ABSTRACT
We include a fully coupled treatment of metal and dust enrichment into the Delphi semi-analytic model of galaxy formation to explain the dust content of 13 Lyman break galaxies (LBGs) ...detected by the Atacama Large millimetre Array (ALMA) REBELS Large Program at z ≃ 7. We find that the galaxy dust mass, Md, is regulated by the combination of Type II supernova dust production, astration, shock destruction, and ejection in outflows; grain growth (with a standard time-scale τ0 = 30 Myr) plays a negligible role. The model predicts a dust-to-stellar mass ratio of $\sim 0.07\!-\!0.1{{\ \rm per\ cent}}$ and a UV-to-total star formation rate relation such that log(ψUV) = −0.05 log(ψ)2 + 0.86 log(ψ) − 0.05 (implying that 55–80 per cent of the star formation is obscured) for REBELS galaxies with stellar mass $M_* = 10^{9}\!-\!10^{10} \rm M_\odot$. This relation reconciles the intrinsic UV luminosity of LBGs with their observed luminosity function at z = 7. However, 2 out of the 13 systems show dust-to-stellar mass ratios ($\sim 0.94\!-\!1.1{{\ \rm per\ cent}}$) that are up to 18 times larger than expected from the fiducial relation. Due to the physical coupling between dust and metal enrichment, even decreasing τ0 to very low values (0.3 Myr) only increases the dust-to-stellar mass ratio by a factor of ∼2. Given that grain growth is not a viable explanation for such high observed ratios of the dust-to-stellar mass, we propose alternative solutions.
Coxiella burnetii is a highly infectious, Gram-negative, obligate intracellular bacterium and the causative agent of human Q fever. The Coxiella Containing Vacuole (CCV) is a modified phagolysosome ...that forms through fusion with host endosomes and lysosomes. While an initial acidic pH < 4.7 is essential to activate Coxiella metabolism, the mature, growth-permissive CCV has a luminal pH of ~5.2 that remains stable throughout infection. Inducing CCV acidification to a lysosomal pH (~4.7) causes Coxiella degradation, suggesting that Coxiella regulates CCV pH. Supporting this hypothesis, Coxiella blocks host lysosomal biogenesis, leading to fewer host lysosomes available to fuse with the CCV. Host cell lysosome biogenesis is primarily controlled by the transcription factor EB (TFEB), which binds Coordinated Lysosomal Expression And Regulation (CLEAR) motifs upstream of genes involved in lysosomal biogenesis and function. TFEB is a member of the microphthalmia/transcription factor E (MiT/TFE) protein family, which also includes MITF, TFE3, and TFEC. This study examines the roles of MiT/TFE proteins during Coxiella infection. We found that in cells lacking TFEB, both Coxiella growth and CCV size increase. Conversely, TFEB overexpression or expression in the absence of other family members leads to significantly less bacterial growth and smaller CCVs. TFE3 and MITF do not appear to play a significant role during Coxiella infection. Surprisingly, we found that Coxiella actively blocks TFEB nuclear translocation in a Type IV Secretion System-dependent manner, thus decreasing lysosomal biogenesis. Together, these results suggest that Coxiella inhibits TFEB nuclear translocation to limit lysosomal biogenesis, thus avoiding further CCV acidification through CCV-lysosomal fusion.IMPORTANCEThe obligate intracellular bacterial pathogen Coxiella burnetii causes the zoonotic disease Q fever, which is characterized by a debilitating flu-like illness in acute cases and life-threatening endocarditis in patients with chronic disease. While Coxiella survives in a unique lysosome-like vacuole called the Coxiella Containing Vacuole (CCV), the bacterium inhibits lysosome biogenesis as a mechanism to avoid increased CCV acidification. Our results establish that transcription factor EB (TFEB), a member of the microphthalmia/transcription factor E (MiT/TFE) family of transcription factors that regulate lysosomal gene expression, restricts Coxiella infection. Surprisingly, Coxiella blocks TFEB translocation from the cytoplasm to the nucleus, thus downregulating the expression of lysosomal genes. These findings reveal a novel bacterial mechanism to regulate lysosomal biogenesis.
A new comprehensive data collection by Damboldt and Suessmann (2012a) with monthly foF2 and M(3000)F2 median values is an excellent basis for the derivation of long-term trends in the ionospheric F2 ...region. Ionospheric trends have been derived only for stations with data series of at least 22 years (124 stations with foF2 data and 113 stations with M(3000)F2 data) using a twofold regression analysis depending on solar and geomagnetic activity. Three main results have been derived: Firstly, it could be shown that the solar 10.7 cm radio flux F10.7 is a better index for the description of the solar activity than the relative solar sunspot number R as well as the solar EUV proxy E10.7. Secondly, the global mean foF2 and hmF2 trends derived for the interval between 1948 and 2006 are in surprisingly good agreement with model calculations of an increasing atmospheric greenhouse effect (Rishbeth and Roble, 1992). Thirdly, during the years 2007 until 2009, the hmF2 values and to a smaller amount the foF2 values strongly decrease. The reason for this effect is a reduction of the thermospheric density and ionization due to a markedly reduced solar EUV irradiation and extremely small geomagnetic activity during the solar cycle 23/24 minimum.
Ground based ionosonde measurements are the most essential source of information about long-term variations in the ionospheric E and F1 regions. Data of such observations have been derived at many ...different ionospheric stations all over the world some for more than 50 years. The standard parameters foE, h'E, and foF1 are used for trend analyses in this paper. Two main problems have to be considered in these analyses. Firstly, the data series have to be homogeneous, i.e. the observations should not be disturbed by artificial steps due to technical reasons or changes in the evaluation algorithm. Secondly, the strong solar and geomagnetic influences upon the ionospheric data have carefully to be removed by an appropriate regression analysis. Otherwise the small trends in the different ionospheric parameters cannot be detected. The trends derived at individual stations differ markedly, however their dependence on geographic or geomagnetic latitude is only small. Nevertheless, the mean global trends estimated from the trends at the different stations show some general behaviour (positive trends in foE and foF1, negative trend in h'E) which can at least qualitatively be explained by an increasing atmospheric greenhouse effect (increase of CO2 content and other greenhouse gases) and decreasing ozone values. The positive foE trend is also in qualitative agreement with rocket mass spectrometer observations of ion densities in the E region. First indications could be found that the changing ozone trend at mid-latitudes (before about 1979, between 1979 until 1995, and after about 1995) modifies the estimated mean foE trend.
Onsite wastewater treatment systems are common in rural and semi-rural areas around the world; in the US, about 25-30% of households are served by a septic (onsite) wastewater treatment system, and ...many property owners also operate their own domestic well nearby. Site-specific conditions and local groundwater flow are often ignored when installing septic systems and wells. In areas with small lots (thus high spatial septic system densities), shallow domestic wells are prone to contamination by septic system leachate. Mass balance approaches have been used to determine a maximum septic system density that would prevent contamination of groundwater resources. In this study, a source area model based on detailed groundwater flow and transport modeling is applied for a stochastic analysis of domestic well contamination by septic leachate. Specifically, we determine the probability that a source area overlaps with a septic system drainfield as a function of aquifer properties, septic system density and drainfield size. We show that high spatial septic system density poses a high probability of pumping septic system leachate. The hydraulic conductivity of the aquifer has a strong influence on the intersection probability. We find that mass balance calculations applied on a regional scale underestimate the contamination risk of individual drinking water wells by septic systems. This is particularly relevant for contaminants released at high concentrations, for substances that experience limited attenuation, and those that are harmful even at low concentrations (e.g., pathogens).
Purpose
The importance of follow-up (FU) for midterm weight loss (WL) after bariatric surgery is controversial. Compliance to this FU remains challenging. Several risk factors for loss to FU (LtFU) ...have been mentioned. The aim was therefore to evaluate the association between WL and LtFU 3 to 5 years postoperatively and to identify risk factors for LtFU.
Materials and Methods
A single-center cross-sectional study in the Netherlands. Between June and October 2018, patients scheduled for a 3-, 4-, or 5-year FU appointment were included into two groups: compliant (to their scheduled appointment and overall maximally 1 missed appointment) and non-compliant (missed the scheduled appointment and at least 1 overall). Baseline, surgical, and FU characteristics were collected and a questionnaire concerning socio-economic factors.
Results
In total, 217 patients in the compliant group and 181 in the non-compliant group were included with a median body mass index at baseline of 42.0 and 42.9 respectively. Eighty-eight percent underwent a laparoscopic Roux-en-Y gastric bypass. The median percentage total weight loss for the compliant and non-compliant groups was 30.7% versus 28.9% at 3, 29.3% versus 30.2% at 4, and 29.6% versus 29.9% at 5 years respectively, all
p
>0.05. Age, persistent comorbidities and vitamin deficiencies, a yearly salary <20,000 euro, no health insurance coverage, and not understanding the importance of FU were risk factors for LtFU.
Conclusion
Three to 5 years postoperatively, there is no association between LtFU and WL. The compliant group demonstrated more comorbidities and vitamin deficiencies. Younger age, not understanding the importance of FU, and financial challenges were risk factors for LtFU.
Graphical abstract
Compact high-effectiveness counter-flow heat exchangers (CFHEX) are an essential building block of remote cooling systems and Reverse Turbo-Brayton coolers. This technology enables a wide variety of ...on-ground and space applications, including the cooling of infrared detectors, cryogenic chains of quantum computers and ultra-sensitive superconducting SQUID sensors. A mesh-based CFHEX design was previously proposed for such applications and demonstrated a great potential to meet the high effectiveness and compactness needs 1. This paper presents a novel improved mesh-based CFHEX concept with a “transparent” inner wall and outlines the methods used for its manufacturing. Two of such CFHEXs are constructed and integrated in a technology demonstrator of a remote cooling system. Their performance is tested in the ▪ temperature, 1bar–5bar pressure and 50mg/s–250mg/s helium mass flow rate ranges. An effectiveness of ▪ (NTU=39–124) has been experimentally achieved with a pressure drop of less than 10mbar per stream at the nominal operating conditions of the system. The experimental effectiveness and pressure drop results are analysed and compared to numerical predictions. The implications of the achieved high effectiveness on the final performance of the designed remote cooling system are also discussed.
•Novel transparent-wall heat exchanger (HEX) design based on woven metal mesh reaches a remarkably high effectiveness.•Developed additive manufacturing method allows to fabricate mechanically sound mesh-based high-effectiveness cryogenic HEXs.•Proposed friction factor models for different woven mesh enable accurate HEX pressure drop predictions in various conditions.•Remote cooling systems based on novel HEXs have a great potential to reduce disturbances transported to the cooled object.
Summary
Carbamylation is a post‐translational modification that can be detected on a range of proteins, including immunoglobulin (Ig)G, in several clinical conditions. Carbamylated IgG (ca‐IgG) was ...reported to lose its capacity to trigger complement activation, but the mechanism remains unclear. Because C1q binds with high affinity to hexameric IgG, we analyzed whether carbamylation of IgG affects binding of C1q, hexamerization and complement‐dependent cytotoxicity (CDC). Synovial tissues of rheumatoid arthritis (RA) patients were analyzed for the presence of ca‐IgG in vivo. Synovial tissues from RA patients were analyzed for the presence of ca‐IgG using mass spectrometry (MS). Monomeric or hexameric antibodies were carbamylated in vitro and quality in solution was controlled. The capacity of ca‐IgG to activate complement was analyzed in enzyme‐linked immunosorbent (ELISAs) and cellular CDC assays. Using MS, we identified ca‐IgG to be present in the joints of RA patients. Using in vitro carbamylated antibodies, we observed that ca‐IgG lost its capacity to activate complement in both solid‐phase and CDC assays. Mixing ca‐IgG with non‐modified IgG did not result in effective inhibition of complement activation by ca‐IgG. Carbamylation of both monomeric IgG and preformed hexameric IgG greatly impaired the capacity to trigger complement activation. Furthermore, upon carbamylation, the preformed hexameric IgG dissociated into monomeric IgG in solution, indicating that carbamylation influences both hexamerization and C1q binding. In conclusion, ca‐IgG can be detected in vivo and has a strongly reduced capacity to activate complement which is, in part, mediated through a reduced ability to form hexamers.
Carbamylation of both monomeric IgG and pre‐formed hexameric IgG greatly impaired the capacity to trigger complement activation. Upon carbamylation the pre‐formed hexameric IgG, dissociated into monomeric IgG in solution. Indicating that carbamylation does not only influence C1q binding, but also the ability to form hexamers.
Assigning relative importance of spawning and nursery habitats for threatened and endangered teleosts, such as those seen in the Gulf of Mexico (GoM), relies on the proper identification of the early ...life‐history stages of the species of concern. Here, sequencing a portion of the mitochondrial DNA (mtDNA) control region (CR) I as barcodes is recommended to identify istiophorid (billfish) larvae in the Atlantic Ocean because of its high resolution and the intrinsic value of the levels of genetic variation that can be extracted from these data. The universality of the primers employed here demonstrates their utility for not only the positive identification of istiophorids in the GoM, but for any larval teleost occurring in areas recognized as larval hotspots worldwide.
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