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Dense gas in minihalos with masses of 106−108 M ⊙ can shield themselves from reionization for ∼100 Myr after being exposed to the UV background. These self-shielded systems, often unresolved in cosmological simulations, can introduce strong absorption in quasar spectra. This paper is the first systematic study on the impact of these systems on the Lyα forest. We first derive the H i column density profile of photoevaporating minihalos by conducting 1D radiation-hydrodynamics simulations. We utilize these results to estimate the Lyα opacity from minihalos in a large-scale simulation that cannot resolve self-shielding. When the ionization rate of the background radiation is 0.03 × 10−12 s−1, as expected near the end of reionization at z ∼ 5.5, we find that the incidence rate of damped Lyα absorbers increases by a factor of ∼2−4 compared to at z = 4.5. The Lyα flux is, on average, suppressed by ∼3% of its mean due to minihalos. The absorption features enhance the 1D power spectrum up to ∼5% at k ∼ 0.1 h Mpc−1 (or 10−3 km−1 s), which is comparable to the enhancement caused by inhomogeneous reionization. The flux is particularly suppressed in the vicinity of large halos along the line-of-sight direction at separations of up to 10 h −1 Mpc at r ⊥ ≲ 2 h −1 Mpc. However, these effects become much smaller for higher ionizing rates (≳0.3 × 10−12 s−1) expected in the post-reionization Universe. Our findings highlight the need to consider minihalo absorption when interpreting the Lyα forest at z ≳ 5.5. Moreover, the sensitivity of these quantities to the ionizing background intensity can be exploited to constrain the intensity itself.

CMB-S4 - the next-generation ground-based cosmic microwave background (CMB) experiment - is set to significantly advance the sensitivity of CMB measurements and enhance our understanding of the origin and evolution of the universe. Among the science cases pursued with CMB-S4, the quest for detecting primordial gravitational waves is a central driver of the experimental design. This work details the development of a forecasting framework that includes a power-spectrum-based semianalytic projection tool, targeted explicitly toward optimizing constraints on the tensor-to-scalar ratio, r, in the presence of Galactic foregrounds and gravitational lensing of the CMB. This framework is unique in its direct use of information from the achieved performance of current Stage 2-3 CMB experiments to robustly forecast the science reach of upcoming CMB-polarization endeavors. The methodology allows for rapid iteration over experimental configurations and offers a flexible way to optimize the design of future experiments, given a desired scientific goal. To form a closed-loop process, we couple this semianalytic tool with map-based validation studies, which allow for the injection of additional complexity and verification of our forecasts with several independent analysis methods. We document multiple rounds of forecasts for CMB-S4 using this process and the resulting establishment of the current reference design of the primordial gravitational-wave component of the Stage-4 experiment, optimized to achieve our science goals of detecting primordial gravitational waves for r > 0.003 at greater than 5σ, or in the absence of a detection, of reaching an upper limit of r < 0.001 at 95% CL.

Pedro Jara-Guajardo,1,2 Francisco Morales-Zavala,1,2 Karen Bolaños,1– 3 Ernest Giralt,4,5 Eyleen Araya,2,6 Gerardo A Acosta,7,8 Fernando Albericio,5,7,9 Alejandra R Alvarez,10 Marcelo J Kogan1,2 1Departamento de Quimica Farmacologica y Toxicologica, Facultad de Ciencias Quimicas y Farmaceuticas, Universidad de Chile, Santiago, Chile; 2Advanced Center for Chronic Diseases (ACCDiS), Independencia, Santiago, Chile; 3Center for Studies on Exercise, Metabolism and Cancer (CEMC), Laboratory of Cellular Communication, Program of Cell and Molecular Biology, Faculty of Medicine, Institute of Biomedical Sciences (ICBM), University of Chile, Santiago, Chile; 4Institute for Research in Biomedicine (IRB Barcelona), Barcelona Institute of Science and Technology (BIST), Barcelona, Spain; 5Department of Inorganic and Organic Chemistry, University of Barcelona, Barcelona, Spain; 6Departamento de Ciencias Quimicas, Facultad de Ciencias Exactas, Universidad Andres Bello, Santiago, Chile; 7CIBER-BBN, Networking Centre on Bioengineering, Biomaterials and Nanomedicine & Department of Organic Chemistry, University of Barcelona, Barcelona, Spain; 8Institute for Advanced Chemistry of Catalonia (IQAC-CSIC), Barcelona, 08034, Spain; 9School of Chemistry & Physics, University of KwaZulu-Natal, Durban, South Africa; 10Cell Signaling Laboratory, Department of Cellular and Molecular Biology, Biological Sciences Faculty, Millennium Institute on Immunology and Immunotherapy, Pontificia Universidad Católica de Chile, Santiago, ChileCorrespondence: Alejandra R Alvarez; Marcelo J Kogan, Email aalvarez@bio.puc.cl; mkogan@ciq.uchile.clIntroduction: The development of new materials and tools for radiology is key to the implementation of this diagnostic technique in clinics. In this work, we evaluated the differential accumulation of peptide-functionalized GNRs in a transgenic animal model (APPswe/PSENd1E9) of Alzheimer’s disease (AD) by computed tomography (CT) and measured the pharmacokinetic parameters and bioaccumulation of the nanosystem.Methods: The GNRs were functionalized with two peptides, Ang2 and D1, which conferred on them the properties of crossing the blood-brain barrier and binding to amyloid aggregates, respectively, thus making them a diagnostic tool with great potential for AD. The nanosystem was administered intravenously in APPswe/PSEN1dE9 model mice of 4-, 8- and 18-months of age, and the accumulation of gold nanoparticles was observed by computed tomography (CT). The gold accumulation and biodistribution were determined by atomic absorption.Results: Our findings indicated that 18-month-old animals treated with our nanosystem (GNR-D1/Ang2) displayed noticeable differences in CT signals compared to those treated with a control nanosystem (GNR-Ang2). However, no such distinctions were observed in younger animals. This suggests that our nanosystem holds the potential to effectively detect AD pathology.Discussion: These results support the future development of gold nanoparticle-based technology as a more effective and accessible alternative for the diagnosis of AD and represent a significant advance in the development of gold nanoparticle applications in disease diagnosis. Keywords: computed tomography, gold nanorods, amyloid-beta, Aβ, Alzheimer’s disease, diagnostic

Since 2014, Brazil has experienced an unprecedented epidemic caused by chikungunya virus (CHIKV), with several waves of East-Central-South-African (ECSA) lineage transmission reported across the country. In 2018, Rio de Janeiro state, the third most populous state in Brazil, reported 41% of all chikungunya cases in the country. Here we use evolutionary and epidemiological analysis to estimate the timescale of CHIKV-ECSA-American lineage and its epidemiological patterns in Rio de Janeiro. We show that the CHIKV-ECSA outbreak in Rio de Janeiro derived from two distinct clades introduced from the Northeast region in mid-2015 (clade RJ1, n = 63/67 genomes from Rio de Janeiro) and mid-2017 (clade RJ2, n = 4/67). We detected evidence for positive selection in non-structural proteins linked with viral replication in the RJ1 clade (clade-defining: nsP4-A481D) and the RJ2 clade (nsP1-D531G). Finally, we estimate the CHIKV-ECSA's basic reproduction number (R0) to be between 1.2 to 1.6 and show that its instantaneous reproduction number (Rt) displays a strong seasonal pattern with peaks in transmission coinciding with periods of high Aedes aegypti transmission potential. Our results highlight the need for continued genomic and epidemiological surveillance of CHIKV in Brazil, particularly during periods of high ecological suitability, and show that selective pressures underline the emergence and evolution of the large urban CHIKV-ECSA outbreak in Rio de Janeiro. Author summary: Chikungunya is a mosquito-borne viral disease that has emerged as a significant public health concern in many regions worldwide. The state of Rio de Janeiro, a key economic and tourism hub in Brazil, has experienced multiple outbreaks of chikungunya in recent years, resulting in significant morbidity and economic burden. However, our understanding of the establishment and epidemiology of chikungunya in Rio de Janeiro remains limited. We conducted an analysis of chikungunya epidemiology in Rio de Janeiro, focusing on the first four years of virus circulation in the state. We estimated the magnitude of chikungunya transmission during this period, providing evidence that the trends of incidence and transmissibility can be influenced by climatic fluctuations, which impact vector abundance. Through analysis of novel genetic data, we inferred the evolutionary history of the virus, providing evidence of molecular adaptation in the lineage circulating in Rio de Janeiro. These findings highlight the need for designing effective vector control strategies to prevent and mitigate chikungunya in Rio de Janeiro and similar settings. Further research is needed to continue monitoring viral epidemiological trends and to better understand the complex interactions between climatic factors, vector dynamics, and viral evolution in shaping the transmission of this emerging disease. [ABSTRACT FROM AUTHOR]

Background and Purpose: Epoxyeicosatrienoic acids (EETs) and other epoxy fatty acids (EpFA) are lipid mediators that are rapidly inactivated by soluble epoxide hydrolase (sEH). Uncontrolled and chronic inflammatory disorders fail to sufficiently activate endogenous regulatory pathways, including the production of specialized pro‐resolving mediators (SPMs). Here, we addressed the relationship between SPMs and the EET/sEH axis and explored the effects of sEH inhibition on resolving macrophage phenotype. Experimental Approach: Mice were treated with a sEH inhibitor, EETs, or sEH inhibitor + EETs (combination) before ligature placement to induce experimental periodontitis. Using RT‐qPCR, gingival samples were used to examine SPM receptors and osteolytic and inflammatory biomarkers. Maxillary alveolar bone loss was quantified by micro‐CT and methylene blue staining. SPM levels were analysed by salivary metabolo‐lipidomics. Gingival macrophage phenotype plasticity was determined by RT‐qPCR and flow cytometry. Effects of sEH inhibition on macrophage polarization and SPM production were assessed with bone marrow‐derived macrophages (BMDMs). Key Results: Pharmacological inhibition of sEH suppressed bone resorption and the inflammatory cytokine storm in experimental periodontitis. Lipidomic analysis revealed that sEH inhibition augmented levels of LXA4, RvE1, RvE2, and 4‐HDoHE, concomitant with up‐regulation of LTB4R1, CMKLR1/ChemR23, and ALX/FPR2 SPM receptors. Notably, there is an impact on gingival macrophage plasticity was affected suggesting an inflammation resolving phenotype with sEH inhibition. In BMDMs, sEH inhibition reduced inflammatory macrophage activation, and resolving macrophages were triggered to produce SPMs. Conclusion and Implications: Pharmacological sEH inhibition increased SPM synthesis associated with resolving macrophages, suggesting a potential target to control osteolytic inflammatory disorders. [ABSTRACT FROM AUTHOR]

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