Constraining the growth rate by combining multiple future surveys

The growth rate of large-scale structure provides a powerful consistency test of the standard cosmological model and a probe of possible deviations from general relativity. We use a Fisher analysis to forecast constraints on the growth rate from a combination of next-generation spectroscopic surveys. In the overlap survey volumes, we use a multi-tracer analysis to significantly reduce the effect of cosmic variance. The non-overlap individual survey volumes are included in the Fisher analysis in order to utilise the entire volume. We use the observed angular power spectrum, which naturally includes all wide-angle and lensing effects and circumvents the need for an Alcock-Paczynski correction. Cross correlations between redshift bins are included by using a novel technique to avoid computation of the sub-dominant contributions. Marginalising over the standard cosmological parameters, as well as the clustering bias in each redshift bin, we find that the precision on γ improves on the best single-tracer precision by up to ∼50

Renal revascularization in Takayasu arteritis–induced renal artery stenosis

AbstractPurposeThis study was undertaken to define the long-term effects of renal revascularization on blood pressure, and renal and cardiac function in patients with Takayasu arteritis–induced renal artery stenosis (TARAS).MethodsTwenty-seven patients (25 women; mean age, 27 years) with TARAS underwent intervention. Primary, primary assisted, and secondary patency rates were determined, and the late effects on blood pressure, renal and cardiac function, and survival were analyzed.ResultsAll patients had hypertension (mean blood pressure, 167/99 mm Hg; 2.5 antihypertensive medications per patient). Mean estimated glomerular filtration rate in patients not receiving hemodialysis was 76 mL/min, and in five patients serum creatinine concentration was greater than 1.5 mg/dL. Three patients were hemodialysis-dependent, and two had intractable congestive heart failure. Forty interventions were performed, including 32 aortorenal bypass procedures, two repeat implantations, four nephrectomies, and two transluminal angioplasty procedures. Postoperative morbidity was 19%. There were no deaths. During follow-up (mean, 68 months), three graft stenoses, all due to intimal hyperplasia, and three graft occlusions occurred. Two of three graft stenoses were successfully revised. At 1, 3, and 5 years of follow-up, primary patency was 87%, 79%, and 79%, respectively; primary assisted patency was 93%, 89%, 89%, respectively; and secondary patency was 93%, 89%, and 89%, respectively. Intervention resulted in a decrease in blood pressure to a mean of 132/79 mm Hg (P < .0001), and the need for antihypertensive medications was reduced to one per patient (P < .01). Mean glomerular filtration rate increased to 88 mL/min (P < .005), and two patients no longer required hemodialysis. Congestive heart failure resolved in both patients, and did not recur. There were three deaths during follow-up, with 5-year and 10-year actuarial survival of 96% and 80%, respectively.ConclusionsRenal revascularization to treat TARAS is durable, has a salutary effect on blood pressure, and enhances long-term renal and cardiac function. This response establishes renal revascularization as a successful and durable intervention for TARAS, and a benchmark to which other therapies should be compared

High-level expression of biologically active glycoprotein hormones in Pichia pastoris strains—selection of strain GS115, and not X-33, for the production of biologically active N-glycosylated 15N-labeled phCG

The methylotrophic yeast Pichia pastoris is widely used for the production of recombinant glycoproteins. With the aim to generate biologically active 15N-labeled glycohormones for conformational studies focused on the unravelling of the NMR structures in solution, the P. pastoris strains GS115 and X-33 were explored for the expression of human chorionic gonadotropin (phCG) and human follicle-stimulating hormone (phFSH). In agreement with recent investigations on the N-glycosylation of phCG, produced in P. pastoris GS115, using ammonia/glycerol-methanol as nitrogen/carbon sources, the N-glycosylation pattern of phCG, synthesized using NH4Cl/glucose–glycerol–methanol, comprised neutral and charged, phosphorylated high-mannose-type N-glycans (Man8–15GlcNAc2). However, the changed culturing protocol led to much higher amounts of glycoprotein material, which is of importance for an economical realistic approach of the aimed NMR research. In the context of these studies, attention was also paid to the site specific N-glycosylation in phCG produced in P. pastoris GS115. In contrast to the rather simple N-glycosylation pattern of phCG expressed in the GS115 strain, phCG and phFSH expressed in the X-33 strain revealed, besides neutral high-mannose-type N-glycans, also high concentrations of neutral hypermannose-type N-glycans (Manup-to-30GlcNAc2). The latter finding made the X-33 strain not very suitable for generating 15N-labeled material. Therefore, 15N-phCG was expressed in the GS115 strain using the new optimized protocol. The 15N-enrichment was evaluated by 15N-HSQC NMR spectroscopy and GLC-EI/MS. Circular dichroism studies indicated that 15N-phCG/GS115 had the same folding as urinary hCG. Furthermore, 15N-phCG/GS115 was found to be similar to the unlabeled protein in every respect as judged by radioimmunoassay, radioreceptor assays, and in vitro bioassays

Reflecting on loss in Papua New Guinea

This article takes up the conundrum of conducting anthropological fieldwork with people who claim that they have 'lost their culture,' as is the case with Suau people in the Massim region of Papua New Guinea. But rather than claiming culture loss as a process of dispossession, Suau claim it as a consequence of their own attempts to engage with colonial interests. Suau appear to have responded to missionization and their close proximity to the colonial-era capital by jettisoning many of the practices characteristic of Massim societies, now identified as 'kastom.' The rejection of kastom in order to facilitate their relations with Europeans during colonialism, followed by the mourning for kastom after independence, both invite consideration of a kind of reflexivity that requires action based on the presumed perspective of another

Immunohistochemical Characterisation of GLUT1, MMP3 and NRF2 in Osteosarcoma.

Osteosarcoma (OSA) is an aggressive bone malignancy. Unlike many other malignancies, OSA outcomes have not improved in recent decades. One challenge to the development of better diagnostic and therapeutic methods for OSA has been the lack of well characterized experimental model systems. Spontaneous OSA in dogs provides a good model for the disease seen in people and also remains an important veterinary clinical challenge. We recently used RNA sequencing and qRT-PCR to provide a detailed molecular characterization of OSA relative to non-malignant bone in dogs. We identified differential mRNA expression of the solute carrier family 2 member 1 (SLC2A1/GLUT1), matrix metallopeptidase 3 (MMP3) and nuclear factor erythroid 2-related factor 2 (NFE2L2/NRF2) genes in canine OSA tissue in comparison to paired non-tumor tissue. Our present work characterizes protein expression of GLUT1, MMP3 and NRF2 using immunohistochemistry. As these proteins affect key processes such as Wnt activation, heme biosynthesis, glucose transport, understanding their expression and the enriched pathways and gene ontologies enables us to further understand the potential molecular pathways and mechanisms involved in OSA. This study further supports spontaneous OSA in dogs as a model system to inform the development of new methods to diagnose and treat OSA in both dogs and people

High-sensitivity high-resolution X-ray imaging with soft-sintered metal halide perovskites

To realize the potential of artificial intelligence in medical imaging, improvements in imaging capabilities are required, as well as advances in computing power and algorithms. Hybrid inorganic–organic metal halide perovskites, such as methylammonium lead triiodide (MAPbI3), offer strong X-ray absorption, high carrier mobilities (µ) and long carrier lifetimes (τ), and they are promising materials for use in X-ray imaging. However, their incorporation into pixelated sensing arrays remains challenging. Here we show that X-ray flat-panel detector arrays based on microcrystalline MAPbI3 can be created using a two-step manufacturing process. Our approach is based on the mechanical soft sintering of a freestanding absorber layer and the subsequent integration of this layer on a pixelated backplane. Freestanding microcrystalline MAPbI3 wafers exhibit a sensitivity of 9,300 µC Gyair–1 cm–2 with a μτ product of 4 × 10–4 cm2 V–1, and the resulting X-ray imaging detector, which has 508 pixels per inch, combines a high spatial resolution of 6 line pairs per millimetre with a low detection limit of 0.22 nGyair per frame

Migration patterns of Greenland halibut in the North Atlantic revealed by a compiled mark-recapture dataset

Marine fisheries are often allocated to stocks that reflect pragmatic considerations and may not represent the species’ spatial population structure, increasing the risk of mismanagement and unsustainable harvesting. Here we compile mark–recapture data collected across the North Atlantic to gain insight into the spatial population structure of Greenland halibut (Reinhardtius hippoglossoides), an issue that has been unresolved for decades. The dataset contains 168130 fish tagged from 1952 to 2021, with 5466 (3.3%) recaptured individuals. Our results indicate that fish tagged at <50 cm body length migrate at higher rates, suggesting that mark–recapture studies on adult individuals underestimate population-level migration rates. We find evidence for migrations across management units in the North Atlantic indicating two regional offshore populations: one in the Northeast Atlantic, where the West Nordic and Northeast Arctic stocks, currently managed separately, likely belong to a single population that spans from the Kara Sea to Southeast Greenland; and one in the Northwest Atlantic where migration was observed between the Newfoundland and Labrador stock and the Northwest Arctic stock in Davis Strait and Baffin Bay. Our findings indicate complex population structure with implications for international and domestic fisheries management of this long-lived species.publishedVersio

Detection of regulator genes and eQTLs in gene networks

Genetic differences between individuals associated to quantitative phenotypic traits, including disease states, are usually found in non-coding genomic regions. These genetic variants are often also associated to differences in expression levels of nearby genes (they are "expression quantitative trait loci" or eQTLs for short) and presumably play a gene regulatory role, affecting the status of molecular networks of interacting genes, proteins and metabolites. Computational systems biology approaches to reconstruct causal gene networks from large-scale omics data have therefore become essential to understand the structure of networks controlled by eQTLs together with other regulatory genes, and to generate detailed hypotheses about the molecular mechanisms that lead from genotype to phenotype. Here we review the main analytical methods and softwares to identify eQTLs and their associated genes, to reconstruct co-expression networks and modules, to reconstruct causal Bayesian gene and module networks, and to validate predicted networks in silico.Comment: minor revision with typos corrected; review article; 24 pages, 2 figure