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

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

Molecular Cytogenetic Analysis and Resequencing of Contactin Associated Protein-Like 2 in Autism Spectrum Disorders

Autism spectrum disorders (ASD) are a group of related neurodevelopmental syndromes with complex genetic etiology.1 We identified a de novo chromosome 7q inversion disrupting Autism susceptibility candidate 2 (AUTS2) and Contactin Associated Protein-Like 2 (CNTNAP2) in a child with cognitive and social delay. We focused our initial analysis on CNTNAP2 based on our demonstration of disruption of Contactin 4 (CNTN4) in a patient with ASD;2 the recent finding of rare homozygous mutations in CNTNAP2 leading to intractable seizures and autism;3 and in situ and biochemical analyses reported herein that confirm expression in relevant brain regions and demonstrate the presence of CNTNAP2 in the synaptic plasma membrane fraction of rat forebrain lysates. We comprehensively resequenced CNTNAP2 in 635 patients and 942 controls. Among patients, we identified a total of 27 nonsynonymous changes; 13 were rare and unique to patients and 8 of these were predicted to be deleterious by bioinformatic approaches and/or altered residues conserved across all species. One variant at a highly conserved position, I869T, was inherited by four affected children in three unrelated families, but was not found in 4010 control chromosomes (p = 0.014). Overall, this resequencing data demonstrated a modest nonsignificant increase in the burden of rare variants in cases versus controls. Nonethless, when viewed in light of two independent studies published in this issue of AJHG showing a relationship between ASD and common CNTNAP2 alleles,4,5 the cytogenetic and mutation screening data suggest that rare variants may also contribute to the pathophysiology of ASD, but place limits on the magnitude of this contribution