Biomorpher: interactive evolution for parametric design

Combining graph-based parametric design with metaheuristic solvers has to date focussed solely on performance based criteria and solving clearly defined objectives. In this paper, we outline a new method for combining a parametric modelling environment with an interactive Cluster-Orientated Genetic Algorithm (COGA). In addition to performance criteria, evolutionary design exploration can be guided through choice alone, with user motivation that cannot be easily defined. As well as numeric parameters forming a genotype, the evolution of whole parametric definitions is discussed through the use of genetic programming. Visualisation techniques that enable mixing small populations for interactive evolution with large populations for performance-based optimisation are discussed, with examples from both academia and industry showing a wide range of applications

The Star-forming and Ionizing Properties of Dwarf z~6-9 Galaxies in JADES: Insights on Bursty Star Formation and Ionized Bubble Growth

Reionization is thought to be driven by faint star-forming galaxies, but characterizing this population in detail has long remained very challenging. Here we utilize deep nine-band NIRCam imaging from JADES to study the star-forming and ionizing properties of 756 $z\sim6-9$ galaxies, including hundreds of very UV-faint objects ($M_\mathrm{UV}>-18$). The faintest ($m\sim30$) galaxies in our sample typically have stellar masses of $M_\ast\sim(1-3)\times10^7$ $M_\odot$ and young light-weighted ages ($\sim$50 Myr), though some show strong Balmer breaks implying much older ages ($\sim$500 Myr). We find no evidence for extremely massive galaxies ($>3\times10^{10}$ $M_\odot$) in our sample. We infer a strong (factor $>$2) decline in the typical [OIII]$+$H$\beta$ EWs towards very faint $z\sim6-9$ galaxies, yet a weak UV luminosity dependence on the H$\alpha$ EWs at $z\sim6$. We demonstrate that these EW trends can be explained if fainter galaxies have systematically lower metallicities as well as more recently-declining star formation histories relative to the most UV-luminous galaxies in our sample. Our data provide evidence that the brightest galaxies are frequently experiencing a recent strong upturn in SFR. We also discuss how the EW trends may be influenced by a strong correlation between $M_\mathrm{UV}$ and Lyman continuum escape fraction. This alternative explanation has dramatically different implications for the contribution of galaxies along the luminosity function to cosmic reionization, highlighting the need for deep spectroscopic follow-up. Finally, we quantify the photometric overdensities around two $z>7$ strong Ly$\alpha$ emitters in the JADES footprint. One Ly$\alpha$ emitter lies close to a strong photometric overdensity while the other shows no significant nearby overdensity, perhaps implying that not all strong $z>7$ Ly$\alpha$ emitters reside in large ionized bubbles.Comment: 29 pages, 16 figures. Submitted to MNRAS. Comments welcom

JADES Initial Data Release for the Hubble Ultra Deep Field: Revealing the Faint Infrared Sky with Deep JWST NIRCam Imaging

JWST has revolutionized the field of extragalactic astronomy with its sensitive and high-resolution infrared view of the distant universe. Adding to the new legacy of JWST observations, we present the first NIRCam imaging data release from the JWST Advanced Deep Extragalactic Survey (JADES) providing 9 filters of infrared imaging of $\sim$25 arcmin$^2$ covering the Hubble Ultra Deep Field and portions of Great Observatories Origins Deep Survey (GOODS) South. Utilizing 87 on-sky dual-filter hours of exposure time, these images reveal the deepest ever near-infrared view of this iconic field. We supply carefully constructed 9-band mosaics of the JADES bands, as well as matching reductions of 5 additional bands from the JWST Extragalactic Medium-band Survey (JEMS). Combining with existing HST imaging, we provide 23-band space-based photometric catalogs and photometric redshifts for $\approx47,500$ sources. To promote broad engagement with the JADES survey, we have created an interactive {\tt FitsMap} website to provide an interface for professional researchers and the public to experience these JWST datasets. Combined with the first JADES NIRSpec data release, these public JADES imaging and spectroscopic datasets provide a new foundation for discoveries of the infrared universe by the worldwide scientific community.Comment: Several figures were modified to use better line styles. A brief comparison to IRAC Channel 1 photometry was added along with a few other clarifications. Paper has been accepted for publication in ApJ

JADES Initial Data Release for the Hubble Ultra Deep Field: Revealing the Faint Infrared Sky with Deep JWST NIRCam Imaging

© 2023. The Author(s). Published by the American Astronomical Society. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY), https://creativecommons.org/licenses/by/4.0/JWST has revolutionized the field of extragalactic astronomy with its sensitive and high-resolution infrared view of the distant Universe. Adding to the new legacy of JWST observations, we present the first NIRCam imaging data release from the JWST Advanced Deep Extragalactic Survey (JADES), providing nine filters of infrared imaging of ∼25 arcmin2 covering the Hubble Ultra Deep Field and portions of Great Observatories Origins Deep Survey South. Utilizing 87 on-sky dual-filter hours of exposure time, these images reveal the deepest ever near-infrared view of this iconic field. We supply carefully constructed nine-band mosaics of the JADES bands, as well as matching reductions of five additional bands from the JWST Extragalactic Medium-band Survey. Combining with existing Hubble Space Telescope imaging, we provide 23-band space-based photometric catalogs and photometric redshifts for ≈47,500 sources. To promote broad engagement with JADES, we have created an interactive FitsMap website to provide an interface for professional researchers and the public to experience these JWST data sets. Combined with the first JADES NIRSpec data release, these public JADES imaging and spectroscopic data sets provide a new foundation for discoveries of the infrared Universe by the worldwide scientific community.Peer reviewe

First genotype-phenotype study in TBX4 syndrome : gain-of-function mutations causative for lung disease

Rationale: Despite the increased recognition of TBX4-associated pulmonary arterial hypertension (PAH), genotype-phenotype associations are lacking and may provide important insights. Methods: We assembled a multi-center cohort of 137 patients harboring monoallelic TBX4 variants and assessed the pathogenicity of missense variation (n = 42) using a novel luciferase reporter assay containing T-BOX binding motifs. We sought genotype-phenotype correlations and undertook a comparative analysis with PAH patients with BMPR2 causal variants (n = 162) or no identified variants in PAH-associated genes (n = 741) genotyped via the NIHR BioResource - Rare Diseases (NBR). Results: Functional assessment of TBX4 missense variants led to the novel finding of gain-of-function effects associated with older age at diagnosis of lung disease compared to loss-of-function (p = 0.038). Variants located in the T-BOX and nuclear localization domains were associated with earlier presentation (p = 0.005) and increased incidence of interstitial lung disease (p = 0.003). Event-free survival (death or transplantation) was shorter in the T-BOX group (p = 0.022) although age had a significant effect in the hazard model (p = 0.0461). Carriers of TBX4 variants were diagnosed at a younger age (p < 0.001) and had worse baseline lung function (FEV1, FVC) (p = 0.009) compared to the BMPR2 and no identified causal variant groups. Conclusions: We demonstrated that TBX4 syndrome is not strictly the result of haploinsufficiency but can also be caused by gain-of-function. The pleiotropic effects of TBX4 in lung disease may be in part explained by the differential effect of pathogenic mutations located in critical protein domains

Evidence for sex-dependent anabolic response to androgenic steroids mediated by muscle glucocorticoid receptors in the rat.

The muscle anabolic/anti-catabolic activity of the androgenic steroids testosterone and trenbolone was studied in rats to investigate whether such steroids act as agonists via muscle androgen receptors, or as antagonists that oppose the catabolic effects of endogenous glucocorticoids via their interaction with muscle glucocorticoid receptors. For comparison, the effects of the potent glucocorticoid antagonist RU486 were also examined. The parameters measured included growth rate, muscle weight, serum growth hormone and corticosterone levels, and receptor binding parameters in muscle cytosol. Females responded better than males to anabolic treatment with the androgenic steroids. Ovariectomy or adrenalectomy abolished this response. Neither the sex difference nor the requirement for ovaries or adrenals could be explained in terms of muscle receptor parameters or serum growth hormone levels. The muscle anabolic activity of androgenic steroids was restored when castrated males were treated with oestradiol and when adrenalectomized females were treated with corticosterone. RU486 also prevented the catabolic/anti-anabolic activity of exogenous corticosterone in adrenalectomized rats. Testosterone and RU486 behaved as anti-glucocorticoids in vivo since they inhibited glucocorticoid-induced liver tyrosine aminotransferase activity. The results suggest that anabolic steroids can act via muscle glucocorticoid receptors, thereby antagonizing the catabolic activity of endogenous glucocorticoids, rather than via muscle androgen receptors

Properties of galactosyltransferase from human milk fat globules

SCOPUS: ar.jinfo:eu-repo/semantics/publishe

Altered surfactant homeostasis and recurrent respiratory failure secondary to TTF-1 nuclear targeting defect.

BackgroundMutations of genes affecting surfactant homeostasis, such as SFTPB, SFTPC and ABCA3, lead to diffuse lung disease in neonates and children. Haploinsufficiency of NKX2.1, the gene encoding the thyroid transcription factor-1 (TTF-1)--critical for lung, thyroid and central nervous system morphogenesis and function--causes a rare form of progressive respiratory failure designated brain-lung-thyroid syndrome. Molecular mechanisms involved in this syndrome are heterogeneous and poorly explored. We report a novel TTF-1 molecular defect causing recurrent respiratory failure episodes in an infant.MethodsThe subject was an infant with severe neonatal respiratory distress syndrome followed by recurrent respiratory failure episodes, hypopituitarism and neurological abnormalities. Lung histology and ultrastructure were assessed by surgical biopsy. Surfactant-related genes were studied by direct genomic DNA sequencing and array chromatine genomic hybridization (aCGH). Surfactant protein expression in lung tissue was analyzed by confocal immunofluorescence microscopy. For kinetics studies, surfactant protein B and disaturated phosphatidylcholine (DSPC) were isolated from serial tracheal aspirates after intravenous administration of stable isotope-labeled (2)H(2)O and (13)C-leucine; fractional synthetic rate was derived from gas chromatography/mass spectrometry (2)H and (13)C enrichment curves. Six intubated infants with no primary lung disease were used as controls.ResultsLung biopsy showed desquamative interstitial pneumonitis and lamellar body abnormalities suggestive of genetic surfactant deficiency. Genetic studies identified a heterozygous ABCA3 mutation, L941P, previously unreported. No SFTPB, SFTPC or NKX2.1 mutations or deletions were found. However, immunofluorescence studies showed TTF-1 prevalently expressed in type II cell cytoplasm instead of nucleus, indicating defective nuclear targeting. This pattern has not been reported in human and was not found in two healthy controls and in five ABCA3 mutation carriers. Kinetic studies demonstrated a marked reduction of SP-B synthesis (43.2 vs. 76.5 ± 24.8%/day); conversely, DSPC synthesis was higher (12.4 vs. 6.3 ± 0.5%/day) compared to controls, although there was a marked reduction of DSPC content in tracheal aspirates (29.8 vs. 56.1 ± 12.4% of total phospholipid content).ConclusionDefective TTF-1 signaling may result in profound surfactant homeostasis disruption and neonatal/pediatric diffuse lung disease. Heterozygous ABCA3 missense mutations may act as disease modifiers in other genetic surfactant defects