This Letter reports the first results of a direct dark matter search with the DEAP-3600 single-phase liquid argon (LAr) detector. The experiment was performed 2 km underground at SNOLAB (Sudbury, ...Canada) utilizing a large target mass, with the LAr target contained in a spherical acrylic vessel of 3600 kg capacity. The LAr is viewed by an array of PMTs, which would register scintillation light produced by rare nuclear recoil signals induced by dark matter particle scattering. An analysis of 4.44 live days (fiducial exposure of 9.87 ton day) of data taken during the initial filling phase demonstrates the best electronic recoil rejection using pulse-shape discrimination in argon, with leakage <1.2×10^{-7} (90% C.L.) between 15 and 31 keV_{ee}. No candidate signal events are observed, which results in the leading limit on weakly interacting massive particle (WIMP)-nucleon spin-independent cross section on argon, <1.2×10^{-44} cm^{2} for a 100 GeV/c^{2} WIMP mass (90% C.L.).
Fusion oncogenes (FOs) are common in many cancer types and are powerful drivers of tumor development. Because their expression is exclusive to cancer cells and their elimination induces cell ...apoptosis in FO-driven cancers, FOs are attractive therapeutic targets. However, specifically targeting the resulting chimeric products is challenging. Based on CRISPR/Cas9 technology, here we devise a simple, efficient and non-patient-specific gene-editing strategy through targeting of two introns of the genes involved in the rearrangement, allowing for robust disruption of the FO specifically in cancer cells. As a proof-of-concept of its potential, we demonstrate the efficacy of intron-based targeting of transcription factors or tyrosine kinase FOs in reducing tumor burden/mortality in in vivo models. The FO targeting approach presented here might open new horizons for the selective elimination of cancer cells.
► Friction spot joining produces strong Mg AZ31–PPS-composite hybrid joints (28
MPa) ► Average process temperatures within 50–80% of the AZ31 melting point ► Thermo-mechanical processing promotes ...dynamic recrystallization in the AZ31 alloy ► Mg-composite interface is hold by mechanical and adhesive forces.
In the present study, the feasibility of the friction spot joining technique on magnesium AZ31–O/glass fiber and carbon fiber reinforced poly(phenylene sulfide) joints is addressed. The thermo-mechanical phenomena associated with the friction spot joining process promoted metallurgical and polymer physical–chemical transformations. These effects resulted in grain refinement by dynamic recrystallization and changes in local (microhardness) and global strength (lap shear). Friction spot lap joints with elevated mechanical performance (20–28
MPa) were produced without surface pre-treatment. This preliminary investigation has successfully shown that friction spot joining is an alternative technology for producing hybrid polymer–metal structures.
The Abrolhos Bank is an area of high ecological, socio-economic importance and harbour the richest and most-extensive coral reefs in the South Atlantic. Here we report the discovery of shallow ...(12–25m depth) reef complex with ten large biogenic structures, intermediate between the typical mushroom-shaped pinnacles of the northern Abrolhos Bank (17°–18° S) and the small patch reefs found on the central/southern coast of the Espírito Santo State (19°–20° S). The newly discovered reefs harbour a relatively rich and abundant reef community, with 73 fish and 14 benthic cnidarian species, including endangered and commercially important ones. We discuss on urgent needs of properly mapping and understanding the ecological functioning of this reef system. Information provided here is a baseline for future impact evaluations, particularly considering the recent worst environmental disaster of Brazil from a dam collapse in Doce river that affected the region.
Objectives
We tested the effects of a weight-loss intervention encouraging energy-reduced MedDiet and physical activity (PA) in comparison to
ad libitum
MedDiet on COVID-19 incidence in older adults.
...Design
Secondary analysis of PREDIMED-Plus, a prospective, ongoing, multicentre randomized controlled trial.
Setting
Community-dwelling, free-living participants in PREDIMED-Plus trial.
Participants
6,874 Spanish older adults (55–75 years, 49% women) with overweight/obesity and metabolic syndrome.
Intervention
Participants were randomised to Intervention (IG) or Control (CG) Group. IG received intensive behavioural intervention for weight loss with an energy-reduced MedDiet intervention and PA promotion. CG was encouraged to consume
ad libitum
MedDiet without PA recommendations.
Measurements
COVID-19 was ascertained by an independent Event Committee until December 31, 2021. COX regression models compared the effect of PREDIMED-Plus interventions on COVID-19 risk.
Results
Overall, 653 COVID-19 incident cases were documented (IG:317; CG:336) over a median (IQR) follow-up of 5.8 (1.3) years (inclusive of 4.0 (1.2) years before community transmission of COVID-19) in both groups. A significantly lowered risk of COVID-19 incidence was not evident in IG, compared to CG (fully-adjusted HR (95% CI): 0.96 (0.81,1.12)).
Conclusions
There was no evidence to show that an intensive weight-loss intervention encouraging energy-reduced MedDiet and PA significantly lowered COVID-19 risk in older adults with overweight/ obesity and metabolic syndrome in comparison to
ad libitum
MedDiet. Recommendations to improve adherence to MedDiet provided with or without lifestyle modification suggestions for weight loss may have similar effects in protecting against COVID-19 risk in older adults with high cardiovascular risks.
Aim
Intestinal dysfunction in cirrhosis patients is linked to death by bacterial infections. Currently, there is no effective therapy for this complication. This study aims to evaluate butyrate, a ...novel postbiotic, on the intestinal inflammatory response, tight junction proteins and the microbiota in the cholestasis model.
Methods and Results
Wistar rats underwent 15 days of bile duct ligation (BDL). We administered butyrate at a concentration of 1%. The BDL group did not receive treatment. The results showed that butyrate could significantly reduce pro‐inflammatory cytokines (IL‐17A, IFN‐γ, TNF‐α) in the ileum and colon while promoting IL‐10 expression in the colon. Moreover, it significantly promotes tight junction protein (cld‐1, occludin and ZO‐1) expression in the ileum. A similar effect was observed in the colon except for ZO‐1. Additionally, butyrate limited taxa diversity loss and promoted probiotic genera expansion such as Lachnospira, Prevotella and Lactobacillus. The increase in Turicibacter and Clostridiaceae distinguished the BDL group.
Conclusions
Butyrate is effective in regulating the inflammatory response, tight junction proteins and limits bacterial diversity loss.
Significance and Impact of the Study
This research reveals that butyrate could represent an interesting postbiotic metabolomic intervention for intestinal epithelium dysfunction in liver disease.
The low coverage adsorption properties of alkanes, alkenes, and aromatics of the linear, branched, and cyclic type (ca. 70 molecules) were studied using inverse pulse gas chromatography at zero ...coverage on the zirconium metal–organic framework UiO-66 and its functionalized analogues UiO-66-Me, UiO-66-NO2, UiO-66-Me2 in the temperature range 433–573 K. In our study, we determined and analyzed the adsorption enthalpy, Henry constants, and entropic factors. Preferential adsorption of bulky molecules is observed with specific adsorbate and cage size effects, yielding very specific, preferential adsorption. Remarkably high adsorption selectivity factors (up to 14) for cyclo- compared to n-alkanes were found. The presence of additional groups (methyl, nitro) on the linkers in the framework influences adsorption properties significantly, mainly by reducing the effective pore size. Whereas increased selectivity is observed for UiO-66-Me, this effect decreases again upon addition of a second methyl group, UiO-66-Me2. The latter allows for tuning confinement factors inside the pores, thus adsorption properties of the metal–organic framework. The selective adsorption results from the interaction in the smallest octahedral cage. The extreme confinement in the tetrahedral cage allows for stereoselective separation of disubstituted cycloalkanes and cis/trans alkenes. Monte Carlo simulations were performed for the unfunctionalized UiO-66 framework. First, a comparative study between the force fields Dreiding and UFF is performed with n-alkanes to obtain accurate and reproducible values. The simulations show adsorbate molecular size–adsorbent cage size effects similar to window/cage effects reported for zeolites (e.g., silicalite). Second, adsorption properties were simulated for selected cases, including stereoisomers. Careful analysis of the adsorbate’s molecular positioning in the framework confirms the experimental data. The framework’s selectivity results from adsorption in the tetrahedral cage at zero coverage. Furthermore, simulations show important contributions of entropic factors to the observed adsorption selectivity.
Rodríguez‐Lozano FJ, Bueno C, Insausti CL, Meseguer L, Ramírez MC, Blanquer M, Marín N, Martínez S, Moraleda JM. Mesenchymal stem cells derived from dental tissues. International Endodontic Journal, ...44, 800–806, 2011.
Regeneration of tissues occurs naturally due to the existence of stem cells with the capacity to self‐regenerate and differentiate; however, regenerative capacity decreases with age, and in many cases, regeneration is not sufficient to repair the damage produced by degenerative, ischaemic, inflammatory, or tumour‐based diseases. In the last decade, advances have been made in the understanding of stem cells, the genes that control the alternative fates of quiescence and differentiation, and the niches that provide specific signals that modulate cell fate decisions. Embryonic stem‐cell research is shedding light on the secrets of development. Adult stem cells (AS cells) are available from several sources. Bone marrow and connective tissue have been used in preliminary clinical trials for regenerative therapy. Recently, several types of AS cells have been isolated from teeth, including dental pulp stem cells, stem cells from human exfoliated deciduous teeth, periodontal ligament stem cells, dental follicle progenitor stem cells and stem cells from apical papilla. Preliminary data suggest that these cells have the capacity to differentiate into osteoblasts, adipocytes, chondrocytes and neural cells. If confirmed, these data would support the use of these cells, which are easily obtained from extracted teeth, in dental therapies, including in regenerative endodontics, providing a new therapeutic modality.
Cornelia de Lange Syndrome (CdLS) is a rare congenital disorder characterized by typical facial features, growth failure, limb abnormalities, and gastroesophageal dysfunction that may be caused by ...mutations in several genes that disrupt gene regulation early in development. Symptoms in individuals with CdLS suggest that the peripheral nervous system (PNS) is involved, yet there is little direct evidence. Somatic nervous system was evaluated by conventional motor and sensory nerve conduction studies and autonomic nervous system by heart rate variability, sympathetic skin response and sudomotor testing. CdLS Clinical Score and genetic studies were also obtained. Sympathetic skin response and sudomotor test were pathological in 35% and 34% of the individuals with CdLS, respectively. Nevertheless, normal values in large fiber nerve function studies. Autonomic nervous system (ANS) dysfunction is found in many individuals with Cornelia de Lange Syndrome, and could be related to premature aging.
Tuta absoluta (Meyrick; Lepidoptera: Gelechiidae) is a key pest of tomato and is quickly spreading over the world. We conducted an experiment aimed at evaluating the control capacity and risk for ...plant damage of three Neotropical mirid species, Campyloneuropsis infumatus (Carvalho; Hemiptera: Miridae), Engytatus varians (Distant; Hemiptera: Miridae) and Macrolophus basicornis (Stal; Hemiptera: Miridae) on T. absoluta infested tomato plants in large cages in an experimental greenhouse. During three successive periods of 9 wk each, we followed population development of the three mirids when exposed to T. absoluta, and of T. absoluta alone in separate cages in the greenhouse. We determined weekly the numbers of T. absoluta eggs and larvae per leaf, the number of mirid predators per leaf, the percentage of damaged leaves and fruits by T. absoluta, and the weight of fruits. Two of the mirid predators, C. infumatus and M. basicornis, successfully established on T. absoluta infested tomato plants and significantly reduced T. absoluta numbers, which ultimately resulted in an increased yield.These two mirid species hardly injured tomato plants or fruits as a result of plant feeding. Surprisingly, the species E. varians, which showed high predation rates in laboratory experiments, did not establish and reduce pest populations in any of the tests.
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