Oregon 2100: projected climatic and ecological changes

Greenhouse climatic warming is underway and exacerbated by human activities. Future outcomes of these processes can be projected using computer models checked against climatic changes during comparable past atmospheric compositions. This study gives concise quantitative predictions for future climate, landscapes, soils, vegetation, and marine and terrestrial animals of Oregon. Fossil fuel burning and other human activities by the year 2100 are projected to yield atmospheric CO2 levels of about 600-850 ppm (SRES A1B and B1), well above current levels of 400 ppm and preindustrial levels of 280 ppm. Such a greenhouse climate was last recorded in Oregon during the middle Miocene, some 16 million years ago. Oregon’s future may be guided by fossil records of the middle Miocene, as well as ongoing studies on the environmental tolerances of Oregon plants and animals, and experiments on the biological effects of global warming. As carbon dioxide levels increase, Oregon’s climate will move toward warm temperate, humid in the west and semiarid to subhumid to the east, with increased summer and winter drought in the west. Western Oregon lowlands will become less suitable for temperate fruits and nuts and Pinot Noir grapes, but its hills will remain a productive softwood forest resource. Improved pasture and winter wheat crops will become more widespread in eastern Oregon. Tsunamis and stronger storms will exacerbate marine erosion along the Oregon Coast, with significant damage to coastal properties and cultural resources

Discovery and Characterization of 2-Aminobenzimidazole Derivatives as Selective NOD1 Inhibitors

SummaryNLR family proteins play important roles in innate immune response. NOD1 (NLRC1) activates various signaling pathways including NF-κB in response to bacterial ligands. Hereditary polymorphisms in the NOD1 gene are associated with asthma, inflammatory bowel disease, and other disorders. Using a high throughput screening (HTS) assay measuring NOD1-induced NF-κB reporter gene activity, followed by multiple downstream counter screens that eliminated compounds impacting other NF-κB effectors, 2-aminobenzimidazole compounds were identified that selectively inhibit NOD1. Mechanistic studies of a prototypical compound, Nodinitib-1 (ML130; CID-1088438), suggest that these small molecules cause conformational changes of NOD1 in vitro and alter NOD1 subcellular targeting in cells. Altogether, this inaugural class of inhibitors provides chemical probes for interrogating mechanisms regulating NOD1 activity and tools for exploring the roles of NOD1 in various infectious and inflammatory diseases

The Regeneration Games: Commodities, Gifts and the Economics of London 2012

This paper considers contradictions between two concurrent and tacit conceptions of the Olympic ‘legacy’, setting out one conception that understands the games and their legacies as gifts alongside and as counterpoint to the prevailing discourse, which conceives Olympic assets as commodities. The paper critically examines press and governmental discussion of legacy, in order to locate these in the context of a wider perspective contrasting ‘gift’ and ‘commodity’ Olympics – setting anthropological conceptions of gift-based sociality as a necessary supplement to contractual and dis-embedded socioeconomic organizational assumptions underpinning the commodity Olympics. Costbenefit planning is central to modern city building and mega-event delivery. The paper considers the insufficiency of this approach as the exclusive paradigm within which to frame and manage a dynamic socio-economic and cultural legacy arising from the 2012 games

FastJet user manual

FastJet is a C++ package that provides a broad range of jet finding and analysis tools. It includes efficient native implementations of all widely used 2-to-1 sequential recombination jet algorithms for pp and e+e- collisions, as well as access to 3rd party jet algorithms through a plugin mechanism, including all currently used cone algorithms. FastJet also provides means to facilitate the manipulation of jet substructure, including some common boosted heavy-object taggers, as well as tools for estimation of pileup and underlying-event noise levels, determination of jet areas and subtraction or suppression of noise in jets.Comment: 69 pages. FastJet 3 is available from http://fastjet.fr

The anti-k_t jet clustering algorithm

The k_t and Cambridge/Aachen inclusive jet finding algorithms for hadron-hadron collisions can be seen as belonging to a broader class of sequential recombination jet algorithms, parametrised by the power of the energy scale in the distance measure. We examine some properties of a new member of this class, for which the power is negative. This ``anti-k_t'' algorithm essentially behaves like an idealised cone algorithm, in that jets with only soft fragmentation are conical, active and passive areas are equal, the area anomalous dimensions are zero, the non-global logarithms are those of a rigid boundary and the Milan factor is universal. None of these properties hold for existing sequential recombination algorithms, nor for cone algorithms with split--merge steps, such as SISCone. They are however the identifying characteristics of the collinear unsafe plain ``iterative cone'' algorithm, for which the anti-k_t algorithm provides a natural, fast, infrared and collinear safe replacement.Comment: 12 pages, 5 figures. Small changes made for publication. Version published in JHE

Standardized Direct Observation Assessment Tool: Using a Training Video.

BACKGROUND: We developed a DVD training tool to educate physicians evaluating emergency residents on accurate Standardized Direct Observation Assessment Tool (SDOT) application. OBJECTIVE: Our goal was to assess whether this training video improved attendings\u27 and senior residents\u27 SDOT use. METHODS: Participants voluntarily completed SDOT evaluations based on a scripted test video. A DVD with positive and negative scenarios of proper SDOT use was viewed. It included education on appropriate recording of 26 behaviors. The test scenario was viewed again and follow-up SDOTs submitted. Performances by attendings and residents on the pre- and post-test SDOTs were compared. RESULTS: Twenty-six attendings and 26 senior residents participated. Prior SDOT experience was noted for 8 attendings and 11 residents. For 20 anchors, participants recorded observed behaviors with statistically significant difference on one each of the pretest (no. 20; p = 0.034) and post-test (no. 14; p = 0.041) SDOTs. On global competency assessments, pretest medical knowledge (p = 0.016) differed significantly between groups. The training intervention changed one anchor (no. 5; p = 0.035) and one global assessment (systems-based practice; p = 0.031) more negatively for residents. Recording SDOTs with exact agreement occurred 48.73% for attendings pretest and 54.41% post-test; resident scores were 45.86% and 49.55%, respectively. DVD exposure slightly raised attending scores (p = 0.289) and significantly lowered resident scores (p = 0.046). CONCLUSIONS: Exposure to an independently developed SDOT training video tended to raise attending scores, though without significance, while at the same time lowered senior resident scores statistically significantly. Emergency attendings\u27 and senior residents\u27 SDOT scoring rarely differed with significance; about half of anchor behaviors were recorded with exact agreement. This suggests senior residents, with appropriate education, may participate in SDOT assessment

Genetic Background Can Result in a Marked or Minimal Effect of Gene Knockout (GPR55 and CB2 Receptor) in Experimental Autoimmune Encephalomyelitis Models of Multiple Sclerosis

PMCID: PMC379391

Single-cell profiling of human dura and meningioma reveals cellular meningeal landscape and insights into meningioma immune response

BACKGROUND: Recent investigations of the meninges have highlighted the importance of the dura layer in central nervous system immune surveillance beyond a purely structural role. However, our understanding of the meninges largely stems from the use of pre-clinical models rather than human samples. METHODS: Single-cell RNA sequencing of seven non-tumor-associated human dura samples and six primary meningioma tumor samples (4 matched and 2 non-matched) was performed. Cell type identities, gene expression profiles, and T cell receptor expression were analyzed. Copy number variant (CNV) analysis was performed to identify putative tumor cells and analyze intratumoral CNV heterogeneity. Immunohistochemistry and imaging mass cytometry was performed on selected samples to validate protein expression and reveal spatial localization of select protein markers. RESULTS: In this study, we use single-cell RNA sequencing to perform the first characterization of both non-tumor-associated human dura and primary meningioma samples. First, we reveal a complex immune microenvironment in human dura that is transcriptionally distinct from that of meningioma. In addition, we characterize a functionally diverse and heterogenous landscape of non-immune cells including endothelial cells and fibroblasts. Through imaging mass cytometry, we highlight the spatial relationship among immune cell types and vasculature in non-tumor-associated dura. Utilizing T cell receptor sequencing, we show significant TCR overlap between matched dura and meningioma samples. Finally, we report copy number variant heterogeneity within our meningioma samples. CONCLUSIONS: Our comprehensive investigation of both the immune and non-immune cellular landscapes of human dura and meningioma at single-cell resolution builds upon previously published data in murine models and provides new insight into previously uncharacterized roles of human dura

Characterization of the genomic and immunologic diversity of malignant brain tumors through multisector analysis

Despite some success in secondary brain metastases, targeted or immune-based therapies have shown limited efficacy against primary brain malignancies such as glioblastoma (GBM). Although the intratumoral heterogeneity of GBM is implicated in treatment resistance, it remains unclear whether this diversity is observed within brain metastases and to what extent cancer cell-intrinsic heterogeneity sculpts the local immune microenvironment. Here, we profiled the immunogenomic state of 93 spatially distinct regions from 30 malignant brain tumors through whole-exome, RNA, and T-cell receptor sequencing. Our analyses identified differences between primary and secondary malignancies, with gliomas displaying more spatial heterogeneity at the genomic and neoantigen levels. In addition, this spatial diversity was recapitulated in the distribution of T-cell clones in which some gliomas harbored highly expanded but spatially restricted clonotypes. This study defines the immunogenomic landscape across a cohort of malignant brain tumors and contains implications for the design of targeted and immune-based therapies against intracranial malignancies. SIGNIFICANCE: This study describes the impact of spatial heterogeneity on genomic and immunologic characteristics of gliomas and brain metastases. The results suggest that gliomas harbor significantly greater intratumoral heterogeneity of genomic alterations, neoantigens, and T-cell clones than brain metastases, indicating the importance of multisector analysis for clinical or translational studies