174 research outputs found
Sustainable Phosphorus Loadings from Effective and Cost-Effective Phosphorus Management Around the Baltic Sea
Nutrient over-enrichment of the Baltic Sea, accompanied by intensified algal blooms and decreasing water clarity, has aroused widespread concern in the surrounding countries during the last four decades. This work has used a well-tested dynamic mass-balance model to investigate which decrease in total phosphorus loading would be required to meet the environmental goal to restore the trophic state in the Baltic Sea to pre-1960s levels. Furthermore, the extent to which various abatement options may decrease the phosphorus loading in a cost-effective manner has been studied. Upgrading urban sewage treatment in the catchment could, alone or in combination with banning phosphates in detergents, be sufficient to meet the set environmental goal, at an estimated annual basin-wide cost of 0.21–0.43 billion euro. Such a plan would potentially decrease the total phosphorus loading to the Baltic Sea with 6,650–10,200 tonnes per year
Molecular crowding defines a common origin for the Warburg effect in proliferating cells and the lactate threshold in muscle physiology
Aerobic glycolysis is a seemingly wasteful mode of ATP production that is seen both in rapidly proliferating mammalian cells and highly active contracting muscles, but whether there is a common origin for its presence in these widely different systems is unknown. To study this issue, here we develop a model of human central metabolism that incorporates a solvent capacity constraint of metabolic enzymes and mitochondria, accounting for their occupied volume densities, while assuming glucose and/or fatty acid utilization. The model demonstrates that activation of aerobic glycolysis is favored above a threshold metabolic rate in both rapidly proliferating cells and heavily contracting muscles, because it provides higher ATP yield per volume density than mitochondrial oxidative phosphorylation. In the case of muscle physiology, the model also predicts that before the lactate switch, fatty acid oxidation increases, reaches a maximum, and then decreases to zero with concomitant increase in glucose utilization, in agreement with the empirical evidence. These results are further corroborated by a larger scale model, including biosynthesis of major cell biomass components. The larger scale model also predicts that in proliferating cells the lactate switch is accompanied by activation of glutaminolysis, another distinctive feature of the Warburg effect. In conclusion, intracellular molecular crowding is a fundamental constraint for cell metabolism in both rapidly proliferating- and non-proliferating cells with high metabolic demand. Addition of this constraint to metabolic flux balance models can explain several observations of mammalian cell metabolism under steady state conditions
Constraints on the pMSSM from searches for squarks and gluinos by ATLAS
We study the impact of the jets and missing transverse momentum SUSY analyses
of the ATLAS experiment on the phenomenological MSSM (pMSSM). We investigate
sets of SUSY models with a flat and logarithmic prior in the SUSY mass scale
and a mass range up to 1 and 3 TeV, respectively. These models were found
previously in the study 'Supersymmetry without Prejudice'. Removing models with
long-lived SUSY particles, we show that 99% of 20000 randomly generated pMSSM
model points with a flat prior and 87% for a logarithmic prior are excluded by
the ATLAS results. For models with squarks and gluinos below 600 GeV all models
of the pMSSM grid are excluded. We identify SUSY spectra where the current
ATLAS search strategy is less sensitive and propose extensions to the inclusive
jets search channel
Aggressive juvenile fibromatosis of the paranasal sinuses: case report and brief review
Desmoid fibromatoses are benign, slow growing fibroblastic neoplasms, arising from musculoaponeurotic stromal elements. Desmoids are characterized by local invasion, with a high rate of local recurrence and a tendency to destroy adjacent structures and organs. Desmoid fibromatoses are rare in children, and though they may occur in the head and neck region, are extremely rare in the paranasal sinuses. Here we report a case of extraabdominal desmoid fibromatosis in a seven-year-old boy involving the sphenoid sinus, one of only six published reports of desmoid fibromatosis of the paranasal sinuses. The expansile soft tissue mass eroded the walls of the sphenoid sinus as well as the posterior ethmoid air cells extending cephalad through the base of the skull. We discuss the clinicopathologic features of this lesion, including structural and ultrastructural characteristics, and we review the literature regarding treatment and outcome
Implementing GDPR in the Charity Sector: A Case Study
Due to their organisational characteristics, many charities
are poorly prepared for the General Data Protection Regulation (GDPR).
We present an exemplar process for implementing GDPR and the DPIA
Data Wheel, a DPIA framework devised as part of the case study, that
accounts for these characteristics. We validate this process and framework by conducting a GDPR implementation with a charity that works
with vulnerable adults. This charity processes both special category (sensitive) and personally identifiable data. This GDPR implementation was
conducted and devised for the charity sector, but can be equally applied
in any organisation that needs to implement GDPR or conduct DPIAs
Dispersal of Group A Streptococcal Biofilms by the Cysteine Protease SpeB Leads to Increased Disease Severity in a Murine Model
Group A Streptococcus (GAS) is a Gram-positive human pathogen best known for causing pharyngeal and mild skin infections. However, in the 1980's there was an increase in severe GAS infections including cellulitis and deeper tissue infections like necrotizing fasciitis. Particularly striking about this elevation in the incidence of severe disease was that those most often affected were previously healthy individuals. Several groups have shown that changes in gene content or regulation, as with proteases, may contribute to severe disease; yet strains harboring these proteases continue to cause mild disease as well. We and others have shown that group A streptococci (MGAS5005) reside within biofilms both in vitro and in vivo. That is to say that the organism colonizes a host surface and forms a 3-dimensional community encased in a protective matrix of extracellular protein, DNA and polysaccharide(s). However, the mechanism of assembly or dispersal of these structures is unclear, as is the relationship of these structures to disease outcome. Recently we reported that allelic replacement of the streptococcal regulator srv resulted in constitutive production of the streptococcal cysteine protease SpeB. We further showed that the constitutive production of SpeB significantly decreased MGAS5005Δsrv biofilm formation in vitro. Here we show that mice infected with MGAS5005Δsrv had significantly larger lesion development than wild-type infected animals. Histopathology, Gram-staining and immunofluorescence link the increased lesion development with lack of disease containment, lack of biofilm formation, and readily detectable levels of SpeB in the tissue. Treatment of MGAS5005Δsrv infected lesions with a chemical inhibitor of SpeB significantly reduced lesion formation and disease spread to wild-type levels. Furthermore, inactivation of speB in the MGAS5005Δsrv background reduced lesion formation to wild-type levels. Taken together, these data suggest a mechanism by which GAS disease may transition from mild to severe through the Srv mediated dispersal of GAS biofilms
Fluoxetine Counteracts the Cognitive and Cellular Effects of 5-Fluorouracil in the Rat Hippocampus by a Mechanism of Prevention Rather than Recovery
5-Fluorouracil (5-FU) is a cytostatic drug associated with chemotherapy-induced cognitive impairments that many cancer patients experience after treatment. Previous work in rodents has shown that 5-FU reduces hippocampal cell proliferation, a possible mechanism for the observed cognitive impairment, and that both effects can be reversed by co-administration of the antidepressant, fluoxetine. In the present study we investigate the optimum time for administration of fluoxetine to reverse or prevent the cognitive and cellular effects of 5-FU
A Partial Structural and Functional Rescue of a Retinitis Pigmentosa Model with Compacted DNA Nanoparticles
Previously we have shown that compacted DNA nanoparticles can drive high levels of transgene expression after subretinal injection in the mouse eye. Here we delivered compacted DNA nanoparticles containing a therapeutic gene to the retinas of a mouse model of retinitis pigmentosa. Nanoparticles containing the wild-type retinal degeneration slow (Rds) gene were injected into the subretinal space of rds+/− mice on postnatal day 5. Gene expression was sustained for up to four months at levels up to four times higher than in controls injected with saline or naked DNA. The nanoparticles were taken up into virtually all photoreceptors and mediated significant structural and biochemical rescue of the disease without histological or functional evidence of toxicity. Electroretinogram recordings showed that nanoparticle-mediated gene transfer restored cone function to a near-normal level in contrast to transfer of naked plasmid DNA. Rod function was also improved. These findings demonstrate that compacted DNA nanoparticles represent a viable option for development of gene-based interventions for ocular diseases and obviate major barriers commonly encountered with non-viral based therapies
Machine Learning Approach for Prescriptive Plant Breeding
We explored the capability of fusing high dimensional phenotypic trait (phenomic) data with a machine learning (ML) approach to provide plant breeders the tools to do both in-season seed yield (SY) prediction and prescriptive cultivar development for targeted agro-management practices (e.g., row spacing and seeding density). We phenotyped 32 SoyNAM parent genotypes in two independent studies each with contrasting agro-management treatments (two row spacing, three seeding densities). Phenotypic trait data (canopy temperature, chlorophyll content, hyperspectral reflectance, leaf area index, and light interception) were generated using an array of sensors at three growth stages during the growing season and seed yield (SY) determined by machine harvest. Random forest (RF) was used to train models for SY prediction using phenotypic traits (predictor variables) to identify the optimal temporal combination of variables to maximize accuracy and resource allocation. RF models were trained using data from both experiments and individually for each agro-management treatment. We report the most important traits agnostic of agro-management practices. Several predictor variables showed conditional importance dependent on the agro-management system. We assembled predictive models to enable in-season SY prediction, enabling the development of a framework to integrate phenomics information with powerful ML for prediction enabled prescriptive plant breeding
Challenging Masculinity in CSR Disclosures: Silencing of Women’s Voices in Tanzania’s Mining Industry
This paper presents a feminist analysis of corporate social responsibility (CSR) in a male-dominated industry within a developing country context. It seeks to raise awareness of the silencing of women’s voices in CSR reports produced by mining companies in Tanzania. Tanzania is one of the poorest countries in Africa, and women are often marginalised in employment and social policy considerations. Drawing on work by Hélène Cixous, a post-structuralist/radical feminist scholar, the paper challenges the masculinity of CSR discourses that have repeatedly masked the voices and concerns of ‘other’ marginalised social groups, notably women. Using interpretative ethnographic case studies, the paper provides much-needed empirical evidence to show how gender imbalances remain prevalent in the Tanzanian mining sector. This evidence draws attention to the dynamics faced by many women working in or living around mining areas in Tanzania. The paper argues that CSR, a discourse enmeshed with the patriarchal logic of the contemporary capitalist system, is entangled with tensions, class conflicts and struggles which need to be unpacked and acknowledged. The paper considers the possibility of policy reforms in order to promote gender balance in the Tanzanian mining sector and create a platform for women’s concerns to be voiced
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