Aims. We observationally investigate the relation between the photoelectric heating efficiency in photodissociation regions (PDRs) and the charge of polycyclic aromatic hydrocarbons (PAHs), which are ...considered to play a key role in photoelectric heating. Methods. Using PACS onboard Herschel, we observed six PDRs spanning a wide range of far-ultraviolet radiation fields (G0 = 100−105). To measure the photoelectric heating efficiency, we obtained the intensities of the main cooling lines in these PDRs, i.e., the O i 63 μm, 145 μm, and C ii 158 μm, as well as the far-infrared (FIR) continuum intensity. We used Spitzer/IRS spectroscopic mapping observations to investigate the mid-infrared (MIR; 5.5−14 μm) PAH features in the same regions. We decomposed the MIR PAH emission into that of neutral (PAH0) and positively ionized (PAH+) species to derive the fraction of the positively charged PAHs in each region, and compare it to the photoelectric heating efficiency. Results. The heating efficiency traced by (O i 63 μm + O i 145 μm + C ii 158 μm)/TIR, where TIR is the total infrared flux, ranges between 0.1% and 0.9% in different sources, and the fraction of PAH+ relative to (PAH0+ PAH+) spans from 0 (+11)% to 87 (±10)%. All positions with a high PAH+ fraction show a low heating efficiency, and all positions with a high heating efficiency have a low PAH+ fraction, supporting the scenario in which a positive grain charge results in a decreased heating efficiency. Theoretical estimates of the photoelectric heating efficiency show a stronger dependence on the charging parameter γ = G0T1/2/ne than the observed efficiency reported in this study, and the discrepancy is significant at low γ. The photoelectric heating efficiency on PAHs, traced by (O i 63 μm + O i 145 μm + C ii 158 μm)/(PAH-band emission + O i 63 μm + O i 145 μm + C ii 158 μm), shows a much better match between the observations and the theoretical estimates. Conclusions. The good agreement of the photoelectric heating efficiency on PAHs with a theoretical model indicates the dominant contribution of PAHs to the photoelectric heating. This study demonstrates the fundamental role that PAHs have in photoelectric heating. More studies of their charging behavior are crucial to understand the thermal balance of the interstellar medium.
The metastatic process in breast cancer is related to the expression of the epithelial-to-mesenchymal transition transcription factors (EMT-TFs) SNAIL, SLUG, SIP1 and TWIST1. EMT-TFs and nuclear ...factor-κB (NF-κB) activation have been associated with aggressiveness and metastatic potential in carcinomas. Here, we sought to examine the role of NF-κB in the aggressive properties and regulation of EMT-TFs in human breast cancer cells. Blocking NF-κB/p65 activity by reducing its transcript and protein levels (through siRNA-strategy and dehydroxymethylepoxyquinomicin DHMEQ treatment) in the aggressive MDA-MB-231 and HCC-1954 cell lines resulted in decreased invasiveness and migration, a downregulation of SLUG, SIP1, TWIST1, MMP11 and N-cadherin transcripts and an upregulation of E-cadherin transcripts. No significant changes were observed in the less aggressive cell line MCF-7. Bioinformatics tools identified several NF-κB binding sites along the promoters of SNAIL, SLUG, SIP1 and TWIST1 genes. Through chromatin immunoprecipitation and luciferase reporter assays, the NF-κB/p65 binding on TWIST1, SLUG and SIP1 promoter regions was confirmed. Thus, we suggest that NF-κB directly regulates the transcription of EMT-TF genes in breast cancer. Our findings may contribute to a greater understanding of the metastatic process of this neoplasia and highlight NF-κB as a potential target for breast cancer treatment.
We present a statistical analysis of the environments of 11 supernovae (SNe) which occurred in six nearby galaxies (z ... 0.016). All galaxies were observed with MUSE, the high spatial resolution ...integral-field spectrograph mounted to the 8 m VLT UT4. These data enable us to map the full spatial extent of host galaxies up to ~3 effective radii. In this way, not only can one characterize the specific host environment of each SN, one can compare their properties with stellar populations within the full range of other environments within the host. We present a method that consists of selecting all H II regions found within host galaxies from 2D extinction-corrected H alpha emission maps. These regions are then characterized in terms of their H alpha equivalent widths, star formation rates and oxygen abundances. Identifying H II regions spatially coincident with SN explosion sites, we are thus able to determine where within the distributions of host galaxy e.g. metallicities and ages each SN is found, thus providing new constraints on SN progenitor properties. This initial pilot study using MUSE opens the way for a revolution in SN environment studies where we are now able to study multiple environment SN progenitor dependencies using a single instrument and single pointing. (ProQuest: ... denotes formulae/symbols omitted.)
We calculate the nonreciprocal critical current and quantify the supercurrent diode effect in two-dimensional Rashba superconductors with arbitrary disorder, using the quasiclassical Eilenberger ...equation. The nonreciprocity is caused by the helical superconducting state, which appears when both inversion and time-reversal symmetries are broken. In the absence of disorder, we find a very strong diode effect, with the nonreciprocity exceeding 40% at optimal temperatures, magnetic fields, and spin-orbit coupling. We establish that the effect persists even in the presence of strong disorder. We show that the sign of the diode effect changes as magnetic field and disorder are increased, reflecting the changes in the nature of the helical state.
Photonic entanglement swapping, the procedure of entangling photons without any direct interaction, is a fundamental test of quantum mechanics and an essential resource to the realization of quantum ...networks. Probabilistic sources of nonclassical light were used for seminal demonstration of entanglement swapping, but applications in quantum technologies demand push-button operation requiring single quantum emitters. This, however, turned out to be an extraordinary challenge due to the stringent prerequisites on the efficiency and purity of the generation of entangled states. Here we show a proof-of-concept demonstration of all-photonic entanglement swapping with pairs of polarization-entangled photons generated on demand by a GaAs quantum dot without spectral and temporal filtering. Moreover, we develop a theoretical model that quantitatively reproduces the experimental data and provides insights on the critical figures of merit for the performance of the swapping operation. Our theoretical analysis also indicates how to improve state-of-the-art entangled-photon sources to meet the requirements needed for implementation of quantum dots in long-distance quantum communication protocols.
DNA encoded libraries (DELs) represent powerful new technology for finding small molecule ligands for proteins and are increasingly being applied to hit finding in medicinal chemistry. Crucial to the ...synthesis of high quality DELs is the identification of chemical reactions for their assembly that proceed with very high conversion across a range of different substrates, under conditions compatible with DNA-tagged substrates. Many current chemistries used in DEL synthesis do not meet this requirement, resulting in libraries of low fidelity. Amide couplings are the most commonly used reaction in synthesis of screening libraries and also in DELs. The ability to carry out highly efficient, widely applicable amide couplings in DEL synthesis would therefore be highly desirable. We report a method for amide coupling using micelle forming surfactants, promoted by a modified linker, that is broadly applicable across a wide range of substrates. Most significantly, this works exceptionally well for coupling of DNA-conjugated carboxylic acids (N-to-C) with amines in solution, a procedure that is currently very inefficient. The optimisation of separate procedures for coupling of DNA-conjugated acids and amines by reagent screening and statistically driven optimisation is described. The generality of the method is illustrated by the application to a wide range of examples with unprecedented levels of conversion. The utility of the (N-to-C) coupling of DNA-conjugated acids in DEL synthesis is illustrated by the three cycle synthesis of a fully DNA-encoded compound by two cycles of coupling of an aminoester, with intermediate ester hydrolysis, followed by capping with an amine. This methodology will be of great utility in the synthesis of high fidelity DELs.
Highly efficient forward and reverse on-DNA amide couplings were developed exploiting hydrophobic linkers in combination with the micelle forming surfactant TPGS-750M. The method is highly effective for a wide range of substrates in the synthesis of DNA-encoded libraries.
We present the first subarcsecond-resolution mid-infrared (MIR) atlas of local active galactic nuclei (AGN). Our atlas contains 253 AGN with a median redshift of z = 0.016, and includes all publicly ...available MIR imaging performed to date with ground-based 8-m class telescopes, a total of 895 independent measurements. Of these, more than 60 per cent are published here for the first time. We detect extended nuclear emission in at least 21 per cent of the objects, while another 19 per cent appear clearly point-like, and the remaining objects cannot be constrained. Where present, elongated nuclear emission aligns with the ionization cones in Seyferts. Subarcsecond resolution allows us to isolate the AGN emission on scales of a few tens of parsecs and to obtain nuclear photometry in multiple filters for the objects. Median spectral energy distributions (SEDs) for the different optical AGN types are constructed and individual MIR 12 and 18 μm continuum luminosities are computed. These range over more than six orders of magnitude. In comparison to the arcsecond-scale MIR emission as probed by Spitzer, the continuum emission is much lower on subarcsecond scales in many cases. The silicate feature strength is similar on both scales and generally appears in emission (absorption) in type I (II) AGN. However, the polycyclic aromatic hydrocarbon emission appears weaker or absent on subarcsecond scales. The differences of the MIR SEDs on both scales are particularly large for AGN/starburst composites and close-by (and weak) AGN. The nucleus dominates over the total emission of the galaxy only at luminosities 1044 erg s−1. The AGN MIR atlas is well suited not only for detailed investigation of individual sources but also for statistical studies of AGN unification.
In 2019, a novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which is transmitted via the airborne route, caused a new pandemic namely, "coronavirus disease 2019" (COVID-19). ...Although the effectiveness of face masks to prevent the transmission of SARS-CoV-2 is debated, no study has evaluated the virus-blocking efficacy of masks used by patients. We aimed to evaluate this efficacy of masks used by SARS-CoV-2-infected individuals. Data, masks used, and nasopharyngeal swab samples were obtained from these patients. Forty-five paired samples of nasopharyngeal swabs and masks were obtained and processed; the majority of masks were woven. Viral RNAs were amplified using quantitative reverse-transcription polymerase chain reaction and detected only on the inner parts of masks. Median viral load (VL) values of swabs and masks were 1.954x106 and 2,51x103, respectively. Statistically, there was a difference of approximately 1000 RNA copies/mL between swabs and masks and no significant difference in VL values among different types of masks. There were statistically significant differences in VL values between men and women and between symptomatic and asymptomatic patients. Our findings suggest the blocking of virus transmission by different types of masks and reinforce the use of masks by both infected and non-infected individuals.
1. P-glycoprotein (P-gp/MDR1), one of the most clinically important transmembrane transporters in humans, is encoded by the ABCB1/MDR1 gene. Recent insights into the structural features of P-gp/MDR1 ...enable a re-evaluation of the biochemical evidence on the binding and transport of drugs by P-gp/MDR1.
2. P-gp/MDR1 is found in various human tissues in addition to being expressed in tumours cells. It is located on the apical surface of intestinal epithelial cells, bile canaliculi, renal tubular cells, and placenta and the luminal surface of capillary endothelial cells in the brain and testes.
3. P-gp/MDR1 confers a multi-drug resistance (MDR) phenotype to cancer cells that have developed resistance to chemotherapy drugs. P-gp/MDR1 activity is also of great clinical importance in non-cancer-related drug therapy due to its wide-ranging effects on the absorption and excretion of a variety of drugs.
4. P-gp/MDR1 excretes xenobiotics such as cytotoxic compounds into the gastrointestinal tract, bile and urine. It also participates in the function of the blood-brain barrier.
5. One of the most interesting characteristics of P-gp/MDR1 is that its many substrates vary greatly in their structure and functionality, ranging from small molecules such as organic cations, carbohydrates, amino acids and some antibiotics to macromolecules such as polysaccharides and proteins.
6. Quite a number of single nucleotide polymorphisms have been found for the MDR1 gene. These single nucleotide polymorphisms are associated with altered oral bioavailability of P-gp/MDR1 substrates, drug resistance, and a susceptibility to some human diseases.
7. Altered P-gp/MDR1 activity due to induction and/or inhibition can cause drug-drug interactions with altered drug pharmacokinetics and response.
8. Further studies are warranted to explore the physiological function and pharmacological role of P-gp/MDR1.
Context. Deep far-infrared (FIR) cosmological surveys are known to be affected by source confusion, causing issues when examining the main sequence (MS) of star forming galaxies. In the past this has ...typically been partially tackled by the use of stacking. However, stacking only provides the average properties of the objects in the stack. Aims. This work aims to trace the MS over 0.2 ≤ z < 6.0 using the latest de-blended Herschel photometry, which reaches ≈10 times deeper than the 5σ confusion limit in SPIRE. This provides more reliable star formation rates (SFRs), especially for the fainter galaxies, and hence a more reliable MS. Methods. We built a pipeline that uses the spectral energy distribution (SED) modelling and fitting tool CIGALE to generate flux density priors in the Herschel SPIRE bands. These priors were then fed into the de-blending tool XID+ to extract flux densities from the SPIRE maps. In the final step, multi-wavelength data were combined with the extracted SPIRE flux densities to constrain SEDs and provide stellar mass (M⋆) and SFRs. These M⋆ and SFRs were then used to populate the SFR-M⋆ plane over 0.2 ≤ z < 6.0. Results. No significant evidence of a high-mass turn-over was found; the best fit is thus a simple two-parameter power law of the form log(SFR) = αlog(M⋆) − 10.5 + β. The normalisation of the power law increases with redshift, rapidly at z ≲ 1.8, from 0.58 ± 0.09 at z ≈ 0.37 to 1.31 ± 0.08 at z ≈ 1.8. The slope is also found to increase with redshift, perhaps with an excess around 1.8 ≤ z < 2.9. Conclusions. The increasing slope indicates that galaxies become more self-similar as redshift increases. This implies that the specific SFR of high-mass galaxies increases with redshift, from 0.2 to 6.0, becoming closer to that of low-mass galaxies. The excess in the slope at 1.8 ≤ z < 2.9, if present, coincides with the peak of the cosmic star formation history.