Analysis of 13 C and 14 C labeling in pyruvate and lactate in tumor and blood of lymphoma-bearing mice injected with 13 C- and 14 C-labeled pyruvate

Measurements of hyperpolarized 13C label exchange between injected [1‐13C]pyruvate and the endogenous tumor lactate pool can give an apparent first‐order rate constant for the exchange. The determination of the isotope flux, however, requires an estimate of the labeled pyruvate concentration in the tumor. This was achieved here by measurement of the tumor uptake of [1‐14C]pyruvate, which showed that <2% of the injected pyruvate reached the tumor site. Multiplication of this estimated labeled pyruvate concentration in the tumor with the apparent first‐order rate constant for hyperpolarized 13C label exchange gave an isotope flux that showed good agreement with a flux determined directly by the injection of non‐polarized [3‐13C]pyruvate, rapid excision of the tumor after 30 s and measurement of 13C‐labeled lactate concentrations in tumor extracts. The distribution of labeled lactate between intra‐ and extracellular compartments and the blood pool was investigated by imaging, by measurement of the labeled lactate concentration in blood and tumor, and by examination of the effects of a gadolinium contrast agent and a lactate transport inhibitor on the intensity of the hyperpolarized [1‐13C]lactate signal. These measurements showed that there was significant export of labeled lactate from the tumor, but that labeled lactate in the blood pool produced by the injection of hyperpolarized [1‐13C]pyruvate showed only relatively low levels of polarization. This study shows that measurements of hyperpolarized 13C label exchange between pyruvate and lactate in a murine tumor model can provide an estimate of the true isotope flux if the concentration of labeled pyruvate that reaches the tumor can be determined

Automated Coronal Hole Detection using Local Intensity Thresholding Techniques

We identify coronal holes using a histogram-based intensity thresholding technique and compare their properties to fast solar wind streams at three different points in the heliosphere. The thresholding technique was tested on EUV and X-ray images obtained using instruments onboard STEREO, SOHO and Hinode. The full-disk images were transformed into Lambert equal-area projection maps and partitioned into a series of overlapping sub-images from which local histograms were extracted. The histograms were used to determine the threshold for the low intensity regions, which were then classified as coronal holes or filaments using magnetograms from the SOHO/MDI. For all three instruments, the local thresholding algorithm was found to successfully determine coronal hole boundaries in a consistent manner. Coronal hole properties extracted using the segmentation algorithm were then compared with in situ measurements of the solar wind at 1 AU from ACE and STEREO. Our results indicate that flux tubes rooted in coronal holes expand super-radially within 1 AU and that larger (smaller) coronal holes result in longer (shorter) duration high-speed solar wind streams

Restoring habitat for fire-impacted species' across degraded Australian landscapes

In the summer of 2019-2020, southern Australia experienced the largest fires on record, detrimentally impacting the habitat of native species, many of which were already threatened by past and current anthropogenic land use. A large-scale restoration effort to improve degraded species habitat would provide fire-affected species with the chance to recover and persist in burnt and unburnt habitat. To facilitate this, decision-makers require information on priority species needs for restoration intervention, the suite of potential restoration interventions, and the priority locations for applying these interventions. We prioritize actions in areas where restoration would most likely provide cost-effective benefits to priority species (defined by each species proportion of habitat burned, threat status, and vulnerability to fires), by integrating current and future species habitat suitability maps with spatially modelled costs of restoration interventions such as replanting, removing invasive species, and implementing ecologically appropriate fire management. We show that restoring the top similar to 69% (112 million hectares) of the study region (current and future distributions of priority species) accounts for, on average, 95% of current and future habitat for every priority species and costs similar to AUD$73 billion yr(-1) (AUD$650 hectare(-1) yr(-1)) annualized over 30 years. This effort would include restoration actions over 6 million hectares of fire-impacted habitat, costing similar to AUD$8.8 billion/year. Large scale restoration efforts are often costly but can have significant societal co-benefits beyond biodiversity conservation. We also show that up to 291 MtCO2 (similar to 150 Mt DM) of carbon could be sequestered by restoration efforts, resulting in approximately AUD$253 million yr(-1) in carbon market revenue if all carbon was remunerated. Our approach highlights the scale, costs, and benefits of targeted restoration activities both inside and outside of the immediate bushfire footprint over vast areas of different land tenures

Restoring habitat for fire-impacted species’ across degraded Australian landscapes

In the summer of 2019–2020, southern Australia experienced the largest fires on record, detrimentally impacting the habitat of native species, many of which were already threatened by past and current anthropogenic land use. A large-scale restoration effort to improve degraded species habitat would provide fire-affected species with the chance to recover and persist in burnt and unburnt habitat. To facilitate this, decision-makers require information on priority species needs for restoration intervention, the suite of potential restoration interventions, and the priority locations for applying these interventions. We prioritize actions in areas where restoration would most likely provide cost-effective benefits to priority species (defined by each species proportion of habitat burned, threat status, and vulnerability to fires), by integrating current and future species habitat suitability maps with spatially modelled costs of restoration interventions such as replanting, removing invasive species, and implementing ecologically appropriate fire management. We show that restoring the top ∼69% (112 million hectares) of the study region (current and future distributions of priority species) accounts for, on average, 95% of current and future habitat for every priority species and costs ∼AUD$73 billion yr−1 (AUD$650 hectare−1 yr−1 ) annualized over 30 years. This effort would include restoration actions over 6 million hectares of fire-impacted habitat, costing ∼AUD$8.8 billion/year. Large scale restoration efforts are often costly but can have significant societal co-benefits beyond biodiversity conservation. We also show that up to 291 MtCO2 (∼150 Mt DM) of carbon could be sequestered by restoration efforts, resulting in approximately AUD$253 million yr−1 in carbon market revenue if all carbon was remunerated. Our approach highlights the scale, costs, and benefits of targeted restoration activities both inside and outside of the immediate bushfire footprint over vast areas of different land tenures.Michelle Ward, Ayesha Tulloch, Romola Stewart, Hugh P Possingham, Sarah Legge, Rachael V Gallagher, Erin M Graham, Darren Southwell, David Keith, Kingsley Dixon, Chuanji Yong, Josie Carwardine, Tim Cronin, April E Reside, and James E M Watso

Active Galactic Nuclei at the Crossroads of Astrophysics

Over the last five decades, AGN studies have produced a number of spectacular examples of synergies and multifaceted approaches in astrophysics. The field of AGN research now spans the entire spectral range and covers more than twelve orders of magnitude in the spatial and temporal domains. The next generation of astrophysical facilities will open up new possibilities for AGN studies, especially in the areas of high-resolution and high-fidelity imaging and spectroscopy of nuclear regions in the X-ray, optical, and radio bands. These studies will address in detail a number of critical issues in AGN research such as processes in the immediate vicinity of supermassive black holes, physical conditions of broad-line and narrow-line regions, formation and evolution of accretion disks and relativistic outflows, and the connection between nuclear activity and galaxy evolution.Comment: 16 pages, 5 figures; review contribution; "Exploring the Cosmic Frontier: Astrophysical Instruments for the 21st Century", ESO Astrophysical Symposia Serie

Just a guy in pajamas? Framing the blogs in mainstream US newspaper coverage (1999—2005)

When new technologies are introduced to the public, their widespread adoption is dependent, in part, on news coverage (Rogers, 1995).Yet, as weblogs began to play major role in the public spheres of politics and journalism, journalists faced a paradox: how to cover a social phenomenon that was too large to ignore and posed a significant threat to their profession. This article examines how blogs were framed by US newspapers as the public became more aware of the blogging world. A content analysis of blog-related stories in major US newspapers from 1999 to 2005 was conducted. Findings suggest that newspaper coverage framed blogs as more beneficial to individuals and small cohorts than to larger social entities such as politics, business and journalism. Moreover, only in the realm of journalism were blogs framed as more of a threat than a benefit, and rarely were blogs considered an actual form of journalism.Yeshttps://us.sagepub.com/en-us/nam/manuscript-submission-guideline

The impact of the metabotropic glutamate receptor and other gene family interaction networks on autism

Although multiple reports show that defective genetic networks underlie the aetiology of autism, few have translated into pharmacotherapeutic opportunities. Since drugs compete with endogenous small molecules for protein binding, many successful drugs target large gene families with multiple drug binding sites. Here we search for defective gene family interaction networks (GFINs) in 6,742 patients with the ASDs relative to 12,544 neurologically normal controls, to find potentially druggable genetic targets. We find significant enrichment of structural defects (P≤2.40E-09, 1.8-fold enrichment) in the metabotropic glutamate receptor (GRM) GFIN, previously observed to impact attention deficit hyperactivity disorder (ADHD) and schizophrenia. Also, the MXD-MYC-MAX network of genes, previously implicated in cancer, is significantly enriched (P≤3.83E-23, 2.5-fold enrichment), as is the calmodulin 1 (CALM1) gene interaction network (P≤4.16E-04, 14.4-fold enrichment), which regulates voltage-independent calcium-activated action potentials at the neuronal synapse. We find that multiple defective gene family interactions underlie autism, presenting new translational opportunities to explore for therapeutic interventions