GOODS-ALMA 2.0: Last gigayear star formation histories of the so-called starbursts within the main sequence

Recently, a population of compact main sequence (MS) galaxies exhibiting starburst-like properties have been identified in the GOODS-ALMA blind survey at 1.1mm. Several evolution scenarios were proposed to explain their particular physical properties (e.g., compact size, low gas content, short depletion time). In this work, we aim at studying the star formation history (SFH) of the GOODS-ALMA galaxies to understand if the so-called ``starburst (SB) in the MS'' galaxies exhibit a different star formation activity over the last Gyr compared to MS galaxies that could explain their specificity. We use the CIGALE SED modelling code to which we add non-parametric SFHs. To compare quantitatively the recent SFH of the galaxies, we define a parameter, the star formation rate (SFR) gradient that provides the angle showing the direction that a galaxy has followed in the SFR vs stellar mass plane over a given period. We show that ``SB in the MS'' have positive or weak negative gradients over the last 100, 300, and 1000 Myr, at odds with a scenario where these galaxies would be transitioning from the SB region at the end of a strong starburst phase. Normal GOODS-ALMA galaxies and ``SB in the MS'' have the same SFR gradients distributions meaning that they have similar recent SFH, despite their different properties (compactness, low depletion time). The ``SBs in the MS'' manage to maintain a star-formation activity allowing them to stay within the MS. This points toward a diversity of galaxies within a complex MS.Comment: Submitted to A&

Synthesis of Nitrogenated Heterocycles by Asymmetric Transfer Hydrogenation of N-(tert-Butylsulfinyl)haloimines

Highly optically enriched, protected, nitrogenated heterocycles with different ring sizes have been synthesized by a very efficient methodology consisting of the asymmetric transfer hydrogenation of N-(tert-butylsulfinyl)haloimines followed by treatment with a base to promote an intramolecular nucleophilic substitution process. N-Protected aziridines, pyrrolidines, piperidines, and azepanes bearing aromatic, heteroaromatic, and aliphatic substituents have been obtained in very high yields and diastereomeric ratios up to >99:1. The free heterocycles can be easily obtained by a simple and mild desulfinylation procedure. Both enantiomers of the free heterocycles can be prepared with the same good results by changing the absolute configuration of the sulfur atom of the sulfinyl group.This work was generously supported by the Spanish Ministerio de Ciencia e Innovación (MICINN; grant no. CONSOLIDER INGENIO 2010, CSD2007-00006, CTQ2007-65218 and CTQ2011-24151) and the Generalitat Valenciana (PROMETEO/2009/039 and FEDER). O.P. thanks the Spanish Ministerio de Educación for a predoctoral fellowship (grant no. AP-2008-00989)

Malformaciones venosas orofaciales de bajo flujo: esclerosis endoluminal con láser de diodo

ResumenIntroducciónLas anomalías vasculares son procesos frecuentes que se localizan en más del 50% de los casos en la región de la cabeza y el cuello. Las técnicas clásicas de tratamiento, tales como la cirugía y la esclerosis química, han dado paso a modernas técnicas menos invasivas, tales como el láser Nd:YAG. Por otra parte, se ha utilizado con éxito el láser de diodo (980 nm) para el tratamiento de varices mediante esclerosis endoluminal. Nuestra propuesta es la utilización del láser de diodo (λ 980 nm) para provocar una esclerosis por fotocoagulación intralesional de las malformaciones venosas de bajo flujo dada la capacidad de este láser de ser transmitido por fibra óptica.ObjetivoExponer nuestros resultados en el tratamiento de malformaciones venosas de bajo flujo (MVBF) orofaciales mediante la terapéutica de esclerosis endoluminal con láser de diodo.Material y métodosRevisamos 84 pacientes que presentaban MVBF orofaciales tratados con láser de diodo. Describimos la técnica de realización y se muestran los resultados postoperatorios a corto plazo.ResultadosTras un periodo de seguimiento no inferior a 12 meses se constató curación en el 95,24% aplicando una o dos sesiones y solamente en 4 casos se objetivó recidiva. Concluimos que la técnica de esclerosis endoluminal con láser de diodo de MVBF en el área orofacial se constituye como una nueva técnica de tratamiento, mínimamente invasiva, ambulatoria, y que permite la resolución de los casos sin tener que recurrir a cirugías más agresivas y con excelentes resultados funcionales y estéticos.AbstractBackgroundVascular anomalies are common processes that involve the head and neck region in more than 50% of the cases. Traditional treatment options such as surgery and chemical sclerosis have given way to modern less-invasive techniques, including Nd:YAG laser treatment. On the other hand, 980 nm laser diode has been successfully used for the endovenous sclerosis of varicose veins. Our proposal is the usage of diode laser (λ = 980 nm) to induce the sclerosis of low-flow venous malformations by intralesional photocoagulation, given this laser's ability to deliver the beam via a fiber optic cable.ObjectiveTo report our results in the treatment of orofacial low-flow venous malformations (LFVM) with diode laser endovenous sclerosis (DLES).Material and methods: The clinical records from 84 patients presenting with orofacial LFVM treated with DLES were collected. The technique used and short-term postoperative results were revised.ResultsAfter a follow-up period of at least 12 months after one or two DLES sessions, healing was observed in 95.24% of the cases. Only 4 cases showed relapse.ConclusionsThe DLES technique is a new therapeutic option for the treatment of orofacial LFVM, is minimally-invasive, allows an outpatient setting and achieves excellent functional and esthetic results avoiding more aggressive procedures

Tissue remodelling and increased DNA damage in patients with incompetent valves in chronic venous insufficiency

Chronic venous insufficiency (CVI), in which blood return to the heart is impaired, is a prevalent condition worldwide. Valve incompetence is a complication of CVI that results in blood reflux, thereby aggravating venous hypertension. While CVI has a complex course and is known to produce alterations in the vein wall, the underlying pathological mechanisms remain unclear. This study examined the presence of DNA damage, pro-inflammatory cytokines and extracellular matrix remodelling in CVI-related valve incompetence. One hundred and ten patients with CVI were reviewed and divided into four groups according to age (<50 and ≥50 years) and a clinical diagnosis of venous reflux indicating venous system valve incompetence (R) (n = 81) or no reflux (NR) (n = 29). In vein specimens (greater saphenous vein) from each group, PARP, IL-17, COL-I, COL-III, MMP-2 and TIMP-2 expression levels were determined by RT-qPCR and immunohistochemistry. The younger patients with valve incompetence showed significantly higher PARP, IL-17, COL-I, COL-III, MMP-2 and reduced TIMP-2 expression levels and a higher COL-I/III ratio. Young CVI patients with venous reflux suffer chronic DNA damage, with consequences at both the local tissue and systemic levels, possibly associated with ageing.This study (FIS-PI18/00912) was supported by the Instituto de Salud Carlos III (Plan Estatal de I + D+i 2013-2016) and co-financed by the European Development Regional Fund “A way to achieve Europe” (ERDF) and B2017/BMD-3804 MITIC-CM

In pursuit of giants: I. The evolution of the dust-to-stellar mass ratio in distant dusty galaxies

The dust-to-stellar mass ratio (Mdust/M?) is a crucial, albeit poorly constrained, parameter for improving our understanding of the complex physical processes involved in the production of dust, metals, and stars in galaxy evolution. In this work, we explore trends of Mdust/M? with dierent physical parameters and using observations of 300 massive dusty star-forming galaxies detected with ALMA up to z 5. Additionally, we interpret our findings with dierent models of dusty galaxy formation. We find that Mdust/M? evolves with redshift, stellar mass, specific star formation rates, and integrated dust size, but that evolution is dierent for mainsequence galaxies than it is for starburst galaxies. In both galaxy populations, Mdust/M? increases until z 2, followed by a roughly flat trend towards higher redshifts, suggesting ecient dust growth in the distant universe. We confirm that the inverse relation between Mdust/M? and M? holds up to z 5 and can be interpreted as an evolutionary transition from early to late starburst phases. We demonstrate that the Mdust/M? in starbursts reflects the increase in molecular gas fraction with redshift and attains the highest values for sources with the most compact dusty star formation. State-of-the-art cosmological simulations that include self-consistent dust growth have the capacity to broadly reproduce the evolution of Mdust/M? in main-sequence galaxies, but underestimating it in starbursts. The latter is found to be linked to lower gas-phase metallicities and longer dust-growth timescales relative to observations. The results of phenomenological models based on the main-sequence and starburst dichotomy as well as analytical models that include recipes for rapid metal enrichment are consistent with our observations. Therefore, our results strongly suggest that high Mdust/M? is due to rapid dust grain growth in the metal-enriched interstellar medium. This work highlights the multi-fold benefits of using Mdust/M? as a diagnostic tool for: (1) disentangling main-sequence and starburst galaxies up to z 5; (2) probing the evolutionary phase of massive objects; and (3) refining the treatment of the dust life cycle in simulations

Simvastatin inhibits TLR8 signaling in primary human monocytes and spontaneous TNF production from rheumatoid synovial membrane cultures

Simvastatin has been shown to have anti-inflammatory effects that are independent of its serum cholesterol lowering action, but the mechanisms by which these anti-inflammatory effects are mediated have not been elucidated. To explore the mechanism involved, the effect of simvastatin on Toll-like receptor (TLR) signalling in primary human monocytes was investigated. A short pre-treatment with simvastatin dose-dependently inhibited the production of tumor necrosis factor-α (TNF) in response to TLR8 (but not TLRs 2, 4, or 5) activation. Statins are known inhibitors of the cholesterol biosynthetic pathway, but intriguingly TLR8 inhibition could not be reversed by addition of mevalonate or geranylgeranyl pyrophosphate; downstream products of cholesterol biosynthesis. TLR8 signalling was examined in HEK 293 cells stably expressing TLR8, where simvastatin inhibited IKKα/β phosphorylation and subsequent NF-κB activation without affecting the pathway to AP-1. Since simvastatin has been reported to have anti-inflammatory effects in RA patients and TLR8 signalling contributes to TNF production in human RA synovial tissue in culture, simvastatin was tested in these cultures. Simvastatin significantly inhibited the spontaneous release of TNF in this model which was not reversed by mevalonate. Together, these results demonstrate a hitherto unrecognized mechanism of simvastatin inhibition of TLR8 signalling that may in part explain its beneficial anti-inflammatory effects

UVB-Induced Tumor Heterogeneity Diminishes Immune Response in Melanoma

Although clonal neo-antigen burden is associated with improved response to immune therapy, the functional basis for this remains unclear. Here we study this question in a novel controlled mouse melanoma model that enables us to explore the effects of intra-tumor heterogeneity (ITH) on tumor aggressiveness and immunity independent of tumor mutational burden. Induction of UVB-derived mutations yields highly aggressive tumors with decreased anti-tumor activity. However, single-cell-derived tumors with reduced ITH are swiftly rejected. Their rejection is accompanied by increased T cell reactivity and a less suppressive microenvironment. Using phylogenetic analyses and mixing experiments of single-cell clones, we dissect two characteristics of ITH: the number of clones forming the tumor and their clonal diversity. Our analysis of melanoma patient tumor data recapitulates our results in terms of overall survival and response to immune checkpoint therapy. These findings highlight the importance of clonal mutations in robust immune surveillance and the need to quantify patient ITH to determine the response to checkpoint blockade

Tecnologias sociais: as organizações não governamentais no enfrentamento das mudanças climáticas e na promoção de desenvolvimento humano

De acordo com o quarto relatório do Intergovernmental Panel on Climate Change (IPCC), as regiões semiáridas do mundo estarão entre as mais afetadas pelos impactos das mudanças climáticas globais. Estudos realizados pelo Ministério do Meio Ambiente (MMA), em 2007, confirmam que, no Nordeste brasileiro, não apenas choverá menos e mais irregularmente, mas, também, haverá mais secas, devido ao aquecimento da temperatura. Diante dos diversos impactos sociais, ambientais e econômicos possíveis nesses cenários, é de fundamental importância a verificação de alternativas sustentáveis para o semiárido brasileiro. Este artigo tem por objetivo avaliar o potencial de algumas das tecnologias sociais (TS) de convivência com o semiárido, desenvolvidas por diversas organizações, para a mitigação das mudanças climáticas e a promoção de desenvolvimento humano. Constata-se que as TS tem grande potencial para auxiliar na mitigação e na adaptação das mudanças climáticas, ao mesmo tempo que promovem melhorias na qualidade de vida das localidades onde estão sendo desenvolvidas

GOODS-ALMA: The slow downfall of star formation in z = 2–3 massive galaxies

We investigate the properties of a sample of 35 galaxies, detected with the Atacama Large Millimeter/Submillimeter Array (ALMA) at 1.1 mm in the GOODS-ALMA field (area of 69 arcmin2, resolution = 0.60″, rms ≃ 0.18 mJy beam−1). Using the ultraviolet-to-radio deep multiwavelength coverage of the GOODS–South field, we fit the spectral energy distributions of these galaxies to derive their key physical properties. The galaxies detected by ALMA are among the most massive at z = 2−4 (M⋆, med = 8.5 × 1010 M⊙) and they are either starburst or located in the upper part of the galaxy star-forming main sequence. A significant portion of our galaxy population (∼40%), located at z ∼ 2.5 − 3, exhibits abnormally low gas fractions. The sizes of these galaxies, measured with ALMA, are compatible with the trend between the rest-frame 5000 Å size and stellar mass observed for z ∼ 2 elliptical galaxies, suggesting that they are building compact bulges. We show that there is a strong link between star formation surface density (at 1.1 mm) and gas depletion time: The more compact a galaxy’s star-forming region is, the shorter its lifetime will be (without gas replenishment). The identified compact sources associated with relatively short depletion timescales (∼100 Myr) are the ideal candidates to be the progenitors of compact elliptical galaxies at z ∼ 2