On the Commonality of 10-30AU Sized Axisymmetric Dust Structures in Protoplanetary Disks

An unsolved problem in step-wise core-accretion planet formation is that rapid radial drift in gas-rich protoplanetary disks should drive millimeter-/meter-sized particles inward to the central star before large bodies can form. One promising solution is to confine solids within small-scale structures. Here, we investigate dust structures in the (sub)millimeter continuum emission of four disks (TW Hya, HL Tau, HD 163296, and DM Tau), a sample of disks with the highest spatial resolution Atacama Large Millimeter/submillimeter Array observations to date. We retrieve the surface brightness distributions using synthesized images and fitting visibilities with analytical functions. We find that the continuum emission of the four disks is ~axisymmetric but rich in 10–30 AU-sized radial structures, possibly due to physical gaps, surface density enhancements, or localized dust opacity variations within the disks. These results suggest that small-scale axisymmetric dust structures are likely to be common, as a result of ubiquitous processes in disk evolution and planet formation. Compared with recent spatially resolved observations of CO snow lines in these same disks, all four systems show enhanced continuum emission from regions just beyond the CO condensation fronts, potentially suggesting a causal relationship between dust growth/trapping and snow lines

Metatranscriptome analysis of the microbial fermentation of dietary milk proteins in the murine gut

Undigestible food ingredients are converted by the microbiota into a large range of metabolites, predominated by short chain fatty acids (SCFA). These microbial metabolites are subsequently available for absorption by the host mucosa and can serve as an energy source. Amino acids fermentation by the microbiota expands the spectrum of fermentation end-products beyond acetate, propionate and butyrate, to include in particular branched-SCFA. Here the long-term effects of high protein-diets on microbial community composition and functionality in mice were analyzed. Determinations of the microbiota composition using phylogenetic microarray (MITChip) technology were complemented with metatranscriptome and SCFA analyses to obtain insight in in situ expression of protein fermentation pathways and the phylogenetic groups involved. High protein diets led to increased luminal concentrations of branched-SCFA, in accordance with protein fermentation in the gut. Bacteria dominantly participating in protein catabolism belonged to the Lachnospiraceae, Erysipelotrichaceae and Clostridiaceae families in both normal- and high- protein diet regimes. This study identifies the microbial groups involved in protein catabolism in the intestine and underpins the value of in situ metatranscriptome analyses as an approach to decipher locally active metabolic networks and pathways as a function of the dietary regime, as well as the phylogeny of the microorganisms executing them

Dynamical analysis of bacteria in microscopy movies

Recent advances in microscopy, computing power and image processing have enabled the analysis of ever larger datasets of movies of microorganisms to study their behaviour. However, techniques for analysing the dynamics of individual cells from such datasets are not yet widely available in the public domain. We recently demonstrated significant phenotypic heterogeneity in the adhesion of Escherichia coli bacteria to glass surfaces using a new method for the high-throughput analysis of video microscopy data. Here, we present an in-depth analysis of this method and its limitations, and make public our algorithms for following the positions and orientations of individual rod-shaped bacteria from time-series of 2D images to reconstruct their trajectories and characterise their dynamics. We demonstrate in detail how to use these algorithms to identify different types of adhesive dynamics within a clonal population of bacteria sedimenting onto a surface. The effects of measurement errors in cell positions and of limited trajectory durations on our results are discussed

Investigating the Associations among Overtime Work, Health Behaviors, and Health: A Longitudinal Study among Full-time Employees

# The Author(s) 2010. This article is published with open access at Springerlink.com Background It has often been suggested that high levels of overtime lead to adverse health outcomes. One mechanism that may account for this association is that working overtime leads to elevated levels of stress, which could affect worker’s behavioral decisions or habits (such as smoking and lack of physical activity). In turn, this could lead to adverse health. Purpose The present study examined this reasoning in a prospective longitudinal design. Data from the prospective 2-year Study on Health at Work (N=649) were used to test our hypotheses. Methods Structural equation analysis was used to examine the relationships among overtime, beneficial (exercising, intake of fruit and vegetables) and risky (smoking and drinking) health behaviors, and health indicators (BMI and subjective health). Results Working overtime was longitudinally related with adverse subjective health, but not with body mass

First detection of gas-phase ammonia in a planet-forming disk. NH₃, N₂H⁺, and H₂O in the disk around TW Hydrae

Context. Nitrogen chemistry in protoplanetary disks and the freeze-out on dust particles is key for understanding the formation of nitrogen-bearing species in early solar system analogs. In dense cores, 10% to 20% of the nitrogen reservoir is locked up in ices such as NH3, NH4+ and OCN−. So far, ammonia has not been detected beyond the snowline in protoplanetary disks. Aims. We aim to find gas-phase ammonia in a protoplanetary disk and characterize its abundance with respect to water vapor. Methods. Using HIFI on the Herschel Space Observatory, we detected for the first time the ground-state rotational emission of ortho-NH3 in a protoplanetary disk around TW Hya. We used detailed models of the disk’s physical structure and the chemistry of ammonia and water to infer the amounts of gas-phase molecules of these species. We explored two radial distributions (extended across the disk and confined to <60 au like the millimeter-sized grains) and two vertical distributions (near the midplane and at intermediate heights above the midplane, where water is expected to photodesorb off icy grains) to describe the (unknown) location of the molecules. These distributions capture the effects of radial drift and vertical settling of ice-covered grains. Results. The NH310–00 line is detected simultaneously with H2O 110–101 at an antenna temperature of 15.3 mK in the Herschel beam; the same spectrum also contains the N2H+ 6–5 line with a strength of 18.1 mK. We use physical-chemical models to reproduce the fluxes and assume that water and ammonia are cospatial. We infer ammonia gas-phase masses of 0.7−11.0 × 1021 g, depending on the adopted spatial distribution, in line with previous literature estimates. For water, we infer gas-phase masses of 0.2−16.0 × 1022 g, improving upon earlier literature estimates This corresponds to NH3/H2O abundance ratios of 7%−84%, assuming that water and ammonia are co-located. The inferred N2H+ gas mass of 4.9 × 1021 g agrees well with earlier literature estimates that were based on lower excitation transitions. These masses correspond to a disk-averaged abundances of 0.2−17.0 × 10-11, 0.1−9.0 × 10-10 and 7.6 × 10-11 for NH3, H2O and N2H+ respectively. Conclusions. Only in the most compact and settled adopted configuration is the inferred NH3/H2O consistent with interstellar ices and solar system bodies of ~5%–10%; all other spatial distributions require additional gas-phase NH3 production mechanisms. Volatile release in the midplane may occur through collisions between icy bodies if the available surface for subsequent freeze-out is significantly reduced, for instance, through growth of small grains into pebbles or larger bodies

A LOFAR observation of ionospheric scintillation from two simultaneous travelling ionospheric disturbances

This paper presents the results from one of the first observations of ionospheric scintillation taken using the Low-Frequency Array (LOFAR). The observation was of the strong natural radio source Cassiopeia A, taken overnight on 18–19 August 2013, and exhibited moderately strong scattering effects in dynamic spectra of intensity received across an observing bandwidth of 10–80 MHz. Delay-Doppler spectra (the 2-D FFT of the dynamic spectrum) from the first hour of observation showed two discrete parabolic arcs, one with a steep curvature and the other shallow, which can be used to provide estimates of the distance to, and velocity of, the scattering plasma. A cross-correlation analysis of data received by the dense array of stations in the LOFAR “core” reveals two different velocities in the scintillation pattern: a primary velocity of ~20–40 ms−1 with a north-west to south-east direction, associated with the steep parabolic arc and a scattering altitude in the F-region or higher, and a secondary velocity of ~110 ms−1 with a north-east to south-west direction, associated with the shallow arc and a scattering altitude in the D-region. Geomagnetic activity was low in the mid-latitudes at the time, but a weak sub-storm at high latitudes reached its peak at the start of the observation. An analysis of Global Navigation Satellite Systems (GNSS) and ionosonde data from the time reveals a larger-scale travelling ionospheric disturbance (TID), possibly the result of the high-latitude activity, travelling in the north-west to south-east direction, and, simultaneously, a smaller-scale TID travelling in a north-east to south-west direction, which could be associated with atmospheric gravity wave activity. The LOFAR observation shows scattering from both TIDs, at different altitudes and propagating in different directions. To the best of our knowledge this is the first time that such a phenomenon has been reported

A novel antifolate suppresses growth of FPGS-deficient cells and overcomes methotrexate resistance

Cancer cells make extensive use of the folate cycle to sustain increased anabolic metabolism. Multiple chemotherapeutic drugs interfere with the folate cycle, including methotrexate and 5-fluorouracil that are commonly applied for the treatment of leukemia and colorectal cancer (CRC), respectively. Despite high success rates, therapy-induced resistance causes relapse at later disease stages. Depletion of folylpolyglutamate synthetase (FPGS), which normally promotes intracellular accumulation and activity of natural folates and methotrexate, is linked to methotrexate and 5-fluorouracil resistance and its association with relapse illustrates the need for improved intervention strategies. Here, we describe a novel antifolate (C1) that, like methotrexate, potently inhibits dihydrofolate reductase and downstream one-carbon metabolism. Contrary to methotrexate, C1 displays optimal efficacy in FPGS-deficient contexts, due to decreased competition with intracellular folates for interaction with dihydrofolate reductase. We show that FPGS-deficient patient-derived CRC organoids display enhanced sensitivity to C1, whereas FPGS-high CRC organoids are more sensitive to methotrexate. Our results argue that polyglutamylation-independent antifolates can be applied to exert selective pressure on FPGS-deficient cells during chemotherapy, using a vulnerability created by polyglutamylation deficiency

A novel antifolate suppresses growth of FPGS-deficient cells and overcomes methotrexate resistance

Cancer cells make extensive use of the folate cycle to sustain increased anabolic metabolism. Multiple chemotherapeutic drugs interfere with the folate cycle, including methotrexate and 5-fluorouracil that are commonly applied for the treatment of leukemia and colorectal cancer (CRC), respectively. Despite high success rates, therapy-induced resistance causes relapse at later disease stages. Depletion of folylpolyglutamate synthetase (FPGS), which normally promotes intracellular accumulation and activity of natural folates and methotrexate, is linked to methotrexate and 5-fluorouracil resistance and its association with relapse illustrates the need for improved intervention strategies. Here, we describe a novel antifolate (C1) that, like methotrexate, potently inhibits dihydrofolate reductase and downstream one-carbon metabolism. Contrary to methotrexate, C1 displays optimal efficacy in FPGS-deficient contexts, due to decreased competition with intracellular folates for interaction with dihydrofolate reductase. We show that FPGS-deficient patient-derived CRC organoids display enhanced sensitivity to C1, whereas FPGS-high CRC organoids are more sensitive to methotrexate. Our results argue that polyglutamylation-independent antifolates can be applied to exert selective pressure on FPGS-deficient cells during chemotherapy, using a vulnerability created by polyglutamylation deficiency