Gamma-Ray Telescopes (in "400 Years of Astronomical Telescopes")

The last half-century has seen dramatic developments in gamma-ray telescopes, from their initial conception and development through to their blossoming into full maturity as a potent research tool in astronomy. Gamma-ray telescopes are leading research in diverse areas such as gamma-ray bursts, blazars, Galactic transients, and the Galactic distribution of aluminum-26.Comment: 11 pages, 6 figures/ in "400 Years of Astronomical Telescopes: A Review of History, Science and Technology", ed. B.R. Brandl, R. Stuik, & J.K. Katgert-Merkeli (Exp. Astron. 26, 111-122 [2009]

Ambient Particulate Matter Air Pollution and Venous Thromboembolism in the Women’s Health Initiative Hormone Therapy Trials

BackgroundThe putative effects of postmenopausal hormone therapy on the association between particulate matter (PM) air pollution and venous thromboembolism (VTE) have not been assessed in a randomized trial of hormone therapy, despite its widespread use among postmenopausal women.ObjectiveIn this study, we examined whether hormone therapy modifies the association of PM with VTE risk.MethodsPostmenopausal women 50–79 years of age (n = 26,450) who did not have a history of VTE and who were not taking anticoagulants were enrolled in the Women’s Health Initiative Hormone Therapy trials at 40 geographically diverse U.S. clinical centers. The women were randomized to treatment with estrogen versus placebo (E trial) or to estrogen plus progestin versus placebo (E + P trial). We used age-stratified Cox proportional hazard models to examine the association between time to incident, centrally adjudicated VTE, and daily mean PM concentrations spatially interpolated at geocoded addresses of the participants and averaged over 1, 7, 30, and 365 days.ResultsDuring the follow-up period (mean, 7.7 years), 508 participants (2.0%) had VTEs at a rate of 2.6 events per 1,000 person-years. Unadjusted and covariate-adjusted VTE risk was not associated with concentrations of PM 0.05) regardless of PM averaging period, either before or after combining data from both trials [e.g., combined trial-adjusted hazard ratios (95% confidence intervals) per 10 μg/m3 increase in annual mean PM2.5 and PM10, were 0.93 (0.54–1.60) and 1.05 (0.72–1.53), respectively]. Findings were insensitive to alternative exposure metrics, outcome definitions, time scales, analytic methods, and censoring dates.ConclusionsIn contrast to prior research, our findings provide little evidence of an association between short-term or long-term PM exposure and VTE, or clinically important modification by randomized exposure to exogenous estrogens among postmenopausal women

TOPOLOGICAL DEFECTS AND HIGHEST ENERGY COSMIC AND GAMMA RAYS

In this paper we review the hypothesis that a considerable part of the cosmic ray flux observed above about 10^{19}\eV may be produced by decaying or annihilating topological defects left over from phase transitions in the early universe at grand unification energy scales (\approx10^{16}\GeV). Possible signatures of cosmic ray producing defect models are discussed which could be tested experimentally in the near future. We thereby focus on model independent universal spectral properties of the predicted particle fluxes.Comment: 11 pages of uuencoded compressed postscript, including 3 figures, to be published in Space Science Reviews

Prospective study evaluating the relative sensitivity of 18F-NaF PET/CT for detecting skeletal metastases from renal cell carcinoma in comparison to multidetector CT and 99mTc-MDP bone scintigraphy, using an adaptive trial design.

BACKGROUND: The detection of occult bone metastases is a key factor in determining the management of patients with renal cell carcinoma (RCC), especially when curative surgery is considered. This prospective study assessed the sensitivity of (18)F-labelled sodium fluoride in conjunction with positron emission tomography/computed tomography ((18)F-NaF PET/CT) for detecting RCC bone metastases, compared with conventional imaging by bone scintigraphy or CT. PATIENTS AND METHODS: An adaptive two-stage trial design was utilized, which was stopped after the first stage due to statistical efficacy. Ten patients with stage IV RCC and bone metastases were imaged with (18)F-NaF PET/CT and (99m)Tc-labelled methylene diphosphonate ((99m)Tc-MDP) bone scintigraphy including pelvic single photon emission computed tomography (SPECT). Images were reported independently by experienced radiologists and nuclear medicine physicians using a 5-point scoring system. RESULTS: Seventy-seven lesions were diagnosed as malignant: 100% were identified by (18)F-NaF PET/CT, 46% by CT and 29% by bone scintigraphy/SPECT. Standard-of-care imaging with CT and bone scintigraphy identified 65% of the metastases reported by (18)F-NaF PET/CT. On an individual patient basis, (18)F-NaF PET/CT detected more RCC metastases than (99m)Tc-MDP bone scintigraphy/SPECT or CT alone (P = 0.007). The metabolic volumes, mean and maximum standardized uptake values (SUV mean and SUV max) of the malignant lesions were significantly greater than those of the benign lesions (P < 0.001). CONCLUSIONS: (18)F-NaF PET/CT is significantly more sensitive at detecting RCC skeletal metastases than conventional bone scintigraphy or CT. The detection of occult bone metastases could greatly alter patient management, particularly in the context when standard-of-care imaging is negative for skeletal metastases.This work was supported by Cancer Research UK [grant number C19212/A16628]. The authors also received research support from the National Institute of Health Research Cambridge Biomedical Research Centre, Engineering and Physical Sciences Research Council Imaging Centre in Cambridge and Manchester, and the Cambridge Experimental Cancer Medicine Centre. The research has also been partly funded by a generous donation from the family and friends of a patient.This is the final version of the article. It first appeared from Oxford University Press via http://dx.doi.org/10.1093/annonc/mdv28

A transcriptomic snapshot of early molecular communication between Pasteuria penetrans and Meloidogyne incognita

© The Author(s). 2018Background: Southern root-knot nematode Meloidogyne incognita (Kofoid and White, 1919), Chitwood, 1949 is a key pest of agricultural crops. Pasteuria penetrans is a hyperparasitic bacterium capable of suppressing the nematode reproduction, and represents a typical coevolved pathogen-hyperparasite system. Attachment of Pasteuria endospores to the cuticle of second-stage nematode juveniles is the first and pivotal step in the bacterial infection. RNA-Seq was used to understand the early transcriptional response of the root-knot nematode at 8 h post Pasteuria endospore attachment. Results: A total of 52,485 transcripts were assembled from the high quality (HQ) reads, out of which 582 transcripts were found differentially expressed in the Pasteuria endospore encumbered J2 s, of which 229 were up-regulated and 353 were down-regulated. Pasteuria infection caused a suppression of the protein synthesis machinery of the nematode. Several of the differentially expressed transcripts were putatively involved in nematode innate immunity, signaling, stress responses, endospore attachment process and post-attachment behavioral modification of the juveniles. The expression profiles of fifteen selected transcripts were validated to be true by the qRT PCR. RNAi based silencing of transcripts coding for fructose bisphosphate aldolase and glucosyl transferase caused a reduction in endospore attachment as compared to the controls, whereas, silencing of aspartic protease and ubiquitin coding transcripts resulted in higher incidence of endospore attachment on the nematode cuticle. Conclusions: Here we provide evidence of an early transcriptional response by the nematode upon infection by Pasteuria prior to root invasion. We found that adhesion of Pasteuria endospores to the cuticle induced a down-regulated protein response in the nematode. In addition, we show that fructose bisphosphate aldolase, glucosyl transferase, aspartic protease and ubiquitin coding transcripts are involved in modulating the endospore attachment on the nematode cuticle. Our results add new and significant information to the existing knowledge on early molecular interaction between M. incognita and P. penetrans.Peer reviewedFinal Published versio

The Correlation between Mixing Length and Metallicity on the Giant Branch: Implications for Ages in the Gaia Era

In the updated APOGEE-Kepler catalog, we have asteroseismic and spectroscopic data for over 3000 first ascent red giants. Given the size and accuracy of this sample, these data offer an unprecedented test of the accuracy of stellar models on the post-main-sequence. When we compare these data to theoretical predictions, we find a metallicity dependent temperature offset with a slope of around 100 K per dex in metallicity. We find that this effect is present in all model grids tested, and that theoretical uncertainties in the models, correlated spectroscopic errors, and shifts in the asteroseismic mass scale are insufficient to explain this effect. Stellar models can be brought into agreement with the data if a metallicity-dependent convective mixing length is used, with Delta alpha(ML), YREC similar to 0.2 per dex in metallicity, a trend inconsistent with the predictions of three-dimensional stellar convection simulations. If this effect is not taken into account, isochrone ages for red giants from the Gaia data will be off by as much as a factor of two even at modest deviations from solar metallicity ([Fe/H]- -0.5)

Hypermutable Non-Synonymous Sites Are under Stronger Negative Selection

Mutation rate varies greatly between nucleotide sites of the human genome and depends both on the global genomic location and the local sequence context of a site. In particular, CpG context elevates the mutation rate by an order of magnitude. Mutations also vary widely in their effect on the molecular function, phenotype, and fitness. Independence of the probability of occurrence of a new mutation's effect has been a fundamental premise in genetics. However, highly mutable contexts may be preserved by negative selection at important sites but destroyed by mutation at sites under no selection. Thus, there may be a positive correlation between the rate of mutations at a nucleotide site and the magnitude of their effect on fitness. We studied the impact of CpG context on the rate of human–chimpanzee divergence and on intrahuman nucleotide diversity at non-synonymous coding sites. We compared nucleotides that occupy identical positions within codons of identical amino acids and only differ by being within versus outside CpG context. Nucleotides within CpG context are under a stronger negative selection, as revealed by their lower, proportionally to the mutation rate, rate of evolution and nucleotide diversity. In particular, the probability of fixation of a non-synonymous transition at a CpG site is two times lower than at a CpG site. Thus, sites with different mutation rates are not necessarily selectively equivalent. This suggests that the mutation rate may complement sequence conservation as a characteristic predictive of functional importance of nucleotide sites

DNA methylation regulates expression of VEGF-R2 (KDR) and VEGF-R3 (FLT4)

Abstract Background Vascular Endothelial Growth Factors (VEGFs) and their receptors (VEGF-Rs) are important regulators for angiogenesis and lymphangiogenesis. VEGFs and VEGF-Rs are not only expressed on endothelial cells but also on various subtypes of solid tumors and leukemias contributing to the growth of the malignant cells. This study was performed to examine whether VEGF-R2 (KDR) and VEGF-R3 (FLT4) are regulated by DNA methylation. Methods Real-time (RT) PCR analysis was performed to quantify KDR and FLT4 expression in some ninety leukemia/lymphoma cell lines, human umbilical vein endothelial cells (HUVECs) and dermal microvascular endothelial cells (HDMECs). Western blot analyses and flow cytometric analyses confirmed results at the protein level. After bisulfite conversion of DNA we determined the methylation status of KDR and FLT4 by DNA sequencing and by methylation specific PCR (MSP). Western blot analyses were performed to examine the effect of VEGF-C on p42/44 MAPK activation. Results Expression of KDR and FLT4 was observed in cell lines from various leukemic entities, but not in lymphoma cell lines: 16% (10/62) of the leukemia cell lines expressed KDR, 42% (27/65) were FLT4 positive. None of thirty cell lines representing six lymphoma subtypes showed more than marginal expression of KDR or FLT4. Western blot analyses confirmed KDR and FLT4 protein expression in HDMECs, HUVECs and in cell lines with high VEGF-R mRNA levels. Mature VEGF-C induced p42/44 MAPK activation in the KDR- /FLT4+ cell line OCI-AML1 verifying the model character of this cell line for VEGF-C signal transduction studies. Bisulfite sequencing and MSP revealed that GpG islands in the promoter regions of KDR and FLT4 were unmethylated in HUVECs, HDMECs and KDR + and FLT4 + cell lines, whereas methylated cell lines did not express these genes. In hypermethylated cell lines, KDR and FLT4 were re-inducible by treatment with the DNA demethylating agent 5-Aza-2'deoxycytidine, confirming epigenetic regulation of both genes. Conclusions Our data show that VEGF-Rs KDR and FLT4 are silenced by DNA methylation. However, if the promoters are unmethylated, other factors (e.g. transactivation factors) determine the extent of KDR and FLT4 expression