Expanding the search for galaxies at z ~7-10 with new NICMOS Parallel Fields

We have carried out a search for galaxies at z ~ 7-10 in ~14.4 sq. arcmin of new NICMOS parallel imaging taken in the Great Observatories Origins Deep Survey (GOODS, 5.9 sq. arcmin), the Cosmic Origins Survey (COSMOS, 7.2 sq. arcmin), and SSA22 (1.3 sq. arcmin). These images reach 5 sigma sensitivities of J110 = 26.0-27.5 (AB), and combined they increase the amount of deep near-infrared data by more than 60% in fields where the investment in deep optical data has already been made. We find no z>7 candidates in our survey area, consistent with the Bouwens et al. (2008) measurements at z~7 and 9 (over 23 sq. arcmin), which predict 0.7 galaxies at z~7 and <0.03 galaxies at z~9. We estimate that 10-20% of z>7 galaxies are missed by this survey, due to incompleteness from foreground contamination by faint sources. For the case of luminosity evolution, assuming a Schecter parameterization with a typical phi* = 10^-3 Mpc^-3, we find M* > -20.0 for z~7 and M* > -20.7 for z~9 (68% confidence). This suggests that the downward luminosity evolution of LBGs continues to z~7, although our result is marginally consistent with the z~6 LF of Bouwens et al.(2006, 2007). In addition we present newly-acquired deep MMT/Megacam imaging of the z~9 candidate JD2325+1433, first presented in Henry et al. (2008). The resulting weak but significant detection at i' indicates that this galaxy is most likely an interloper at z~2.7.Comment: Accepted to ApJ. Replacement includes updated discussion of incompleteness from foreground contaminatio

Recommendations of the task force on public policy

This is the published version, reproduced here with permission from the publisher. This article is also available electronically from http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2741851/.The Task Force on Public Policy was established by the Association for Behavior Analysis to examine ways to encourage members to contribute to policymaking relevant to the public interest. Members discussed issues pertinent to this activity and summarized their discussion in a formal report.' Recommendations of the Task Force for conducting and disseminating policy research and for training, technical assistance, and other services supportive of behavior-analytic research in the public policy arena are presented here

Evidence that breast cancer risk at the 2q35 locus is mediated through IGFBP5 regulation.

GWAS have identified a breast cancer susceptibility locus on 2q35. Here we report the fine mapping of this locus using data from 101,943 subjects from 50 case-control studies. We genotype 276 SNPs using the 'iCOGS' genotyping array and impute genotypes for a further 1,284 using 1000 Genomes Project data. All but two, strongly correlated SNPs (rs4442975 G/T and rs6721996 G/A) are excluded as candidate causal variants at odds against &gt;100:1. The best functional candidate, rs4442975, is associated with oestrogen receptor positive (ER+) disease with an odds ratio (OR) in Europeans of 0.85 (95% confidence interval=0.84-0.87; P=1.7 × 10(-43)) per t-allele. This SNP flanks a transcriptional enhancer that physically interacts with the promoter of IGFBP5 (encoding insulin-like growth factor-binding protein 5) and displays allele-specific gene expression, FOXA1 binding and chromatin looping. Evidence suggests that the g-allele confers increased breast cancer susceptibility through relative downregulation of IGFBP5, a gene with known roles in breast cell biology

Peripheral Delivery of a CNS Targeted, Metalo-Protease Reduces Aβ Toxicity in a Mouse Model of Alzheimer's Disease

Alzheimer's disease (AD), an incurable, progressive neurodegenerative disorder, is the most common form of dementia. Therapeutic options have been elusive due to the inability to deliver proteins across the blood-brain barrier (BBB). In order to improve the therapeutic potential for AD, we utilized a promising new approach for delivery of proteins across the BBB. We generated a lentivirus vector expressing the amyloid β-degrading enzyme, neprilysin, fused to the ApoB transport domain and delivered this by intra-peritoneal injection to amyloid protein precursor (APP) transgenic model of AD. Treated mice had reduced levels of Aβ, reduced plaques and increased synaptic density in the CNS. Furthermore, mice treated with the neprilysin targeting the CNS had a reversal of memory deficits. Thus, the addition of the ApoB transport domain to the secreted neprilysin generated a non-invasive therapeutic approach that may be a potential treatment in patients with AD

Immuno-transcriptomic profiling of extracranial pediatric solid malignancies.

We perform an immunogenomics analysis utilizing whole-transcriptome sequencing of 657 pediatric extracranial solid cancer samples representing 14 diagnoses, and additionally utilize transcriptomes of 131 pediatric cancer cell lines and 147 normal tissue samples for comparison. We describe patterns of infiltrating immune cells, T cell receptor (TCR) clonal expansion, and translationally relevant immune checkpoints. We find that tumor-infiltrating lymphocytes and TCR counts vary widely across cancer types and within each diagnosis, and notably are significantly predictive of survival in osteosarcoma patients. We identify potential cancer-specific immunotherapeutic targets for adoptive cell therapies including cell-surface proteins, tumor germline antigens, and lineage-specific transcription factors. Using an orthogonal immunopeptidomics approach, we find several potential immunotherapeutic targets in osteosarcoma and Ewing sarcoma and validated PRAME as a bona fide multi-pediatric cancer target. Importantly, this work provides a critical framework for immune targeting of extracranial solid tumors using parallel immuno-transcriptomic and -peptidomic approaches

Facile formation of highly mobile supported lipid bilayers on surface-quaternized pH-responsive polymer brushes

Poly(2-dimethylamino)ethyl methacrylate) (PDMA) brushes are grown from planar substrates via surface atom transfer radical polymerization (ATRP). Quaternization of these brushes is conducted using 1-iodooctadecane in n-hexane, which is a non-solvent for PDMA. Ellipsometry, AFM, and water contact angle measurements show that surface-confined quaternization occurs under these conditions, producing pH-responsive brushes that have a hydrophobic upper surface. Systematic variation of the 1-iodooctadecane concentration and reaction time enables the mean degree of surface quaternization to be optimized. Relatively low degrees of surface quaternization (ca. 10 mol % as judged by XPS) produce brushes that enable the formation of supported lipid bilayers, with the hydrophobic pendent octadecyl groups promoting in situ rupture of lipid vesicles. Control experiments confirm that quaternized PDMA brushes prepared in a good brush solvent (THF) produce non-pH-responsive brushes, presumably because the pendent octadecyl groups form micelle-like physical cross-links throughout the brush layer. Supported lipid bilayers (SLBs) can also be formed on the non-quaternized PDMA precursor brushes, but such structures proved to be unstable to small changes in pH. Thus, surface quaternization of PDMA brushes using 1-iodooctadecane in n-hexane provides the best protocol for the formation of robust SLBs. Fluorescence recovery after photobleaching (FRAP) studies of such SLBs indicate diffusion coefficients (2.8 ± 0.3 μm s–1) and mobile fractions (98 ± 2%) that are comparable to the literature data reported for SLBs prepared directly on planar glass substrates

The biophysical climate mitigation potential of boreal peatlands during the growing season

Peatlands and forests cover large areas of the boreal biome and are critical for global climate regulation. They also regulate regional climate through heat and water vapour exchange with the atmosphere. Understanding how land-atmosphere interactions in peatlands differ from forests may therefore be crucial for modelling boreal climate system dynamics and for assessing climate benefits of peatland conservation and restoration. To assess the biophysical impacts of peatlands and forests on peak growing season air temperature and humidity, we analysed surface energy fluxes and albedo from 35 peatlands and 37 evergreen needleleaf forests-the dominant boreal forest type-and simulated air temperature and vapour pressure deficit (VPD) over hypothetical homogeneous peatland and forest landscapes. We ran an evapotranspiration model using land surface parameters derived from energy flux observations and coupled an analytical solution for the surface energy balance to an atmospheric boundary layer (ABL) model. We found that peatlands, compared to forests, are characterized by higher growing season albedo, lower aerodynamic conductance, and higher surface conductance for an equivalent VPD. This combination of peatland surface properties results in a similar to 20% decrease in afternoon ABL height, a cooling (from 1.7 to 2.5 degrees C) in afternoon air temperatures, and a decrease in afternoon VPD (from 0.4 to 0.7 kPa) for peatland landscapes compared to forest landscapes. These biophysical climate impacts of peatlands are most pronounced at lower latitudes (similar to 45 degrees N) and decrease toward the northern limit of the boreal biome (similar to 70 degrees N). Thus, boreal peatlands have the potential to mitigate the effect of regional climate warming during the growing season. The biophysical climate mitigation potential of peatlands needs to be accounted for when projecting the future climate of the boreal biome, when assessing the climate benefits of conserving pristine boreal peatlands, and when restoring peatlands that have experienced peatland drainage and mining.Peer reviewe

Identification of a Functional Genetic Variant at 16q12.1 for Breast Cancer Risk: Results from the Asia Breast Cancer Consortium

Genetic factors play an important role in the etiology of breast cancer. We carried out a multi-stage genome-wide association (GWA) study in over 28,000 cases and controls recruited from 12 studies conducted in Asian and European American women to identify genetic susceptibility loci for breast cancer. After analyzing 684,457 SNPs in 2,073 cases and 2,084 controls in Chinese women, we evaluated 53 SNPs for fast-track replication in an independent set of 4,425 cases and 1,915 controls of Chinese origin. Four replicated SNPs were further investigated in an independent set of 6,173 cases and 6,340 controls from seven other studies conducted in Asian women. SNP rs4784227 was consistently associated with breast cancer risk across all studies with adjusted odds ratios (95% confidence intervals) of 1.25 (1.20−1.31) per allele (P = 3.2×10−25) in the pooled analysis of samples from all Asian samples. This SNP was also associated with breast cancer risk among European Americans (per allele OR  = 1.19, 95% CI  = 1.09−1.31, P = 1.3×10−4, 2,797 cases and 2,662 controls). SNP rs4784227 is located at 16q12.1, a region identified previously for breast cancer risk among Europeans. The association of this SNP with breast cancer risk remained highly statistically significant in Asians after adjusting for previously-reported SNPs in this region. In vitro experiments using both luciferase reporter and electrophoretic mobility shift assays demonstrated functional significance of this SNP. These results provide strong evidence implicating rs4784227 as a functional causal variant for breast cancer in the locus 16q12.1 and demonstrate the utility of conducting genetic association studies in populations with different genetic architectures

Global Patterns and Controls of Nutrient Immobilization On Decomposing Cellulose In Riverine Ecosystems

Microbes play a critical role in plant litter decomposition and influence the fate of carbon in rivers and riparian zones. When decomposing low-nutrient plant litter, microbes acquire nitrogen (N) and phosphorus (P) from the environment (i.e., nutrient immobilization), and this process is potentially sensitive to nutrient loading and changing climate. Nonetheless, environmental controls on immobilization are poorly understood because rates are also influenced by plant litter chemistry, which is coupled to the same environmental factors. Here we used a standardized, low-nutrient organic matter substrate (cotton strips) to quantify nutrient immobilization at 100 paired stream and riparian sites representing 11 biomes worldwide. Immobilization rates varied by three orders of magnitude, were greater in rivers than riparian zones, and were strongly correlated to decomposition rates. In rivers, P immobilization rates were controlled by surface water phosphate concentrations, but N immobilization rates were not related to inorganic N. The N:P of immobilized nutrients was tightly constrained to a molar ratio of 10:1 despite wide variation in surface water N:P. Immobilization rates were temperature-dependent in riparian zones but not related to temperature in rivers. However, in rivers nutrient supply ultimately controlled whether microbes could achieve the maximum expected decomposition rate at a given temperature