656 research outputs found
Drum vortons in high density QCD
Recently it was shown that high density QCD supports of number of topological
defects. In particular, there are U(1)_Y strings that arise due to K^0
condensation that occurs when the strange quark mass is relatively large. The
unique feature of these strings is that they possess a nonzero K^+ condensate
that is trapped on the core. In the following we will show that these strings
(with nontrivial core structure) can form closed loops with conserved charge
and currents trapped on the string worldsheet. The presence of conserved
charges allows these topological defects, called vortons, to carry angular
momentum, which makes them classically stable objects. We also give arguments
demonstrating that vortons carry angular momentum very efficiently (in terms of
energy per unit angular momentum) such that they might be the important degrees
of freedom in the cores of neutron stars.Comment: 11 pages, accepted for publication in Physical Review
Fitting the integrated Spectral Energy Distributions of Galaxies
Fitting the spectral energy distributions (SEDs) of galaxies is an almost
universally used technique that has matured significantly in the last decade.
Model predictions and fitting procedures have improved significantly over this
time, attempting to keep up with the vastly increased volume and quality of
available data. We review here the field of SED fitting, describing the
modelling of ultraviolet to infrared galaxy SEDs, the creation of
multiwavelength data sets, and the methods used to fit model SEDs to observed
galaxy data sets. We touch upon the achievements and challenges in the major
ingredients of SED fitting, with a special emphasis on describing the interplay
between the quality of the available data, the quality of the available models,
and the best fitting technique to use in order to obtain a realistic
measurement as well as realistic uncertainties. We conclude that SED fitting
can be used effectively to derive a range of physical properties of galaxies,
such as redshift, stellar masses, star formation rates, dust masses, and
metallicities, with care taken not to over-interpret the available data. Yet
there still exist many issues such as estimating the age of the oldest stars in
a galaxy, finer details ofdust properties and dust-star geometry, and the
influences of poorly understood, luminous stellar types and phases. The
challenge for the coming years will be to improve both the models and the
observational data sets to resolve these uncertainties. The present review will
be made available on an interactive, moderated web page (sedfitting.org), where
the community can access and change the text. The intention is to expand the
text and keep it up to date over the coming years.Comment: 54 pages, 26 figures, Accepted for publication in Astrophysics &
Space Scienc
Dimensionless cosmology
Although it is well known that any consideration of the variations of
fundamental constants should be restricted to their dimensionless combinations,
the literature on variations of the gravitational constant is entirely
dimensionful. To illustrate applications of this to cosmology, we explicitly
give a dimensionless version of the parameters of the standard cosmological
model, and describe the physics of Big Bang Neucleosynthesis and recombination
in a dimensionless manner. The issue that appears to have been missed in many
studies is that in cosmology the strength of gravity is bound up in the
cosmological equations, and the epoch at which we live is a crucial part of the
model. We argue that it is useful to consider the hypothetical situation of
communicating with another civilization (with entirely different units),
comparing only dimensionless constants, in order to decide if we live in a
Universe governed by precisely the same physical laws. In this thought
experiment, we would also have to compare epochs, which can be defined by
giving the value of any {\it one} of the evolving cosmological parameters. By
setting things up carefully in this way one can avoid inconsistent results when
considering variable constants, caused by effectively fixing more than one
parameter today. We show examples of this effect by considering microwave
background anisotropies, being careful to maintain dimensionlessness
throughout. We present Fisher matrix calculations to estimate how well the fine
structure constants for electromagnetism and gravity can be determined with
future microwave background experiments. We highlight how one can be misled by
simply adding to the usual cosmological parameter set
Novel Perspectives in Management of Angiogenesis and Cancer Therapy
Funding: The project was funded by IPOLFG EPE and by iNOVA4Health (UID/Multi/04462/2019) a program financially supported by Fundação para a Ciência e Tecnologia (FCT)/Ministério da Educação e Ciência, through national funds. We also acknowledge funding from FCT-MCTES through the project DREAM—PTDC/MEC-ONC/29327/2017. FL-C PhD fellowship was funded by FCT (PD/BD/128337/2017).The activation of endothelial cells (ECs) is a crucial step on the road map of tumor angiogenesis and expanding evidence indicates that a pro-oxidant tumor microenvironment, conditioned by cancer metabolic rewiring, is a relevant controller of this process. Herein, we investigated the contribution of oxidative stress-induced ferroptosis to ECs activation. Moreover, we also addressed the anti-angiogenic effect of Propranolol. We observed that a ferroptosis-like mechanism, induced by xCT inhibition with Erastin, at a non-lethal level, promoted features of ECs activation, such as proliferation, migration and vessel-like structures formation, concomitantly with the depletion of reduced glutathione (GSH) and increased levels of oxidative stress and lipid peroxides. Additionally, this ferroptosis-like mechanism promoted vascular endothelial cadherin (VE-cadherin) junctional gaps and potentiated cancer cell adhesion to ECs and transendothelial migration. Propranolol was able to revert Erastin-dependent activation of ECs and increased levels of hydrogen sulfide (H2S) underlie the mechanism of action of Propranolol. Furthermore, we tested a dual-effect therapy by promoting ECs stability with Propranolol and boosting oxidative stress to induce cancer cell death with a nanoformulation comprising selenium-containing chrysin (SeChry) encapsulated in a fourth generation polyurea dendrimer (SeChry@PUREG4). Our data showed that novel developments in cancer treatment may rely on multi-targeting strategies focusing on nanoformulations for a safer induction of cancer cell death, taking advantage of tumor vasculature stabilization.publishersversionpublishe
Metabolic profiling and combined therapeutic strategies unveil the cytotoxic potential of selenium-chrysin (SeChry) in NSCLC cells
Funding Information: The institutions are funded by Fundac\u00B8 \u00E3o para a Ci\u00EAncia e a Tecnologia/Minist\u00E9rio da Ci\u00EAncia, Tecnologia e Ensino Superior (FCT/MCTES, Portugal) through national funds to iNO-VA4Health [grant numbers UIDB/04462/2020 and UIDP/04462/2020], to MOSTMICRO-ITQB [grant numbers UIDB/04612/2020 and UIDP/04612/2020] and the Associated Laboratory LS4FUTURE [grant number LA/P/0087/2020]. During the course of PhD, Cindy Mendes was funded by Liga Portuguesa Contra o Cancro -Nucleo regional Sul (LPCC-NRS) and by an FCT individual Ph.D. fellowship [grant number 2020.06956.BD]. Isabel Lemos was funded by an FCT individual Ph.D. fellowship [grant number UI/BD/154203/2022]. Ana Hip\u00F3lito was funded by a FCT individual Ph.D. fellowship [grant number SFRH/BD/148441/2019]. Filipa Martins was funded by a FCT individual Ph.D. fellowship (2020.04780.BD). Luis G. Gonc\u00B8 alves was financed by a FCT contract according to DL57/2016, [grant number SFRH/BPD/111100/2015]. This work benefited from access to CERMAX, ITQB-NOVA, Oeiras, Portugal with equipment funded by FCT, project AAC 01/SAICT/2016. Publisher Copyright: © 2024 The Author(s).Lung cancer ranks as the predominant cause of cancer-related mortalities on a global scale. Despite progress in therapeutic interventions, encompassing surgical procedures, radiation, chemotherapy, targeted therapies and immunotherapy, the overall prognosis remains unfavorable. Imbalances in redox equilibrium and disrupted redox signaling, common traits in tumors, play crucial roles in malignant progression and treatment resistance. Cancer cells, often characterized by persistent high levels of reactive oxygen species (ROS) resulting from genetic, metabolic, and microenvironmental alterations, counterbalance this by enhancing their antioxidant capacity. Cysteine availability emerges as a critical factor in chemoresistance, shaping the survival dynamics of non-small cell lung cancer (NSCLC) cells. Selenium-chrysin (SeChry) was disclosed as a modulator of cysteine intracellular availability. This study comprehensively characterizes the metabolism of SeChry and investigates its cytotoxic effects in NSCLC. SeChry treatment induces notable metabolic shifts, particularly in selenocompound metabolism, impacting crucial pathways such as glycolysis, gluconeogenesis, the tricarboxylic acid (TCA) cycle, and amino acid metabolism. Additionally, SeChry affects the levels of key metabolites such as acetate, lactate, glucose, and amino acids, contributing to disruptions in redox homeostasis and cellular biosynthesis. The combination of SeChry with other treatments, such as glycolysis inhibition and chemotherapy, results in greater efficacy. Furthermore, by exploiting NSCLC’s capacity to consume lactate, the use of lactic acid-conjugated dendrimer nanoparticles for SeChry delivery is investigated, showing specificity to cancer cells expressing monocarboxylate transporters.publishersversionpublishe
Serum hepcidin levels in cognitively normal older adults with high neocortical Amyloid-β load
Background/Objective:
Hepcidin, an iron-regulating hormone, suppresses the release of iron by binding to the iron exporter protein, ferroportin, resulting in intracellular iron accumulation. Given that iron dyshomeostasis has been observed in Alzheimer’s disease (AD) together with elevated serum hepcidin levels, the current study examined whether elevated serum hepcidin levels are an early event in AD pathogenesis by measuring the hormone in cognitively normal older adults at risk of AD, based on high neocortical amyloid-β load (NAL).
Methods:
Serum hepcidin levels in cognitively normal participants (n = 100) aged between 65–90 years were measured using ELISA. To evaluate NAL, all participants underwent 18F-florbetaben positron emission tomography. A standard uptake value ratio (SUVR)<1.35 was classified as low NAL (n = 65) and ≥1.35 (n = 35) was classified as high NAL.
Results:
Serum hepcidin was significantly higher in participants with high NAL compared to those with low NAL before and after adjusting for covariates: age, gender, and APOE ɛ4 carriage (p < 0.05). A receiver operating characteristic curve based on a logistic regression of the same covariates, the base model, distinguished high from low NAL (area under the curve, AUC = 0.766), but was outperformed when serum hepcidin was added to the base model (AUC = 0.794) and further improved with plasma Aβ42/40 ratio (AUC = 0.829).
Conclusion:
The present findings indicate that serum hepcidin is increased in individuals at risk for AD and contribute to the body of evidence supporting iron dyshomeostasis as an early event of AD. Further, hepcidin may add value to a panel of markers that contribute toward identifying individuals at risk of AD; however, further validation studies are required
Criptococose cutânea associada à severa infestação por Sarcoptes sp. e Demodex sp. em um cão
Systemic perturbations of the kynurenine pathway precede progression to dementia independently of amyloid-β
Increasing evidence suggests that kynurenine pathway (KP) dyshomeostasis may promote disease progression in dementia. Studies in Alzheimer's disease (AD) patients confirm KP dyshomeostasis in plasma and cerebrospinal fluid (CSF) which correlates with amyloid-β and tau pathology. Herein, we performed the first comprehensive study assessing baseline levels of KP metabolites in participants enrolling in the Australian Imaging Biomarkers Flagship Study of Aging. Our purpose was to test the hypothesis that changes in KP metabolites may be biomarkers of dementia processes that are largely silent. We used a cross-sectional analytical approach to assess non-progressors (N = 73); cognitively normal (CN) or mild cognitive impairment (MCI) participants at baseline and throughout the study, and progressors (N = 166); CN or MCI at baseline but progressing to either MCI or AD during the study. Significant KP changes in progressors included increased 3-hydroxyanthranilic acid (3-HAA) and 3-hydroxyanthranilic acid/anthranilic acid (3-HAA/AA) ratio, the latter having the largest effect on the odds of an individual being a progressor (OR 35.3; 95% CI between 14 and 104). 3-HAA levels were hence surprisingly bi-phasic, high in progressors but low in non-progressors or participants who had already transitioned to MCI or dementia. This is a new, unexpected and interesting result, as most studies of the KP in neurodegenerative disease show reduced 3-HAA/AA ratio after diagnosis. The neuroprotective metabolite picolinic acid was also significantly decreased while the neurotoxic metabolite 3-hydroxykynurenine increased in progressors. These results were significant even after adjustment for confounders. Considering the magnitude of the OR to predict change in cognition, it is important that these findings are replicated in other populations. Independent validation of our findings may confirm the utility of 3-HAA/AA ratio to predict change in cognition leading to dementia in clinical settings
CURVAS DE DESSORÇÃO E CALOR LATENTE DE VAPORIZAÇÃO PARA AS SEMENTES DE MILHO PIPOCA (Zea mays)
RESUMO O objetivo deste trabalho foi determinar as curvas de umidade de equilíbrio higroscópico e o calor latente de vaporização para as sementes de milho pipoca (Zea mays). O teor de umidade inicial das sementes era 23% b.u. As sementes foram submetidas a dessorção, sob diversas condições de temperatura (20, 30, 40 e 50°C) e umidade relativa do ar (30, 40, 50, 60, 70, 80 e 90%) com três repetições, até atingirem a umidade de equilíbrio. A temperatura e a umidade relativa do ar foram controladas por meio de uma unidade condicionadora de ar "Aminco-Air". Os seguintes modelos matemáticos foram ajustados aos dados experimentais: Henderson, Henderson modificado, Chung-Pfost, Copace e Sigma-Copace; as constantes dessas equações foram obtidas por regressão, enquanto o calor latente de vaporização foi calculado utilizando-se a equação de Henderson modificada, estimando-se uma equação empírica para calcular o calor latente de vaporização para o milho pipoca, em função da temperatura e do teor de umidade do grão. De acordo com os resultados obtidos concluiu-se que as equações de Copace e Sigma-Copace foram as que melhor se ajustaram aos dados experimentais, em todas as faixas estudadas de temperatura e umidade relativa do ar, podendo ser utilizadas para se calcular a umidade de equilíbrio das sementes de milho pipoca. A equação empírica determinada para calcular o calor latente de vaporização da água dos grãos do milho pipoca mostrou-se adequada
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