Further Evidence for Chemical Fractionation from Ultraviolet Observations of Carbon Monoxide

Ultraviolet absorption from interstellar 12CO and 13CO was detected toward rho Oph A and chi Oph. The measurements were obtained at medium resolution with the Goddard High Resolution Spectrograph on the Hubble Space Telescope. Column density ratios, N(12CO)/N(13CO), of 125 \pm 23 and 117 \pm 35 were derived for the sight lines toward rho Oph A and chi Oph, respectively. A value of 1100 \pm 600 for the ratio N(12C16O)/N(12C18O) toward rho Oph A was also obtained. Absorption from vibrationally excited H_2 (v" = 3) was clearly seen toward this star as well. The ratios are larger than the isotopic ratios for carbon and oxygen appropriate for ambient interstellar material. Since for both carbon and oxygen the more abundant isotopomer is enhanced, selective isotopic photodissociation plays the key role in the fractionation process for these directions. The enhancement arises because the more abundant isotopomer has lines that are more optically thick, resulting in more self shielding from dissociating radiation. A simple argument involving the amount of self shielding [from N(12CO)] and the strength of the ultraviolet radiation field premeating the gas (from the amount of vibrationally excited H_2) shows that selective isotopic photodissociation controls the fractionation seen in these two sight lines, as well as the sight line to zeta Oph.Comment: 40 pages, 8 figures, to appear in 10 July 2003 issue of Ap

The practice of 'doing' evaluation: Lessons learned from nine complex intervention trials in action

Background: There is increasing recognition among trialists of the challenges in understanding how particular 'real-life' contexts influence the delivery and receipt of complex health interventions. Evaluations of interventions to change health worker and/or patient behaviours in health service settings exemplify these challenges. When interpreting evaluation data, deviation from intended intervention implementation is accounted for through process evaluations of fidelity, reach, and intensity. However, no such systematic approach has been proposed to account for the way evaluation activities may deviate in practice from assumptions made when data are interpreted.Methods: A collective case study was conducted to explore experiences of undertaking evaluation activities in the real-life contexts of nine complex intervention trials seeking to improve appropriate diagnosis and treatment of malaria in varied health service settings. Multiple sources of data were used, including in-depth interviews with investigators, participant-observation of studies, and rounds of discussion and reflection.Results and discussion: From our experiences of the realities of conducting these evaluations, we identified six key 'lessons learned' about ways to become aware of and manage aspects of the fabric of trials involving the interface of researchers, fieldworkers, participants and data collection tools that may affect the intended production of data and interpretation of findings. These lessons included: foster a shared understanding across the study team of how individual practices contribute to the study goals; promote and facilitate within-team communications for ongoing reflection on the progress of the evaluation; establish processes for ongoing collaboration and dialogue between sub-study teams; the importance of a field research coordinator bridging everyday project management with scientific oversight; collect and review reflective field notes on the progress of the evaluation to aid interpretation of outcomes; and these approaches should help the identification of and reflection on possible overlaps between the evaluation and intervention.Conclusion: The lessons we have drawn point to the principle of reflexivity that, we argue, needs to become part of standard practice in the conduct of evaluations of complex interventions to promote more meaningful interpretations of the effects of an intervention and to better inform future implementation and decision-making. © 2014 Reynolds et al.; licensee BioMed Central Ltd

Coarse-grained modeling study of nonpeptide RGD ligand density and PEG molecular weight on the conformation of poly(γ-glutamyl-glutamate) paclitaxel conjugates

Molecular shape, flexibility, and surface hydrophilicity are thought to influence the ability of nanoparticles to cross biological barriers during drug delivery. In this study, coarse-grained (CG) molecular dynamics (MD) simulations were used to study these properties of a polymer-drug construct in potential clinical development: poly(γ-glutamyl-glutamate)-paclitaxel-poly(ethylene glycol) nonpeptide RGD (PGG-PTX-PEG-npRGD), a linear glutamyl-glutamate polymer with paclitaxel and poly(ethylene glycol)-nonpeptide RGD side groups. It was hypothesized that the PEG molecular weight (MW) (500 Da; 1,000 Da; and 2,000 Da) and nonpeptide RGD ligand density (4, 8, 12, and 16 per molecule), respectively, may have advantageous effects on the shape, flexibility, and surface hydrophilicity of PGG-PTX-PEG-npRGD. Circular dichroism spectroscopy was used to suggest initial structures for the all-atom (AA) models of PGG-PTX-PEG-npRGD, which were further converted to CG models using a commercially available mapping algorithm. Due to its semi-flexibility, PGG-PTX-PEG-npRGD is not limited to one specific conformation. Thus, CG MD simulations were run until statistical equilibrium, at which PGG-PTX-PEG-npRGD is represented as an ensemble of statistically similar conformations. The size of a PGG-PTX-PEG-npRGD molecule is not affected by the PEG MW or the nonpeptide RGD density, but higher PEG MW results in increased surface density of a PGG-PTX-PEG-npRGD molecule. Most PGG-PTX-PEG-npRGD shapes are globular, although filamentous shapes were also observed in the PEG500 and PEG1000 molecules. PEG500 and PEG1000 molecules are more flexible than PEG2000 systems. A higher presence of npRGD ligands results in decrease surface hydrophilicity of PGG-PTX-PEG-npRGD. These results indicate that the PGG-PTX-PEG1000-npRGD4 and PGG-PTX-PEG1000-npRGD8 molecules are the most efficacious candidates and are further recommended for experimental preclinical studies

The social dimension of globalization: A review of the literature

With globalization affecting so many inter-connected areas, it is difficult to grasp its full impact. This literature review of over 120 sources considers the impact of globalization on wages and taxes, poverty, inequality, insecurity, child labour, gender, and migration. Opening with some stylized facts concerning globalization in 1985-2002, the authors then highlight recent findings on these areas, reporting on controversies and on emerging consensus where it exists. There follows a review of national and international policy responses designed to make globalization more sustainable and equitable and to deliver decent jobs, security and a voice in decision-making

Global human footprint on the linkage between biodiversity and ecosystem functioning in reef fishes

Copyright: © 2011 Mora et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.Difficulties in scaling up theoretical and experimental results have raised controversy over the consequences of biodiversity loss for the functioning of natural ecosystems. Using a global survey of reef fish assemblages, we show that in contrast to previous theoretical and experimental studies, ecosystem functioning (as measured by standing biomass) scales in a non-saturating manner with biodiversity (as measured by species and functional richness) in this ecosystem. Our field study also shows a significant and negative interaction between human population density and biodiversity on ecosystem functioning (i.e., for the same human density there were larger reductions in standing biomass at more diverse reefs). Human effects were found to be related to fishing, coastal development, and land use stressors, and currently affect over 75% of the world's coral reefs. Our results indicate that the consequences of biodiversity loss in coral reefs have been considerably underestimated based on existing knowledge and that reef fish assemblages, particularly the most diverse, are greatly vulnerable to the expansion and intensity of anthropogenic stressors in coastal areas

Geographic Life History Differences Predict Genomic Divergence Better than Mitochondrial Barcodes or Phenotype

Species diversity can be inferred using multiple data types, however, results based on genetic data can be at odds with patterns of phenotypic variation. Tiger beetles of the Cicindelidia politula (LeConte, 1875) species complex have been taxonomically problematic due to extreme phenotypic variation within and between populations. To better understand the biology and taxonomy of this group, we used mtDNA genealogies and multilocus nuclear analyses of 34,921 SNPs to elucidate its evolutionary history and evaluate the validity of phenotypically circumscribed species and subspecies. Genetic analyses recovered two divergent species that are also ecologically distinct, based on adult life history. These patterns are incongruous with the phenotypic variation that informed prior taxonomy, and most subspecies were not supported as distinct evolutionary lineages. One of the nominal subspecies was found to be a cryptic species; consequently, we elevate C. p. laetipennis (Horn, 1913) to a full species. Although nuclear and mtDNA datasets recovered broadly similar evolutionary units, mito-nuclear discordance was more common than expected, being observed between nearly all geographically overlapping taxonomic pairs. Additionally, a pattern of ‘mitochondrial displacement’ was observed, where mitochondria from one species unidirectionally displace others. Overall, we found that geographically associated life history factors better predict genomic divergence than phenotype and mitochondrial genealogies, and consequently taxon identifications based on mtDNA (e.g., DNA barcodes) may be misleading

Interannual and spatial impacts of phenological transitions, growing season length, and spring and autumn temperatures on carbon sequestration: A North America flux data synthesis

Understanding feedbacks of ecosystem carbon sequestration to climate change is an urgent step in developing future ecosystem models. Using 187 site-years of flux data observed at 24 sites covering three plant functional types (i.e. evergreen forests (EF), deciduous forests (DF) and non-forest ecosystems (NF) (e.g., crop, grassland, wetland)) in North America, we present an analysis of both interannual and spatial relationships between annual net ecosystem production (NEP) and phenological indicators, including the flux-based carbon uptake period (CUP) and its transitions, degree-day-derived growing season length (GSL), and spring and autumn temperatures. Diverse responses were acquired between annul NEP and these indicators across PFTs. Forest ecosystems showed consistent patterns and sensitivities in the responses of annual NEP to CUP and its transitions both interannually and spatially. The NF ecosystems, on the contrary, exhibited different trends between interannual and spatial relationships. The impact of CUP onset on annual NEP in NF ecosystems was interannually negative but spatially positive. Generally, the GSL was observed to be a likely good indicator of annual NEP for all PFTs both interannually and spatially, although with relatively moderate correlations in NF sites. Both spring and autumn temperatures were positively correlated with annual NEP across sites while this potential was greatly reduced temporally with only negative impacts of autumn temperature on annual NEP in DF sites. Our analysis showed that DF ecosystems have the highest efficiency in accumulating NEP from warmer spring temperature and prolonged GSL, suggesting that future climate warming will favor deciduous species over evergreen species, and supporting the earlier observation that ecosystems with the greatest net carbon uptake have the longest GSL

Interannual and spatial impacts of phenological transitions, growing season length, and spring and autumn temperatures on carbon sequestration: A North America flux data synthesis

Understanding feedbacks of ecosystem carbon sequestration to climate change is an urgent step in developing future ecosystem models. Using 187 site-years of flux data observed at 24 sites covering three plant functional types (i.e. evergreen forests (EF), deciduous forests (DF) and non-forest ecosystems (NF) (e.g., crop, grassland, wetland)) in North America, we present an analysis of both interannual and spatial relationships between annual net ecosystem production (NEP) and phenological indicators, including the flux-based carbon uptake period (CUP) and its transitions, degree-day-derived growing season length (GSL), and spring and autumn temperatures. Diverse responses were acquired between annul NEP and these indicators across PFTs. Forest ecosystems showed consistent patterns and sensitivities in the responses of annual NEP to CUP and its transitions both interannually and spatially. The NF ecosystems, on the contrary, exhibited different trends between interannual and spatial relationships. The impact of CUP onset on annual NEP in NF ecosystems was interannually negative but spatially positive. Generally, the GSL was observed to be a likely good indicator of annual NEP for all PFTs both interannually and spatially, although with relatively moderate correlations in NF sites. Both spring and autumn temperatures were positively correlated with annual NEP across sites while this potential was greatly reduced temporally with only negative impacts of autumn temperature on annual NEP in DF sites. Our analysis showed that DF ecosystems have the highest efficiency in accumulating NEP from warmer spring temperature and prolonged GSL, suggesting that future climate warming will favor deciduous species over evergreen species, and supporting the earlier observation that ecosystems with the greatest net carbon uptake have the longest GSL

Elevated A20 promotes TNF-induced and RIPK1-dependent intestinal epithelial cell death

Intestinal epithelial cell (IEC) death is a common feature of inflammatory bowel disease (IBD) that triggers inflammation by compromising barrier integrity. In many patients with IBD, epithelial damage and inflammation are TNF-dependent. Elevated TNF production in IBD is accompanied by increased expression of the TNFAIP3 gene, which encodes A20, a negative feedback regulator of NF-κB. A20 in intestinal epithelium from patients with IBD coincided with the presence of cleaved caspase-3, and A20 transgenic (Tg) mice, in which A20 is expressed from an IEC-specific promoter, were highly susceptible to TNF-induced IEC death, intestinal damage, and shock. A20-expressing intestinal organoids were also susceptible to TNF-induced death, demonstrating that enhanced TNF-induced apoptosis was a cell-autonomous property of A20. This effect was dependent on Receptor Interacting Protein Kinase 1 (RIPK1) activity, and A20 was found to associate with the Ripoptosome complex, potentiating its ability to activate caspase-8. A20-potentiated RIPK1-dependent apoptosis did not require the A20 deubiquitinase (DUB) domain and zinc finger 4 (ZnF4), which mediate NF-κB inhibition in fibroblasts, but was strictly dependent on ZnF7 and A20 dimerization. We suggest that A20 dimers bind linear ubiquitin to stabilize the Ripoptosome and potentiate its apoptosis-inducing activity