This paper investigates the contribution of massive star clusters (MSCs) as sources of high-energy gamma-rays and their impact on the ultra-high-energy emission observed throughout the Galaxy. By modelling proton injection, the study explores how the acceleration of protons in MSCs contributes to the gamma radiation detectable from Earth. The analysis focuses on two primary types of clusters: widespread, dispersed clusters and younger, compact massive clusters, both of which host shock waves generated by supernova remnants. Clusters located near the Solar system, within a 3-kpc radius, are identified. Analytical methods are used to calculate energy spectra and gamma-ray production rates. The findings suggest that young and compact MSCs contribute to multi-TeV to PeV gamma-ray emission, with the dominant contribution arising from nearby populations.
Trans-Chalcone (TC) is an anti-inflammatory flavonoid that reduces hyperalgesia by targeting nuclear factor κB and inflammasome in gout arthritis model. However, a direct modulation of nociceptors by TC has never been investigated, which was the aim of the present study. Experimental models of overt pain-like behaviors were applied as the stimuli-induced behavior depends, at least in part, on nociceptive neuron activation by the stimuli themselves making them suitable to investigate if a drug candidate can inhibit nociceptive neuron activation. The selected models involve transient receptor potential (TRP) vanilloid 1 (V1)+ and TRP ankyrin 1 (A1)+ nociceptive neuron activation. TC (10 mg/kg, per oral, 30 min pretreatment) inhibited abdominal contortions induced by acetic acid (58.8
Urban PM2.5 samples were collected in Manaus, a major city in the Amazon rainforest, to analyze dicarboxylic acids (DCA) (C2-C9), black carbon (BC), levoglucosan (LEV), and sulfate (SO4 2-) during daytime and nighttime, in periods with and without smoke over the city from biomass burning (BB). Oxalic acid (C2) was the dominant DCA, followed by malonic acid (C3) and succinic acid (C4). The 12.5% nighttime increase in oxalic acid (C2) and higher C2/TDCA ratio at night indicate ongoing secondary formation, not just accumulation from a lower boundary layer. BC showed a moderate correlation with C4, and, since no correlation was observed between BC and LEV, this suggests that fossil fuel combustion-a recognized source of BC-is one of the possible primary sources of C4 in the studied atmosphere. The phthalic acid (Ph) to azelaic acid (C9) ratio (Ph/C9), an indicator of the dominant oxidative pathway for DCA formation, was lowest at night, and C9 exhibited a strong correlation with levoglucosan (LEV) (r = 0.89), suggesting that BB serves as a major source of primary C9 and may also provide precursors that contribute to the secondary formation of PM2.5. During smoke periods, LEV increased by 479%, while C2 and C3 increased by 247% and 259%, and the ratios of C2/C4 and C2/SO4 2- increased by 40% and 259%, respectively. Biomass burning has modified the composition of DCAs, possibly influencing aerosol hygroscopicity and their potential to act as cloud condensation nuclei, with possible implications for regional climate. This study highlights the critical role of biomass burning in the formation of organic aerosols and their influence on oxidative pathways, as well as their broader environmental impacts. This study shows biomass burning increases dicarboxylic acids in Manaus air, altering aerosol formation and composition, impacting urban air quality and atmospheric processes in the Amazon region.
1001 Background: Imlunestrant (imlu) is a next-generation, brain-penetrant, oral selective estrogen receptor degrader. The EMBER-3 trial, in patients (pts) with ER+, HER2- ABC who had disease progression on or after aromatase inhibitor-based therapy, showed significant progression free survival (PFS) improvement with imlu vs standard therapy (SOC, fulvestrant or exemestane) in pts with ESR1 mutations ( ESR1 m), and with imlunestrant+abemaciclib (imlu+abema) vs imlu in all pts, regardless of ESR1 m. Exploratory PRO analyses are presented here. Methods: EORTC QLQ-C30 was administered at baseline (BL) and every 8 weeks until treatment discontinuation. Prespecified QLQ-C30 analysis used a longitudinal mixed model for repeated measures to calculate mean change from BL in pts with BL and ≥1 post-BL score. PRO-CTCAE (diarrhea frequency) was administered weekly, reporting 0 (never) to 4 (almost constantly). PRO-CTCAE (injection site reaction [ISR]) was administered to fulvestrant recipients weekly for 2 weeks post-injection, reporting yes/no (pain, swelling, redness). Descriptive analysis was used for PRO-CTCAE. Results: In pts with ESR1 m, imlu monotherapy was associated with many improved or maintained EORTC QLQ-C30 scores, whereas scores with SOC were declined or maintained. Specifically, pts with ESR1 m on imlu had improved global health status (GHS)/quality of life (QOL) and physical function (PF) scores, while scores with SOC declined (mean change differences between treatments: 9.9 [0.1, 19.7] and 6.2 [-0.8, 13.1], respectively). These PRO findings mirror the PFS findings in this group. In the overall population, GHS/QOL scores declined similarly with imlu vs SOC (mean change differences: 0.5 [-4.7, 5.7]), while PF scores were maintained with imlu vs a slight decline with SOC (mean change difference: 2.5 [-1.1, 6.1]). Most fulvestrant recipients (72%) reported ISR at any time while on treatment, with a mean of 31% during the first week of the first 6 cycles. Imlu+abema vs imlu showed broadly similar declines in all pts, with minimal mean change differences in GHS/QOL and PF scores (0.8 [-7.4, 5.9]; -2.2 [-6.6, 2.2], respectively). Pts reported similarly low rates of “frequent” or “almost constant” diarrhea with imlu (3%) and SOC (2%) and higher rates with imlu+abema (22%). Conclusions: PROs from EMBER-3 demonstrated that patients with ESR1 m had better GHS/QOL and PF with imlu vs SOC, mirroring efficacy results. While the frequency of CTCAE defined ISRs was low, the high rate of PRO-CTCAE ISR demonstrates that this clinically relevant adverse event is underappreciated by physicians. Additionally, all pts had generally comparable GHS/QOL and PF with imlu+abema vs imlu. Overall, these results support the efficacy and safety of imlu compared to existing SOC. Clinical trial information: NCT04975308 .
In this paper, we consider a thermoelastic plate of Green-Lindsay type, characterized by two relaxation times and exhibiting finite-speed heat waves. The homogeneous problem was recently studied by Quintanilla et al. (2023). They pointed out that it was not known whether the domain of the semigroup generator is compactly embedded into the energy space. Nevertheless, through a detailed analysis, they established the well-posedness of the system and the exponential stability of its solution semigroup. Our aim is to investigate the asymptotic dynamics of the plate in the presence of a nonlinear foundation. We establish the existence of a finite dimensional global attractor with higher regularity.
