Abstract
We present the first results from the Mapping Obscuration to Reionization with ALMA (MORA) survey, the largest Atacama Large Millimeter/submillimeter Array (ALMA) blank-field contiguous ...survey to date (184 arcmin
2
) and the only at 2 mm to search for dusty star-forming galaxies (DSFGs). We use the 13 sources detected above 5
σ
to estimate the first ALMA galaxy number counts at this wavelength. These number counts are then combined with the state-of-the-art galaxy number counts at 1.2 and 3 mm and with a backward evolution model to place constraints on the evolution of the IR luminosity function and dust-obscured star formation in the past 13 billion years. Our results suggest a steep redshift evolution on the space density of DSFGs and confirm the flattening of the IR luminosity function at faint luminosities, with a slope of
. We conclude that the dust-obscured component, which peaks at
z
≈ 2–2.5, has dominated the cosmic history of star formation for the past ∼12 billion years, back to
z
∼ 4. At
z
= 5, the dust-obscured star formation is estimated to be ∼35% of the total star formation rate density and decreases to 25%–20% at
z
= 6–7, implying a minor contribution of dust-enshrouded star formation in the first billion years of the universe. With the dust-obscured star formation history constrained up to the end of the epoch of reionization, our results provide a benchmark to test galaxy formation models, to study the galaxy mass assembly history, and to understand the dust and metal enrichment of the universe at early times.
Galaxies in the early Universe that are bright at submillimetre wavelengths (submillimetre-bright galaxies) are forming stars at a rate roughly 1,000 times higher than the Milky Way. A large fraction ...of the new stars form in the central kiloparsec of the galaxy
, a region that is comparable in size to the massive, quiescent galaxies found at the peak of cosmic star-formation history
and the cores of present-day giant elliptical galaxies. The physical and kinematic properties inside these compact starburst cores are poorly understood because probing them at relevant spatial scales requires extremely high angular resolution. Here we report observations with a linear resolution of 550 parsecs of gas and dust in an unlensed, submillimetre-bright galaxy at a redshift of z = 4.3, when the Universe was less than two billion years old. We resolve the spatial and kinematic structure of the molecular gas inside the heavily dust-obscured core and show that the underlying gas disk is clumpy and rotationally supported (that is, its rotation velocity is larger than the velocity dispersion). Our analysis of the molecular gas mass per unit area suggests that the starburst disk is gravitationally unstable, which implies that the self-gravity of the gas is stronger than the differential rotation of the disk and the internal pressure due to stellar-radiation feedback. As a result of the gravitational instability in the disk, the molecular gas would be consumed by star formation on a timescale of 100 million years, which is comparable to gas depletion times in merging starburst galaxies
.
Professional phagocytes (such as macrophages) and non-professional phagocytes (such as epithelial cells) clear billions of apoptotic cells and particles on a daily basis. Although professional and ...non-professional macrophages reside in proximity in most tissues, whether they communicate with each other during cell clearance, and how this might affect inflammation, is not known. Here we show that macrophages, through the release of a soluble growth factor and microvesicles, alter the type of particles engulfed by non-professional phagocytes and influence their inflammatory response. During phagocytosis of apoptotic cells or in response to inflammation-associated cytokines, macrophages released insulin-like growth factor 1 (IGF-1). The binding of IGF-1 to its receptor on non-professional phagocytes redirected their phagocytosis, such that uptake of larger apoptotic cells was reduced whereas engulfment of microvesicles was increased. IGF-1 did not alter engulfment by macrophages. Macrophages also released microvesicles, whose uptake by epithelial cells was enhanced by IGF-1 and led to decreased inflammatory responses by epithelial cells. Consistent with these observations, deletion of IGF-1 receptor in airway epithelial cells led to exacerbated lung inflammation after allergen exposure. These genetic and functional studies reveal that IGF-1- and microvesicle-dependent communication between macrophages and epithelial cells can critically influence the magnitude of tissue inflammation in vivo.
Chatbot‐mediated learning of cardiac auscultation Cho, Kenneth; Foo, Yun M.; Dalziel, Bronwen ...
Internal medicine journal,
December 2022, 2022-12-00, 20221201, Letnik:
52, Številka:
12
Journal Article
Recenzirano
Previous research suggested cardiac auscultation is underdeveloped in physicians‐in‐training. Developing proficiency requires wide exposure to signs, practice and feedback, which may not regularly ...occur in clinical environments. Our novel pilot study using a mixed‐methods approach (n = 9) suggests chatbot‐mediated learning of cardiac auscultation is accessible and possesses unique advantages, including immediate feedback, helping in the management of cognitive overload and facilitating deliberate practice.
Lung epithelial cells can influence immune responses to airway allergens. Airway epithelial cells also undergo apoptosis after encountering environmental allergens; yet, relatively little is known ...about how these are cleared, and their effect on airway inflammation. Here we show that airway epithelial cells efficiently engulf apoptotic epithelial cells and secrete anti-inflammatory cytokines, dependent upon intracellular signalling by the small GTPase Rac1. Inducible deletion of Rac1 expression specifically in airway epithelial cells in a mouse model resulted in defective engulfment by epithelial cells and aberrant anti-inflammatory cytokine production. Intranasal priming and challenge of these mice with house dust mite extract or ovalbumin as allergens led to exacerbated inflammation, augmented Th2 cytokines and airway hyper-responsiveness, with decreased interleukin (IL)-10 in bronchial lavages. Rac1-deficient epithelial cells produced much higher IL-33 upon allergen or apoptotic cell encounter, with increased numbers of nuocyte-like cells. Administration of exogenous IL-10 'rescued' the airway inflammation phenotype in Rac1-deficient mice, with decreased IL-33. Collectively, these genetic and functional studies suggest a new role for Rac1-dependent engulfment by airway epithelial cells and in establishing the anti-inflammatory environment, and that defects in cell clearance in the airways could contribute to inflammatory responses towards common allergens.
Celotno besedilo
Dostopno za:
DOBA, IJS, IZUM, KILJ, KISLJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Dissipation is vital to any cyclic process in realistic systems. Recent research focus on nonequilibrium processes in stochastic systems has revealed a fundamental trade-off, called dissipation-time ...uncertainty relation, that entropy production rate associated with dissipation bounds the evolution pace of physical processes Phys. Rev. Lett. 125, 120604 (2020)PRLTAO0031-900710.1103/PhysRevLett.125.120604. Following the dissipative two-level model exemplified in the same Letter, we experimentally verify this fundamental trade-off in a single trapped ultracold ^{40}Ca^{+} ion using elaborately designed dissipative channels, along with a postprocessing method developed in the data analysis, to build the effective nonequilibrium stochastic evolutions for the energy transfer between two heat baths mediated by a qubit. Since the dissipation-time uncertainty relation imposes a constraint on the quantum speed regarding entropy flux, our observation provides the first experimental evidence confirming such a speed restriction from thermodynamics on quantum operations due to dissipation, which helps us further understand the role of thermodynamical characteristics played in quantum information processing.
Malignant pleural mesothelioma (MPM) is a heterogeneous cancer composed of distinct molecular and pathologic subtypes. Unfortunately, MPM is aggressive, and current therapies for advanced, ...unresectable disease remain limited to cytotoxic chemotherapy and immunotherapy. Our understanding of the genomic landscape of MPM is steadily growing, while the discovery of effective targeted therapies in MPM has advanced more slowly than in other solid tumors. Given the prevalence of alterations in tumor suppressor genes in MPM, it has been challenging to identify actionable targets. However, efforts to characterize the genetic signatures in MPM over the last decade have led to a range of novel targeted therapeutics entering early-phase clinical trials. In this review, we discuss the advancements made thus far in targeted systemic therapies in MPM and the future direction of targeted strategies in patients with advanced MPM.
Despite remarkable progress in cutaneous melanoma genomic profiling, the mutational landscape of primary mucosal melanomas (PMM) remains unclear. Forty-six PMMs underwent targeted exome sequencing of ...111 cancer-associated genes. Seventy-six somatic nonsynonymous mutations in 42 genes were observed, and recurrent mutations were noted on eight genes, including TP53 (13%), NRAS (13%), SNX31 (9%), NF1 (9%), KIT (7%) and APC (7%). Mitogen-activated protein kinase (MAPK; 37%), cell cycle (20%) and phosphatidylinositol 3-kinase (PI3K)-mTOR (15%) pathways were frequently mutated. We biologically characterized a novel ZNF767-BRAF fusion found in a vemurafenib-refractory respiratory tract PMM, from which cell line harboring ZNF767-BRAF fusion were established for further molecular analyses. In an independent data set, NFIC-BRAF fusion was identified in an oral PMM case and TMEM178B-BRAF fusion and DGKI-BRAF fusion were identified in two malignant melanomas with a low mutational burden (number of mutation per megabase, 0.8 and 4, respectively). Subsequent analyses revealed that the ZNF767-BRAF fusion protein promotes RAF dimerization and activation of the MAPK pathway. We next tested the in vitro and in vivo efficacy of vemurafenib, trametinib, BKM120 or LEE011 alone and in combination. Trametinib effectively inhibited tumor cell growth in vitro, but the combination of trametinib and BKM120 or LEE011 yielded more than additive anti-tumor effects both in vitro and in vivo in a melanoma cells harboring the BRAF fusion. In conclusion, BRAF fusions define a new molecular subset of PMM that can be targeted therapeutically by the combination of a MEK inhibitor with PI3K or cyclin-dependent kinase 4/6 inhibitors.
Leukotriene A₄ hydrolase (LTA₄H) is a proinflammatory enzyme that generates the inflammatory mediator leukotriene B₄ (LTB₄). LTA₄H also possesses aminopeptidase activity with unknown substrate and ...physiological importance; we identified the neutrophil chemoattractant prolineglycine-proline (PGP) as this physiological substrate. PGP is a biomarker for chronic obstructive pulmonary disease (COPD) and is implicated in neutrophil persistence in the lung. In acute neutrophil-driven inflammation, PGP was degraded by LTA₄H, which facilitated the resolution of inflammation. In contrast, cigarette smoke, a major risk factor for the development of COPD, selectively inhibited LTA₄H aminopeptidase activity, which led to the accumulation of PGP and neutrophils. These studies imply that therapeutic strategies inhibiting LTA₄H to prevent LTB₄ generation may not reduce neutrophil recruitment because of elevated levels of PGP.
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