7564 research outputs found
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Operator-Lipschitz functions on symmetrically normed ideals with non-trivial Boyd indices
No full textWe show that if the Boyd indices of a symmetrically normed ideal J of B(H) are non-trivial (differ from 1 and oo) then for any Lipschitz function f on C, the map N --> f(N) is Lipschitz on the set of normal operators with respect to the norm ||.||_J . In particular, we study ideals for which some enhanced forms of the Fuglede Theorem hold; this is necessary for the work with functions of normal operators. We also consider functions that have the property of J-stability with respect to an ideal J: if a normal operator N is perturbed by an operator X in J in such a way that the operator N +X is normal, then f(N +X) - f(N) belongs to J. As applications we present various results on Gateaux and Frechet J-differentiability of functions, and on the action of Lipschitz functions on the domains of derivations
Precision targeted cancer-associated fibroblast nano-regulator enhanced chemo-immunotherapy for triple-negative breast cancer
No full textCancer-associated fibroblasts (CAFs), major components of the triple-negative breast cancer (TNBC) tumor microenvironment, affect tumor growth and limit the therapeutic efficacy of various clinical approaches by forming a dense stromal physical barrier, inducing chemo-resistance and promoting a tumor-immunosuppressive microenvironment. Therefore, therapeutic strategies based on targeted modulation of CAFs are promising in the treatment of TNBC. However, precise targeting of CAFs faces difficulties due to the lack of specific markers for CAFs. Here, we designed a nanoparticle co-modified with anisamide and CAF cell membrane (CAFm) to load tetrandrine as a CAF nano-regulator (TET@ACNP), which is able to precisely target and modulate CAFs. Precise targeting of CAFs was achieved by the combination of the CAFm homing effect as well as the high affinity effect between anisamide and sigma receptors overexpressed on CAFs. TET@ACNP was able to inhibit CAFs activation and reduce collagen secretion, thereby breaking the physical barrier to facilitate the penetration of the first-line chemotherapeutic agent docetaxel (DTX) and the infiltration of cytotoxic T lymphocytes. In addition, TET@ACNP alleviates chemoresistance by inhibiting the Wnt/β-catenin pathway and inhibits IGF 2 expression to release the immunosuppressive microenvironment, ultimately enhancing chemotherapy effects and anti-tumor immunity. Our study proposes a comprehensive therapeutic strategy based on the precise targeting and regulation of CAFs in combination with chemotherapy to achieve multifaceted inhibition of TNBC. This is expected to be a universal platform to improve the therapeutic efficacy of different chemotherapeutic agents in various types of stroma-rich tumors
Sustainable inventory management with trapezoidal demand and amelioration under carbon regulations
No full textThis study develops a sustainable inventory model that addresses product quality variations, demand fluctuations, and shortages over a specific planning horizon. The model captures the dual dynamics of product utility evolving through concurrent growth (amelioration) and decay (deterioration). Though inspired by poultry farming, the approach applies to other quality-sensitive sectors such as aquaculture, dairy, beverages, and pharmaceuticals, emphasizing its relevance for diverse perishable supply chains. The model integrates a trapezoidal demand function, Weibull amelioration and deterioration, and a carbon cap and tax policy to optimize replenishment decisions while promoting environmental sustainability. A nonlinear continuous costing optimization method is developed, incorporating Weibull’s instantaneous deterioration and amelioration effects. The Black Hole Algorithm and Quasi-Newton method are employed to solve for optimal order quantities and replenishment cycles. Numerical simulations and sensitivity analysis evaluate the impact of crucial parameters on inventory performance. Results indicate moderate improvement reduces holding costs, while uncontrolled growth leads to overstock and elevated carbon penalties. The carbon cap-and-tax policy also efficiently abates emissions while maintaining cost efficiency, highlighting the necessity for a balanced replenishment strategy for sustainable operations. This research contributes a unified framework integrating biological dynamics, demand variability, environmental regulations, and hybrid optimization for sustainable, cost-effective inventory management
Nanosized natural products for immune dysregulation: a systematic review of mechanisms, therapeutic applications, and translational challenges
No full textBackground:
Natural products possess remarkable bidirectional immunomodulatory properties, offering great promise for treating diseases characterized by immune dysregulation, such as cancer and inflammation. However, poor solubility, accelerated metabolism, and the lack of tissue specificity hinder their clinical translation. Nanotechnology has emerged as a powerful strategy to overcome these intrinsic limitations, enhancing the bioavailability and therapeutic potential of natural products.
Purpose:
To evaluate how nanosized natural products overcome these barriers to enhance the immunoregulatory efficacy of natural products. Also to summarise their mechanisms and therapeutic advantages with a view to elaborating on future translational challenges.
Methods:
All the relevant clinical and research studies conducted on the application and efficacy of nanosized natural products in immune dysregulation diseases were included, as retrieved from PubMed, Web of Science, ScienceDirect, and Google Scholar, following the use of specific search terms.
Results:
This review systematically evaluates important advancements in nanosized natural products-based immunomodulators, including nano drugs and vaccine adjuvants. By integrating evidence from in vitro, in vivo, and clinical studies, we highlight how nanosized natural products protect biologically active substance, prolong immune responses, enable targeted delivery, and alleviate toxic side effects. We have discussed the mechanisms by which these nanosized natural products modulate key immunosuppressive components, including T lymphocytes, dendritic cells, macrophages, natural killer cells, and neutrophils, to restore equilibrium to homeostasis. The use of nanosized natural products in the enhancement of cancer immunotherapy and their ameloriaton of concomitant inflammatory diseases is also discussed extensively.
Conclusion:
Nanosized natural products represent a transformative approach for precise immunomodulation. They bridge the gap between the therapeutic potential of natural compounds and clinical application. Future success hinges on addressing challenges in scalable manufacturing, long-term toxicology, and designing smarter stimuli-responsive delivery systems
Postural stability in cyclists
Full text linkAim:
Age-related loss of postural stability (or balance) is a main contributing factor to hospital admissions for falls in the elderly, with a sharp decline in balance starting in the fifth decade of life. Core stability exercises have been well documented as having a positive effect on balance, but the effect of cycling on balance has not been widely considered. With the continued increase in uptake of recreational cycling this investigation could offer valuable insight, with implications for fall risk reduction in later life. The progression of portable technology offers opportunity to transfer clinical balance testing to the field. The study used the SWAY™ app on a mobile phone to investigate balance in two different disciplines of recreational cycling - road cycling (RC) and mountain biking (MTB). It aimed to ascertain whether cycling promotes better balance as compared with an age-matched sedentary control (CN), and which cycling discipline promotes the better balance.
Methods:
42 adults (53 ± 7 y), RC N = 14, MTB N = 14, and CN N = 14, balanced with eyes closed in five stances as instructed by the SWAY app on a mobile phone held to the chest, which gave the mean of five stances as a total balance score.
Results:
RC had significantly better balance than CN (p <0.001); MTB had significantly better balance than CN (p = 0.004); RC had significantly better balance than MTB (p = 0.046).
Conclusion:
MTB balance was worse than RC balance, but both cycling groups were found to have better balance scores than the control. These findings have implications for public health, as cycling, an inexpensive and accessible activity already known to offer substantial health benefits, could additionally help maintain postural stability and potentially reduce risk of falls in later life
Vile sovereignty: the carnival of power
Full text linkIn this paper we seek to extend Bakhtin’s reading of the folk carnival and apply it to help understand the carnivalesque, performative aspects of state power. Drawing on the work of Agamben, Foucault, Lacan and Žižek and recent scholarship on the role of laughter in the Stalinist totalitarian culture, we argue that the state can also laugh and that it can have its own carnival tradition as well. To explore what we propose to call the carnival of power, we examine three iterations of this tradition: the festive exercise of state violence, state carnivalisers, and the carnivalesque style in governance
Qualitative analysis of migrants' network data: using conceptual reflexivity to reveal the 'magic trick'
Full text linkWhile in recent years, qualitative social network analysis (SNA) has advanced considerably – particularly in migration research – there is still an overall tendency to focus more on issues of network structure and on the generation of data, rather than on how data can be interpreted and analysed qualitatively in practice. In this article, we discuss how a genuinely qualitative SNA should not only apply qualitative techniques in generating visual and oral network data but also in the analytical processes. Building on our earlier work, we advance methodological debates by presenting the idea of ‘conceptual reflexivity’: an awareness of how our thinking about networks and the ways in which we interact with participants – and the wider field – inform layers of meaning making. Using two recent examples from our migration research, we explore the inter‐subjectivity of the research encounter, offering insights into the ‘craft’ of qualitative SNA and the epistemological issues underpinning it. In doing so, we aim to make analytical processes more open and visible, to reveal, so to speak, what goes on behind the curtain: the ‘magic trick’ of how qualitative SNA is performed
When long lost siblings reunite: populism, conservatism and the discontents of progress
Full text linkAlthough in recent years populism has emerged from within mainstream conservative parties around the world, populism and conservatism are still rarely studied together. Connecting them may appear paradoxical, given their opposing ideational content, as populism mobilizes the people against the elites while conservatism defends established hierarchies and traditions. This article argues however that we can identify many more similarities and overlaps between populism and conservatism if we adopt a broader conceptualization of political ideologies that includes not only their ideational content, but also their discursive, strategic, organizational and structural dimensions. On this basis, the article views populism and conservatism as modes of politics that mobilize followers primarily on the basis of idealized visions of the political community and state-society relations. Although populism puts forth an antagonistic vision of these relations and conservatism a deferential one, both are otherwise quite similar as strategies aimed at defining the boundaries and character of the political community on the basis of its relationship with political authority. The article conducts an empirical probe demonstrating how its theoretical argument can be applied in comparative research
The dietetic practice of prescribing amino acid-based formulas in paediatrics patients without cow’s milk allergy: a single centre retrospective study
Full text linkBackground & aims:
Although there is a comprehensive pathway for prescribing amino acid-based (elemental) formulas (AAF) in paediatric patients with cow’s milk allergy (CMA), there is a paucity of evidence-based practice for prescribing AAFs in patients without CMA. Gastrointestinal symptoms are some complications that can occur in enteral tube-fed patients, to mitigate these symptoms an AAF may be prescribed. AAFs contain macronutrients that have been enzymatically hydrolysed, requiring minimal digestion and promoting optimal absorption. The primary aim of this retrospective study was to ascertain the dietetic practice of prescribing AAFs to enteral tube-fed paediatric patients without CMA. Secondary outcomes measured weight change at 1 month and 6 months after AAF was prescribed and the incidence of hypophosphatemia at 6 months.
Methods:
This is a single-centre, retrospective review of paediatric patients prescribed an AAF at a tertiary paediatric hospital between July 2023 and July 2024. Ethical approval was granted by ANONYMISED Audit, Quality Improvement and Service Evaluation Committee: registration number GOSH2024/3834. Inclusion criteria were patients aged between 0 and 16 years old who had been prescribed an AAF as part of their enteral nutrition, providing at least 80% of their estimated energy requirements for any condition other than allergic disease. Exclusion criteria were patients with confirmed immunoglobulin (Ig)E or non-IgE mediated CMA or multiple food allergies, eosinophilic gastrointestinal disease, and Food protein-induced enterocolitis syndrome. Data were collected on demographics, anthropometrics, feed regimens, gastrointestinal symptoms, proton pump inhibitor use and serum phosphate concentration
Results:
203 children were prescribed an AAF during the data collection period, of these, 154 of 203 (76%) patients had no allergies. Patients with gastrointestinal symptoms were the most common reason for commencing an AAF, 76 of 154 (49%) patients. The median age of patients prescribed AAF was 5.5 (IQR 1.3-9.8) years old. Patients displaying upper or lower gastrointestinal symptoms were the most common reason dietitians prescribed an AAF, 76 of 154 (49%) patients. 44 of 154 (28%) patients prescribed an AAF had a neurological impairment as a primary diagnosis. Dietitians prescribed AAFs as a first-line formula to transition patients off parenteral nutrition in 26 of 154 (17%) patients. 23 of 154 (15%) patients were prescribed an AAF after developing mucositis post high-dose chemotherapy. AAF was also prescribed in patients post cardiac and gastrointestinal surgery, protein-losing enteropathy, and gastrointestinal dystonia. The mean weight-for-age Z-score significantly improved in patients prescribed AAF from -3.7 (1.6SD) at baseline to -2.5 (1.5SD) at 6 months (p-value 0.001). After 6 months of receiving an AAF, there was no increased probability of hypophosphatemia in patients prescribed proton pump inhibitors. (p-value 0.84).
Conclusions:
This single-centre retrospective study found that paediatric dietitians reserved the prescription of AAFs for patients with complex neurological and gastrointestinal conditions. The most common reason for dietitians to prescribe AAFs was to mitigate upper and lower gastrointestinal symptoms in patients already established on enteral formulas. This review found that medically complex patients receiving AAFs for 6 months achieved expected weight gain while under the supervision of a dietitian. Our study was unable to substantiate an increased probability of hypophosphatemia in patients prescribed proton pump inhibitors and an AAF. All paediatric patients with complex medical conditions who need long-term enteral nutritional support require close nutritional monitoring
Establishment of an experimental system to analyse extracellular vesicles during apoplastic fungal pathogenesis
Full text linkPhoma stem canker disease of oilseed rape (Brassica napus) is caused by the extracellular fungal pathogen Leptosphaeria maculans. Although this pathogen resides exclusively in apoplastic spaces surrounding plant cells, the significance of extracellular vesicles (EVs) has not been assessed. Here, we show a method to collect apoplastic fluids (AFs) from infected leaves or cotyledons for collection of EVs during the process of host colonisation. The 15,000 × g supernatants of AFs were shown to contain ribulose-bisphosphate carboxylase (RuBisCO) at 7 days post-inoculation with L. maculans, a protein that was absent from unchallenged cotyledons. RuBisCO release coincided with the switch from biotrophy to necrotrophy, suggesting the involvement of host cell death. However, RuBisCO release did not differ between compatible and incompatible interactions, suggesting necrotrophic host cell death might not be the only process involved. EVs were also collected from axenic fungal cultures and characterised for their particle size distribution using nanoparticle tracking analysis and transmission electron microscopy. The protein composition of EV-enriched fractions was analysed using SDS-PAGE and proteomics. Enrichment analysis of gene ontology terms provided evidence for involvement of glucan and chitin metabolism as well as catalase and peptidase activities. Most of the proteins identified have previously been found in EV studies and/or EV databases, and for most of the proteins evidence was found for an involvement in pathogenicity/virulence