Helium in natal HII regions: the origin of the X-ray absorption in gamma-ray burst afterglows

Soft X-ray absorption in excess of Galactic is observed in the afterglows of most gamma-ray bursts (GRBs), but the correct solution to its origin has not been arrived at after more than a decade of work, preventing its use as a powerful diagnostic tool. We resolve this long-standing problem and find that He in the GRB's host HII region is responsible for most of the absorption. We show that the X-ray absorbing column density (N_Hx) is correlated with both the neutral gas column density and with the optical afterglow extinction (Av). This correlation explains the connection between dark bursts and bursts with high N_Hx values. From these correlations we exclude an origin of the X-ray absorption which is not related to the host galaxy, i.e. the intergalactic medium or intervening absorbers are not responsible. We find that the correlation with the dust column has a strong redshift evolution, whereas the correlation with the neutral gas does not. From this we conclude that the column density of the X-ray absorption is correlated with the total gas column density in the host galaxy rather than the metal column density, in spite of the fact that X-ray absorption is typically dominated by metals. The strong redshift evolution of N_Hx/Av is thus a reflection of the cosmic metallicity evolution of star-forming galaxies. We conclude that the absorption of X-rays in GRB afterglows is caused by He in the HII region hosting the GRB. While dust is destroyed and metals are stripped of all of their electrons by the GRB to great distances, the abundance of He saturates the He-ionising UV continuum much closer to the GRB, allowing it to remain in the neutral or singly-ionised state. Helium X-ray absorption explains the correlation with total gas, the lack of strong evolution with redshift as well as the absence of dust, metal or hydrogen absorption features in the optical-UV spectra.Comment: 10 pages, 4 figures, submitted to Ap

Experimental determination of translational starts using peptide mass mapping and tandem mass spectrometry within the proteome of Mycobacterium tuberculosis

Identification of protein translation start sites is largely a bioinformatics exercise, with relatively few confirmed by N-terminal sequencing. Translation start site determination is critical for defining both the protein sequence and the upstream DNA which may contain regulatory motifs. It is demonstrated here that translation start sites can be determined during routine protein identification, using MALDI-MS and MS/MS data to select the correct N-terminal sequence from a list of alternatives generated in silico. Applying the method to 13 proteins from Mycobacterium tuberculosis, 11 predicted translational start sites were confirmed, and two reassigned. The authors suggest that these data (be they confirmation or reassignments) are important for the annotation of both this genome and those of organisms with related genes. It was also shown that N-acetylation, reported to be rare in prokaryotes, was present in three of the 13 proteins (23 %), suggesting that in the mycobacteria this modification may be common, and an important regulator of protein function, although more proteins need to be analysed. This method can be performed with little or no additional experimental work during proteomics investigations

Development of a Novel Lipophilic, Magnetic Nanoparticle for in Vivo Drug Delivery

The aim of the present study was to evaluate the transfection potential of chitosan-coated, green-fluorescent magnetic nanoparticles (MNPs) (chi-MNPs) after encapsulation inside polyethylglycol (PEG)ylated liposomes that produced lipid-encapsulated chitosan-coated MNPs (lip-MNPs), and also to evaluate how these particles would distribute in vivo after systemic injection. The transfection potential of both chi-MNPs and lip-MNPs was evaluated in vitro in rat brain endothelial 4 (RBE4) cells with and without applying a magnetic field. Subsequently, the MNPs were evaluated in vivo in young rats. The in vitro investigations revealed that the application of a magnetic field resulted in an increased cellular uptake of the particles. The lip-MNPs were able to transfect the RBE4 cells with an incidence of approximately 20% of a commercial transfection agent. The in vivo distribution studies revealed that lip-MNPs had superior pharmacokinetic properties due to evasion of the RES, including hepatic Kuppfer cells and macrophages in the spleen. In conclusion, we were able to design a novel lipid-encapsulated MNP with the ability to carry genetic material, with favorable pharmacokinetic properties, and under the influence of a magnetic field with the capability to mediate transfection in vitro

Non-invasive assessment of temporal changes in myocardial microvascular function in persons with type 2 diabetes and healthy controls

BACKGROUND: Cardiac Rubidium‐82 ((82)Rb) positron emission tomography/computed tomography (PET/CT) provides a measure of the myocardial blood flow and the myocardial flow reserve, which reflects the function of both large epicardial arteries and the myocardial microcirculation. Knowledge on changes in the myocardial microvascular function over time is lacking. METHODS: In this cohort study, we recruited 60 persons with type 2 diabetes and 30 non‐diabetic controls, in 2013; all free of overt cardiovascular disease. All underwent a cardiac (82)Rb PET/CT scan. In 2019, all survivors (n = 82) were invited for a repeated cardiac (82)Rb PET/CT scan using the same protocol, and 29 with type 2 diabetes and 19 controls participated. RESULTS: Median duration between visits was 6.2 years (IQR: 6.1–6.3). In the total cohort, the mean age was 66.4 years (SD: 9.3) and 33% were females. The myocardial flow reserve was lower in persons with type 2 diabetes compared to controls (p = 0.002) but there was no temporal change in the myocardial flow reserve in participants with type 2 diabetes: mean change: −0.22 (95% CI: −0.47 to 0.02) nor in controls: −0.12 (−0.49 to 0.25) or when comparing type 2 diabetes to controls: mean difference: −0.10 (95% CI: −0.52 to 0.31). The temporal reduction in stress‐induced myocardial blood flow did not differ within the groups but was more pronounced in type 2 diabetes compared to controls: mean difference: −0.30 (95% CI: −0.55 to −0.04). CONCLUSION: The myocardial microvascular function was impaired in persons with type 2 diabetes compared to controls but did not change significantly in either of the groups when evaluated over 6 years

Positive and Negative Agglomeration Externalities: Arbitration in the Pig Sector

Abstract In this study we analyse the determinants of pig production location in Denmark with a particular focus on positive and negative agglomeration externalities. Based on the theory of agglomeration and a discussion of the organization of the Danish pig production sector, a model of pig production is developed and tested empirically, applying the FG2SLS approach. Our results show that technical and pecuniary externalities have a positive effect on location, while the impact of environmental regulations is ambiguous. Indeed, the results show that urbanization economies are more important than the negative impact of land competition at the local level, but that neighbouring land competition implied by environmental regulations seems to have a negative effect on location. Externalités d'agglomérations positives et négatives: arbitrage dans le secteur de la production porcine Résumé Dans la présente étude, nous analysons les déterminants de la localisation de la production porcine au Danemark, en insistant tout particulièrement sur les externalités d'agglomération positives et négatives. Nous créons un modèle pour la production porcine, sur la base de la théorie de l'agglomération et de discussions sur l'organisation du secteur de la production porcine au Danemark, et nous le testons de façon empirique, en appliquant la méthode FG2SLS. Nos résultats indiquent que les externalités techniques et pécuniaires ont un effet positif sur la localisation , alors que l'impact des rėglementations environnementales est ambigu. Externalidades de la aglomeración positiva y negativa: arbitraje en el sector porcino Extracto En este estudio analizamos los determinantes de la ubicación de la producción de cerdos en Dinamarca con un enfoque particular en las externalidades de la aglomeración positiva y negativa. Basado en la teoría de la aglomeración y en una discusión sobre la organización del sector de la producción de cerdos danesa, se desarrolla y ensaya empíricamente un modelo de producción de cerdos, aplicando el planteamiento FG2SLS. Nuestros resultados muestran que las externalidades técnicas y pecuniarias tienen un efecto positivo sobre la ubicación, mientras que el impacto de las normativas medioambientales es ambiguo.Agglomeration externalities, spatial econometrics, environmental regulations, C13, R30, R15, Q11,

Mannose-Binding Lectin (MBL) Substitution: Recovery of Opsonic Function In Vivo Lags behind MBL Serum Levels

Mannose-binding lectin (MBL) deficiency is often associated with an increased risk of infection or worse prognosis in immuno-compromised patients. MBL substitution in these patients might diminish these risks. We therefore performed an open, uncontrolled safety and pharmacokinetic MBL-substitution study in 12 pediatric oncology patients with chemotherapy-induced neutropenia. Twice weekly MBL infusions with plasma-derived MBL yielded MBL trough levels > 1.0 mu g/ml. We tested whether MBL substitution in vivo increased MBL-dependent complement activation and opsonophagocytosis of zymosan in vitro. Upon MBL substitution, opsonophagocytosis by control neutrophils increased significantly (p <0.001) but remained suboptimal, although repeated MBL infusions resulted in improvement over time. The MBL-dependent MBL-associated serine protease (MASP)mediated complement C3 and C4 activation also showed a suboptimal increase. To explain these results, complement activation was studied in detail. We found that in the presence of normal MASP-2 blood levels, MASP-2 activity (p <0.0001) was reduced as well as the alternative pathway of complement activation (p <0.05). This MBL-substitution study demonstrates that plasma-derived MBL infusions increase MBL/MASP-mediated C3 and C4 activation and opsonophagocytosis, but that higher circulating levels of plasma-derived MBL are required to achieve MBL-mediated complement activation comparable to healthy controls. Other patient cohorts should be considered to demonstrate clinical efficacy in phase II/III MBL-substitution studies, because we found a suboptimal recovery of (in vitro) biological activity upon MBL substitution in our neutropenic pediatric oncology cohort. The Journal of Immunology, 2009, 183: 3496-350