John Hainsworth Mercer, 1922-1987

From 1951 until 1954, Mercer studied at McGill University. His Ph.D. thesis, ... was based on field work carried out in the vicinity of the Grinnell and Terra Nivea ice caps on southern Baffin Island. ... Mercer was highly motivated by field work and literally thrived on it. Typically, and often to the chagrin of at least one of his contemporaries, Mercer did not unnecessarily burden himself (or others) with loads of data. Many of his papers seemed to be largely based on his unusual synthesizing and perceptive powers, supported, where necessary, by a few, but key, radioisotope dates. Mercer was not a compulsive lecturer - in fact, he shunned such "duties" - but for those of us at the institute as graduate students (of which G.H. was one) Mercer was frequently a source of both private inspiration and considerable amusement. An important paper in 1968 set in motion his and others' ideas on the dynamics of "marine ice sheets" (Mercer, 1968). ... His realistic thinking through the ice sheet dynamics scenarios and the associated sea level changes inspired the numerical modellers to dedicate their paper to him. ... The results of his field work are of great importance in synthesizing the spatial variations of global climate change, which was one of the underlying themes of Mercer's research. ... His stimulating presence will be widely missed, especially by those at the Byrd Polar Research Center in Columbus, Ohio

An Intervention Model For Homeless Youth

Youth homelessness has become a more visible problem in recent years, and is exacerbated by changes in the central city economy, schooling, and the family. This article describes the Street Youth Employment Program, a program designed by sociological practitioners to intervene into the lives of homeless street youth through a collaborative effort between a socio-medical clink and an urban university. Program elements included (1) Stabilizing the living conditions of homeless youth, (2) Providing immediate part-time employment for participants on subsidized work projects, (3) Ensuring participation by youth in program policy and operation, and (4) Providing education and on-the-job training for youth. Of the youth who participated in the program (N = 16), the majority (70%) successfully moved away from living on the street to more stable involvement in work or school. The limited success of the intervention was attributed primarily to the linkage of meaningful employment with stable living arrangements, and attention to medical and mental health needs. It was noted that direct job creation is a more appropriate intervention strategy for homeless youth man pre-employment and job readiness services alone

Correspondence About Chucalissa Corn

A series of letters from the late 1960s regarding research performed on corn samples taken in excavation at Chucalissa

An Evaluation of Columbia Villa/Tamaracks Community Service Intervention Project

The Community Service Intervention Program (CSlP) is a unique public agency response to a multifaceted set of problems confronting low income residents living in Oregon \u27s largest public housing project. The primary goals of the CSIP are to reduce crime, reduce the fear of crime among residents, and to improve the quality of life of the families living in Columbia Villa/Tamaracks. The evaluation of the CSIP combined a number of different research methods, on different analytical levels, to provide a summary assessment. Data were collected from individuals, from agencies, and from police records in a post facto analysis of the CSIP. Recommendations include: a higher profile by the County to coordinate, plan, manage, and evaluate services according to a set of carefully chosen set of objectives; a longitudinal evaluation of CSIP efforts; greater involvement by Columbia Villa/Tamaracks residents; greater job opportunities and job training for Columbia Villa/Tamaracks residents; additional participation in the CSIP by the Fire Department, Tri-Met, Metro (Solid Waste), and DEQ

Targeting of Histone Acetyltransferase p300 by Cyclopentenone Prostaglandin Δ12-PGJ2 through Covalent Binding to Cys1438

This document is the Accepted Manuscript version of a Published Work that appeared in final form in Chemical Research in Toxicology, copyright © American Chemical Society after peer review and technical editing by the publisher. To access the final edited and published work see http://pubs.acs.org/doi/abs/10.1021/tx200383cInhibitors of histone acetyltransferases (HATs) are perceived to treat diseases like cancer, neurodegeneration, and AIDS. On the basis of previous studies, we hypothesized that Cys1438 in the substrate binding site could be targeted by Δ12-prostaglandin J2 (Δ12-PGJ2), a cyclopentenone prostaglandin (CyPG) derived from PGD2. We demonstrate here the ability of CyPGs to inhibit p300 HAT-dependent acetylation of histone H3. A cell-based assay system clearly showed that the α,β-unsaturation in the cyclopentenone ring of Δ12-PGJ2 was crucial for the inhibitory activity, while the 9,10-dihydro-15-deoxy- Δ12,14-PGJ2, which lacks the electrophilic carbon (at carbon 9), was ineffective. Molecular docking studies suggested that Δ12-PGJ2 places the electrophilic carbon in the cyclopentenone ring well within the vicinity of Cys1438 of p300 to form a covalent Michael adduct. Site-directed mutagenesis of the p300 HAT domain, peptide competition assay involving p300 wild type and mutant peptides, followed by mass spectrometric analysis confirmed the covalent interaction of Δ12-PGJ2 with Cys1438. Using biotinylated derivatives of Δ12-PGJ2 and 9,10-dihydro-15-deoxy- Δ12,14-PGJ2, we demonstrate the covalent interaction of Δ12-PGJ2 with the p300 HAT domain, but not the latter. In agreement with the in vitro filter binding assay, CyPGs were also found to inhibit H3 histone acetylation in cell-based assays. In addition, Δ12-PGJ2 also inhibited the acetylation of the HIV-1 Tat by recombinant p300 in in vitro assays. This study demonstrates, for the first time, that Δ12-PGJ2 inhibits p300 through Michael addition, where α,β-unsaturated carbonyl function is absolutely required for the inhibitory activity

In Pursuit of Prehistoric Caribou on Thandlät, Southern Yukon

In 1997, the first author noted a large concentration of caribou (Rangifer sp.) fecal pellets and a caribou antler on a permanent snow patch in the Kusawa Lake area of southern Yukon. Caribou are completely absent from this area today. Coring of the snow patch revealed continuous deposits of fecal pellets to depths of at least 160 cm. The proximal portion of a wooden dart or arrow shaft fragment recovered on the edge of the snow patch represents one of the few organic examples of mid-Holocene hunting technology ever found in Canada. An age of 2450 BP ± 50 years was obtained for the fecal material from approximately 1.6 m below the surface of the snow patch, and the dart was dated at 4360 BP ± 50 years. These dates indicate that aboriginal Yukon hunters have been harvesting caribou at this location for at least 4000 years. The Thandlät site offers a rare opportunity to explore a number of questions regarding the prehistoric ecology of large caribou populations, the implications of climate change for caribou populations, and human use of high-elevation hunting sites.En 1997, le premier auteur a découvert une concentration élevée de boulettes fécales (Rangifer sp.) et des bois de caribou sur une congère dans la région du lac Kusawa, dans le sud du Yukon. Il n'y a plus de caribous dans cette région. Le carottage de la congère a révélé des dépôts de boulettes jusqu'à une profondeur de 160 cm. Un fragment de dard ou de la flèche en bois trouvé sur le bord de la congère représente une des rares découvertes au Canada relatives à ce type d'arme. Il a été déterminé que les matières fécales prélevées dans la congère, à environ 1,6 m de profondeur, sont âgées de 2450 BP ± 50 ans, et que le dard aurait 4360 BP ± 50 ans. Ces dates montrent que les Autochtones du Yukon chassaient déjà le caribou à cet endroit il y a 4000 ans. Le site Thandlät est un des rares endroits où l'on peut observer divers aspects préhistoriques des grandes populations de caribou, des effets des changements climatiques sur les populations de caribous et des activités de chasse à grande altitude

Restoring Ureagenesis in Hepatocytes by CRISPR/Cas9-mediated Genomic Addition to Arginase-deficient Induced Pluripotent Stem Cells.

Urea cycle disorders are incurable enzymopathies that affect nitrogen metabolism and typically lead to hyperammonemia. Arginase deficiency results from a mutation in Arg1, the enzyme regulating the final step of ureagenesis and typically results in developmental disabilities, seizures, spastic diplegia, and sometimes death. Current medical treatments for urea cycle disorders are only marginally effective, and for proximal disorders, liver transplantation is effective but limited by graft availability. Advances in human induced pluripotent stem cell research has allowed for the genetic modification of stem cells for potential cellular replacement therapies. In this study, we demonstrate a universally-applicable CRISPR/Cas9-based strategy utilizing exon 1 of the hypoxanthine-guanine phosphoribosyltransferase locus to genetically modify and restore arginase activity, and thus ureagenesis, in genetically distinct patient-specific human induced pluripotent stem cells and hepatocyte-like derivatives. Successful strategies restoring gene function in patient-specific human induced pluripotent stem cells may advance applications of genetically modified cell therapy to treat urea cycle and other inborn errors of metabolism

Multicenter Evaluation of the Portrait Staph ID/R Blood Culture Panel for Rapid Identification of Staphylococci and Detection of the mecA Gene

Bloodstream infections are a leading cause of morbidity and mortality in the United States and are associated with increased health care costs. We evaluated the Portrait Staph ID/R blood culture panel (BCP) multiplex PCR assay (Great Basin Scientific, Salt Lake City, UT) for the rapid and simultaneous identification (ID) of Staphylococcus aureus, Staphylococcus lugdunensis, and Staphylococcus species to the genus level and the detection of the mecA gene directly from a positive blood culture bottle. A total of 765 Bactec bottles demonstrating Gram-positive cocci in singles or clusters were tested during the prospective trial at 3 clinical sites. The Portrait Staph ID/R BCP results were compared with results from conventional biochemical and cefoxitin disk methods performed at an independent laboratory. Discordant ID and mecA results were resolved by rpoB gene sequencing and mecA gene sequencing, respectively. A total of 658 Staphylococcus species isolates (S. aureus, 211 isolates; S. lugdunensis, 3 isolates; and Staphylococcus spp., 444 isolates) were recovered from monomicrobial and 33 polymicrobial blood cultures. After discrepant analysis, the overall ratios of Portrait Staph ID/R BCP positive percent agreement and negative percent agreement were 99.4%/99.9% for Staphylococcus ID and 99.7%/99.2% for mecA detection