Preliminary Results for the Extraction and Measurement of Cosmogenic in Situ 14

From the 18th International Radiocarbon Conference held in Wellington, New Zealand, September 1-5, 2003.Radiocarbon is produced within minerals at the earth's surface (in situ production) by a number of spallation reactions. Its relatively short half-life of 5730 yr provides us with a unique cosmogenic nuclide tool for the measurement of rapid erosion rates (>10^-3 cm yr-1) and events occurring over the past 25 kyr. At SUERC, we have designed and built a vacuum system to extract 14C from quartz which is based on a system developed at the University of Arizona. This system uses resistance heating of samples to a temperature of approximately 1100 degrees C in the presence of lithium metaborate (LiBO2) to dissolve the quartz and liberate any carbon present. During extraction, the carbon is oxidized to CO2 in an O2atmosphere so that it may be collected cryogenically. The CO2 is subsequently purified and converted to graphite for accelerator mass spectrometry (AMS) measurement. One of the biggest problems in measuring in situ 14C is establishing a low and reproducible system blank and efficient extraction of the in situ 14C component. Here, we present initial data for 14C-free CO2, derived from geological carbonate and added to the vacuum system to determine the system blank. Shielded quartz samples (which should be 14C free) and a surface quartz sample routinely analyzed at the University of Arizona were also analyzed at SUERC, and the data compared with values derived from the University of Arizona system.The Radiocarbon archives are made available by Radiocarbon and the University of Arizona Libraries. Contact [email protected] for further information.Migrated from OJS platform February 202

Family Ties and Child Placement

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/73323/1/j.1545-5300.1978.00289.x.pd

Low-level APC mutational mosaicism is the underlying cause in a substantial fraction of unexplained colorectal adenomatous polyposis cases

BACKGROUND: In 30-50% of patients with colorectal adenomatous polyposis, no germline mutation in the known genes APC, causing familial adenomatous polyposis, MUTYH, causing MUTYH-associated polyposis, or POLE or POLD1, causing polymerase-proofreading-associated polyposis can be identified, although a hereditary aetiology is likely. This study aimed to explore the impact of APC mutational mosaicism in unexplained polyposis. METHODS: To comprehensively screen for somatic low-level APC mosaicism, high-coverage next-generation sequencing of the APC gene was performed using DNA from leucocytes and a total of 53 colorectal tumours from 20 unrelated patients with unexplained sporadic adenomatous polyposis. APC mosaicism was assumed if the same loss-of-function APC mutation was present in ≥2 anatomically separated colorectal adenomas/carcinomas per patient. All mutations were validated using diverse methods. RESULTS: In 25% (5/20) of patients, somatic mosaicism of a pathogenic APC mutation was identified as underlying cause of the disease. In 2/5 cases, the mosaic level in leucocyte DNA was slightly below the sensitivity threshold of Sanger sequencing; while in 3/5 cases, the allelic fraction was either very low (0.1-1%) or no mutations were detectable. The majority of mosaic mutations were located outside the somatic mutation cluster region of the gene. CONCLUSIONS: The present data indicate a high prevalence of pathogenic mosaic APC mutations below the detection thresholds of routine diagnostics in adenomatous polyposis, even if high-coverage sequencing of leucocyte DNA alone is taken into account. This has important implications for both routine work-up and strategies to identify new causative genes in this patient group

Shifting patterns of genomic variation in the somatic evolution of papillary thyroid carcinoma

Shows Single Nucleotide Substitutions in the MAPK Pathway. (XLSX 43 kb

Ice surface changes during recent glacial cycles along the Jutulstraumen and Penck Trough ice streams in western Dronning Maud Land, East Antarctica

Reconstructing past ice-sheet surface changes is key to testing and improving ice-sheet models. Data constraining the past behaviour of the East Antarctic Ice Sheet are sparse, limiting our understanding of its response to past, present and future climate change. Here, we report the first cosmogenic multi-nuclide (10Be, 26Al, 36Cl) data from bedrock and erratics on nunataks along the Jutulstraumen and Penck Trough ice streams in western Dronning Maud Land, East Antarctica. Spanning elevations between 741 and 2394 m above sea level, the samples have apparent exposure ages between 2 ka and 5 Ma. The highest-elevation bedrock sample indicates (near-) continuous minimum exposure since the Pliocene, with a low apparent erosion rate of 0.15 ± 0.03 m Ma−1, which is similar to results from eastern Dronning Maud Land. In contrast to studies in eastern Dronning Maud Land, however, our data show clear indications of a thicker-than-present ice sheet within the last glacial cycle, with a thinning of ∼35–120 m during the Holocene (∼2–11 ka). Difficulties in separating suitable amounts of quartz from the often quartz-poor rock-types in the area, and cosmogenic nuclides inherited from exposure prior to the last deglaciation, prevented robust thinning estimates from elevational profiles. Nevertheless, the results clearly demonstrate ice-surface fluctuations of several hundred meters between the current grounding line and the edge of the polar plateau for the last glacial cycle, a constraint that should be considered in future ice-sheet model simulations

Reiterated Commemoration: Hiroshima as National Trauma *

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/75748/1/j.1467-9558.2006.00295.x.pd

Low-level APC mutational mosaicism is the underlying cause in a substantial fraction of unexplained colorectal adenomatous polyposis cases

Background In 30-50% of patients with colorectal adenomatous polyposis, no germline mutation in the known genes APC, causing familial adenomatous polyposis, MUTYH, causing MUTYH-associated polyposis, or POLE or POLD1, causing polymerase-proofreading-associated polyposis can be identified, although a hereditary aetiology is likely. This study aimed to explore the impact of APC mutational mosaicism in unexplained polyposis. Methods To comprehensively screen for somatic low-level APC mosaicism, high-coverage next-generation sequencing of the APC gene was performed using DNA from leucocytes and a total of 53 colorectal tumours from 20 unrelated patients with unexplained sporadic adenomatous polyposis. APC mosaicism was assumed if the same loss-of-function APC mutation was present in 2 anatomically separated colorectal adenomas/carcinomas per patient. All mutations were validated using diverse methods. Results In 25% (5/20) of patients, somatic mosaicism of a pathogenic APC mutation was identified as underlying cause of the disease. In 2/5 cases, the mosaic level in leucocyte DNA was slightly below the sensitivity threshold of Sanger sequencing;while in 3/5 cases, the allelic fraction was either very low (0.1-1%) or no mutations were detectable. The majority of mosaic mutations were located outside the somatic mutation cluster region of the gene. Conclusions The present data indicate a high prevalence of pathogenic mosaic APC mutations below the detection thresholds of routine diagnostics in adenomatous polyposis, even if high-coverage sequencing of leucocyte DNA alone is taken into account. This has important implications for both routine work-up and strategies to identify new causative genes in this patient group

Rare deleterious mutations of the gene EFR3A in autism spectrum disorders

Background: Whole-exome sequencing studies in autism spectrum disorder (ASD) have identified de novo mutations in novel candidate genes, including the synaptic gene Eighty-five Requiring 3A (EFR3A). EFR3A is a critical component of a protein complex required for the synthesis of the phosphoinositide PtdIns4P, which has a variety of functions at the neural synapse. We hypothesized that deleterious mutations in EFR3A would be significantly associated with ASD. Methods: We conducted a large case/control association study by deep resequencing and analysis of whole-exome data for coding and splice site variants in EFR3A. We determined the potential impact of these variants on protein structure and function by a variety of conservation measures and analysis of the Saccharomyces cerevisiae Efr3 crystal structure. We also analyzed the expression pattern of EFR3A in human brain tissue. Results: Rare nonsynonymous mutations in EFR3A were more common among cases (16 / 2,196 = 0.73%) than matched controls (12 / 3,389 = 0.35%) and were statistically more common at conserved nucleotides based on an experiment-wide significance threshold (P = 0.0077, permutation test). Crystal structure analysis revealed that mutations likely to be deleterious were also statistically more common in cases than controls (P = 0.017, Fisher exact test). Furthermore, EFR3A is expressed in cortical neurons, including pyramidal neurons, during human fetal brain development in a pattern consistent with ASD-related genes, and it is strongly co-expressed (P < 2.2 × 10−16, Wilcoxon test) with a module of genes significantly associated with ASD. Conclusions: Rare deleterious mutations in EFR3A were found to be associated with ASD using an experiment-wide significance threshold. Synaptic phosphoinositide metabolism has been strongly implicated in syndromic forms of ASD. These data for EFR3A strengthen the evidence for the involvement of this pathway in idiopathic autism

Natural law, non-voluntary euthanasia, and public policy

© 2019 by Emerald Publishing Limited. Natural Law philosophy asserts that there are universally binding and universally evident principles that can be determined to guide the actions of persons. Moreover, many of these principles have been enshrined in both statute and common law, thus ensuring their saliency for staff and institutions charged with palliative care. The authors examine the often emotive and politicized matter of (non-voluntary) euthanasia – acts or omissions made with the intent of causing or hastening death – with reference to Natural Law philosophy. This leads us to propose a number of important public policy remedies to ensure dignity in dying for the patient, and their associates