Dust, Ice, and Gas in Time (DIGIT) Herschel Observations of GSS30-IRS1 in Ophiuchus

As a part of the "Dust, Ice, and Gas In Time" (DIGIT) key program on Herschel, we observed GSS30-IRS1, a Class I protostar located in Ophiuchus (d = 120 pc), with Herschel/Photodetector Array Camera and Spectrometer. More than 70 lines were detected within a wavelength range from 50 to 200 mu m, including CO, H2O, OH, and two atomic [O I] lines at 63 and 145 mu m. The [C II] line, known as a tracer of externally heated gas by the interstellar radiation field (ISRF), is also detected at 158 mu m. All lines, except [O I] and [C II], are detected only at the central spaxel of 9 ''.4 x 9 ''.4. The [O I] emissions are extended along a NE-SW orientation, and the [C II] line is detected over all spaxels, indicative of an external photodissociation region. The total [C II] intensity around GSS30 reveals that the far-ultraviolet radiation field is in the range of 3 to 20 G(0), where G(0) is in units of the Habing Field, 1.6 x 10(-3) erg cm(-2) s(-1). This enhanced external radiation field heats the envelope of GSS30-IRS1, causing the continuum emission to be extended, unlike the molecular emission. The best-fit continuum model of GSS30-IRS1 with the physical structure including flared disk, envelope, and outflow shows that the internal luminosity is 10 L-circle dot, and the region is externally heated by a radiation field enhanced by a factor of 130 compared to the standard local ISRF.NASANational Research Foundation of Korea (NRF) - Ministry of Education of the Korean government NRF-2012R1A1A2044689National Research Foundation (NRF) - Ministry of Education of KoreaAstronom

High fludarabine exposure and relationship with treatment-related mortality after nonmyeloablative hematopoietic cell transplantation.

Despite its common use in nonmyeloablative preparative regimens, the pharmacokinetics of fludarabine are poorly characterized in hematopoietic cell transplantation (HCT) recipients and exposure-response relationships remain undefined. The objective of this study was to evaluate the association between plasma F-ara-A exposure, the systemically circulating moiety of fludarabine, and engraftment, acute GVHD, TRM and OS after HCT. The preparative regimen consisted of CY 50 mg/kg/day i.v. day -6; plus fludarabine 30-40 mg/m²/day i.v. on days -6 to -2 and TBI 200 cGy on day -1. F-ara-A pharmacokinetics were carried out with the first dose of fludarabine in 87 adult patients. Median (range) F-ara-A area-under-the-curve (AUC((0-∞))) was 5.0 μg h/mL (2.0-11.0), clearance 15.3 L/h (6.2-36.6), C(min) 55 ng/mL (17-166) and concentration on day(zero) 16.0 ng/mL (0.1-144.1). Despite dose reductions, patients with renal insufficiency had higher F-ara-A exposures. There was strong association between high plasma concentrations of F-ara-A and increased risk of TRM and reduced OS. Patients with an AUC((0-∞)) greater than 6.5 μg h/mL had 4.56 greater risk of TRM and significantly lower OS. These data suggest that clinical strategies are needed to optimize dosing of fludarabine to prevent overexposure and toxicity in HCT

UK COVID-19 lockdown: 100 days of air pollution reduction?

On the 23 March 2020, a country-wide COVID-19 lockdown was imposed on the UK. The following 100 days saw anthropogenic movements quickly halt, before slowly easing back to a “new” normality. In this short communication, we use data from official UK air-quality sensors (DEFRA AURN) and the UK Met Office stations to show how lockdown measures affected air quality in the UK. We compare the 100 days post-lockdown (23 March to 30 June 2020) with the same period from the previous 7 years. We find, as shown in numerous studies of other countries, the nitrogen oxides levels across the country dropped substantially (∼ 50%). However, we also find the ozone levels increased (∼ 10%), and the levels of sulphur dioxide more than doubled across the country. These changes, driven by a complex balance in the air chemistry near the surface, may reflect the influence of low humidity as suggested by Met Office data, and potentially, the reduction of nitrogen oxides and their interactions with multiple pollutants

The anomalous U(1) global symmetry and flavors from an SU(5) x SU(5)′' GUT in Z12−IZ_{12-I} orbifold compactification

In string compactifications, frequently there appears the anomalous U(1) gauge symmetry which belonged to E8$\times$E8 of the heterotic string. This anomalous U(1) gauge boson obtains mass at the compactification scale, just below $10^{18\,}$GeV, by absorbing one pseudoscalar (corresponding to the model-independent axion) from the second rank anti-symmetric tensor field $B_{MN}$. Below the compactification scale, there results a global symmetry U(1)$_{\rm anom}$ whose charge $Q_{\rm anom}$ is the original gauge U(1) charge. This is the most natural global symmetry, realizing the "invisible" axion. This global symmetry U(1)$_{\rm anom}$ is suitable for a flavor symmetry. In the simplest compactification model with the flipped SU(5) grand unification, we calculate all the low energy parameters in terms of the vacuum expectation values of the standard model singlets.Comment: 18 pages, 4 figur

In an in vitro model of human tuberculosis, monocyte-microglial networks regulate matrix metalloproteinase-1 and -3 gene expression and secretion via a p38 mitogen activated protein kinase-dependent pathway.

BACKGROUND: Tuberculosis (TB) of the central nervous system (CNS) is characterized by extensive tissue inflammation, driven by molecules that cleave extracellular matrix such as matrix metalloproteinase (MMP)-1 and MMP-3. However, relatively little is known about the regulation of these MMPs in the CNS. METHODS: Using a cellular model of CNS TB, we stimulated a human microglial cell line (CHME3) with conditioned medium from Mycobacterium tuberculosis-infected primary human monocytes (CoMTb). MMP-1 and MMP-3 secretion was detected using ELISAs confirmed with casein zymography or western blotting. Key results of a phospho-array profile that detects a wide range of kinase activity were confirmed with phospho-Western blotting. Chemical inhibition (SB203580) of microglial cells allowed investigation of expression and secretion of MMP-1 and MMP-3. Finally we used promoter reporter assays employing full length and MMP-3 promoter deletion constructs. Student's t-test was used for comparison of continuous variables and multiple intervention experiments were compared by one-way ANOVA with Tukey's correction for multiple pairwise comparisons. RESULTS: CoMTb up-regulated microglial MMP-1 and MMP-3 secretion in a dose- and time-dependent manner. The phospho-array profiling showed that the major increase in kinase activity due to CoMTb stimulation was in p38 mitogen activated protein kinase (MAPK), principally the α and γ subunits. p38 phosphorylation was detected at 15 minutes, with a second peak of activity at 120 minutes. High basal extracellular signal-regulated kinase activity was further increased by CoMTb. Secretion and expression of MMP-1 and MMP-3 were both p38 dependent. CoMTb stimulation of full length and MMP-3 promoter deletion constructs demonstrated up-regulation of activity in the wild type but a suppression site between -2183 and -1612 bp. CONCLUSIONS: Monocyte-microglial network-dependent MMP-1 and MMP-3 gene expression and secretion are dependent upon p38 MAPK in tuberculosis. p38 is therefore a potential target for adjuvant therapy in CNS TB

K-Bayes Reconstruction for Perfusion MRI II: Modeling and Technical Development

Despite the continued spread of magnetic resonance imaging (MRI) methods in scientific studies and clinical diagnosis, MRI applications are mostly restricted to high-resolution modalities such as structural MRI. While perfusion MRI gives complementary information on blood flow in the brain, its reduced resolution limits its power for detecting specific disease effects on perfusion patterns. This reduced resolution is compounded by artifacts such as partial volume effects, Gibbs ringing, and aliasing, which are caused by necessarily limited k-space sampling and the subsequent use of discrete Fourier transform (DFT) reconstruction. Here, a Bayesian modeling procedure (K-Bayes) is developed for the reconstruction of perfusion MRI. The K-Bayes approach combines a process model for the MRI signal in k-space with a Markov random field prior distribution that incorporates high-resolution segmented structural MRI information. A simulation study, described in Part I (Concepts and Applications), was performed to determine qualitative and quantitative improvements in K-Bayes reconstructed images compared with those obtained via DFT. The improvements were validated using in vivo perfusion MRI data of the human brain. The K-Bayes reconstructed images were demonstrated to provide reduced bias, increased precision, greater effect sizes, and higher resolution than those obtained using DFT