-inorganic protein-based composite film by incorporating vancomycin-loaded halloysite nanotubes (Hal) and bovine serum albumin (BSA) with a facile and biocompatible method. In the composite film, the abundant α-helix structure in BSA was reduced and transformed into a β-sheet-rich phase-transition BSA (PTB), which then interacted with vancomycin-loaded Hal (VHal) through hydrogen bonding to form a cross-linked network structure. Hal can not only reinforce the protein self-assembly via noncovalent interactions to improve the mechanical strength and stability of the protein film, but also act as carriers of antibacterial agents for a sustained drug release system. As a result, the resultant VHal/PTB composite film could completely eliminate Staphylococcus aureus within 30 min and demonstrated excellent biocompatibility. In vivo studies further showed that the composite film could effectively inhibit bacterial infections and accelerate the healing of infected skin wounds in mouse skin, with near-complete wound closure achieved within 12 days. The design strategy of this robust, breathable and biocompatible nanocomposite protein film with antibacterial properties sheds new light on the development of multifunctional wound dressings for infected wound tissue.</p
Transcriptomic characterization of transitioning cell types in the skin of Atlantic salmon
No full textBACKGROUND: The skin maintains the body's integrity and serves as the first line of defence against pathogens, stressors and mechanical injuries. Despite the global significance of salmon in aquaculture, how the transcriptomic profile of cells varies during wound healing remains unexplored. Teleost's skin contains adult pluripotent cells that differentiate into various tissues, including bone, cartilage, tendon, ligament, adipose, dermis, muscle and connective tissue within the skin. These cells are pivotal for preserving the integrity of skin tissue throughout an organism's lifespan and actively participate in the wound healing processes. In this study, we characterize the transcriptomic profiles of putative mesenchymal stromal cells (fibroblast-like adult stem cells) in healthy Atlantic salmon tissue and during the wound healing process.RESULTS: Single-nucleus sequencing and spatial transcriptomics were used to detect transcriptomic changes occurring during wound healing that are commonly associated with mesenchymal stromal cells. We followed the transcriptomic activity of these cells during an in vivo wound healing time course study showing that these cells become more transcriptionally active during the remodelling stage of wound healing. The changes detected give insights into the potential differentiation pathways leading to osteogenic and fibroblast lineages in the skin of Atlantic salmon.CONCLUSIONS: We chart the transcriptomic activity of subclusters of putative differentiating stromal cells during the process of wound healing for the first time, revealing different spatial niches of the various putative MSC subclusters, and setting the stage for further investigation of the manipulation of transitioning cell types to improve fish health.</p
Consensus classification of biliary complications after liver transplantation:guidelines from the BileducTx meeting
No full textPress freedom and stock price crash risk
No full textThis paper examines the impact of press freedom, an important institutional factor, on stock price crash risk. Using a large international sample of firms across 52 economies between 2002 and 2021, we find that firms in economies with higher degrees of press freedom are associated with lower levels of future stock price crash risk. Our analysis further shows that press freedom helps to deter the hoarding of bad news by increasing the intensity of reporting, extending the reporting period, and broadening local media coverage. Firms operating in economies with press freedom demonstrate stronger corporate governance and lower levels of firm-specific and long-term overvaluation, which are likely mechanisms through which press freedom mitigates crash risk. The negative impact of press freedom on crash risk is weakened by corruption but strengthened for firms facing higher short interest and less analyst coverage. Additional tests reveal that this negative relationship is driven by a collective influence from multiple dimensions of press freedom. Our results survive a battery of robustness checks. In sum, our findings suggest that press freedom enhances the stability of the global stock market by discouraging the concealment of negative information
CVD grown SnS2 Active Layers on AlGaN/GaN HEMT for Arsenic (III) Ions Detection
No full textThe pervasive contamination of water sources by the toxic heavy metal arsenic presents a serious threat to human health and ecological systems. This raises the critical need for innovative detection platforms that can detect such contamination at low cost and as part of an onsite, distributed sensor network. In this context, we report an Arsenic (As 3+) ion detection system that was fabricated using 2D SnS 2 functionalized AlGaN/GaN high electron mobility transistor (HEMT). SnS 2 layers were grown on the HEMT surface by chemical vapor deposition (CVD) which depicts hexagonal oriented nanosheets with crystal edges. The source and drain tri-metal contacts of Au/Cr/Al were fabricated by thermal evaporation using shadow mask. The sensor response was analyzed by measuring the variation in drain to source current of the device after introducing varied concentrations of As 3+ ions, ranging from 1 ppb to 10 ppm. The observed sensitivity of the device is 0.42 μA ppb −1, with a detection limit of 0.90 ppb, and a response time of 3.2 s. Further, real-time data analysis was performed by the integration of the developed sensor with a customized printed circuit board connected with an Arduino Nano 33 Bluetooth Low Energy (BLE) module for data transmission. The concept of growing the SnS 2 layer as a functionalizing layer by CVD results in quick response, good repeatability, and selectivity thereby eliminating the need for any additional reference electrode. Integration of the developed AlGaN/GaN HEMT sensor with Arduino Nano 33 BLE makes it an ideal candidate for portable heavy metal ion sensing device for onsite detection.</p
Psychological and emotional harms of online child sexual exploitation and abuse in children under the age of 18:A systematic review of the evidence
No full textOnline child sexual exploitation and abuse (OCSEA) is a growing public health concern, with significant psychological and emotional impacts on victims. As digital communication evolves, the complexity and prevalence of OCSEA increase, highlighting the need for a comprehensive understanding of its effects on children. This systematic review examines the psychological and emotional harms experienced by victims under 18, with the goal of improving prevention and intervention strategies. This review also explores the relationship between specific forms of OCSEA and their psychological outcomes, informing future policies and practices. Following Cochrane guidelines and PRISMA standards, this review covers studies from 1989 onwards, including primary, secondary and mixed-methods research, as well as grey literature. Studies reporting psychological or emotional harm due to OCSEA victimisation are included. Data extraction and quality assessment were performed using standardised tools, and a narrative synthesis was employed to summarise the findings. This review enhances understanding of the psychological and emotional impacts of OCSEA, supporting the development of effective strategies for prevention and intervention.</p
“Sport is NOT a luxury.” The perceived impact of the cost-of-living crisis on sport and physical activity opportunities for children and adolescents in Northern Ireland (NI):A cross-sectional survey
No full textBackground: Worldwide, it is of public health concern that the majority of children and adolescents fail to meet physical activity guidelines. Evidence shows a positive association between socioeconomic status (SES) and levels of physical activity. Socioeconomic health inequalities are persistent and the socioeconomic gap in physical activity may be exacerbated during periods of economic downturn such as the current cost-of-living crisis affecting many countries globally. This study aimed to understand the perceived impact of the cost-of-living crisis on access to sport and physical activity opportunities for children and adolescents. Methods: Parents/guardians (aged > 18 years) resident in Northern Ireland (NI) were invited to participate in an online survey (March–June 2024) which assessed SES, parental support for physical activity and the perceived impact of the cost-of-living crisis on access to sport and physical activity opportunities for children and adolescents. Thematic (qualitative data) and statistical analysis (quantitative data) was undertaken. Results: In total, 855 parents/guardians completed the survey. The majority of parents/guardians (85%) agreed that sport and physical activity were important for their children to manage stress, however, 30% were unable to afford the equipment and clothing that their children needed to participate in sport/physical activity. More than a third of parents/guardians (35%) had reduced spending on sport and physical activity for their children since the onset of the cost-of-living crisis. For 37% of parents/guardians, their children had missed out on sport/physical activity because of the costs involved and 24% of parents/guardians reported using credit or borrowing money to cover sport and physical activity costs. The perceived impact of the cost-of-living crisis on sport and physical activity opportunities for children varied by SES. A greater proportion of parents/guardians with lower SES reported reducing spending and borrowing money to cover sport/physical activity related costs. Conclusions: Despite parental support for children’s sport and physical activity, cost was a barrier for many families. The ‘socioeconomic gap’ in physical activity and sports provision was evident and although establishing positive physical activity and sedentary behaviours during childhood is crucial, the cost-of-living crisis is likely to worsen the existing SES gap in physical activity and requires urgent intervention. Trial registration: N/A.</p
Justice by Design:Integrating energy justice and responsible research and innovation (RRI) to deliver just energy futures
Get PDFThe deployment of low-carbon energy systems will have a variety of social and environmental impacts. Notwithstanding this, current just transitions work continues to focus on the mitigation of harm following fossil fuel industry closures, largely neglecting the potential impacts of future energy developments. While energy justice scholarship scrutinises low-carbon energy sources, it remains largely focused on the mitigation of injustice retrospectively, whereas explorations of future energy types and their potential justice implications are lacking. To address this gap, this paper presents ‘Justice by Design’: an interdisciplinary conceptual framework and practical methodology. Justice by Design integrates energy justice with responsible research and innovation to better anticipate justice in future energy systems, with a view to actively designing and hence delivering just (energy) transitions. We propose that Justice by Design can be used methodologically to scrutinise energy sources, energy technologies, energy projects and place-specific energy system changes. The paper begins by providing critical overviews of just transitions, energy justice and responsible research and innovation literatures. We then present the Justice by Design conceptual framework and methodology, alongside guidance for its implementation. This is followed by discussion on its applicability and limitations. Justice by Design can support the proactive identification of injustice risks while prompting practitioners to seek out justice-building opportunities – setting out an anticipatory justice approach throughout energy system redesign.</p
Access Repository Dashboard
Do you manage Edinburgh Research Explorer? Access insider analytics, issue reports and manage access to outputs from your repository in the CORE Repository Dashboard!