NDM-552: COMBINED PROBABILITIES OF PEAK WIND AND SNOW LOAD EVENTS

The National Building Code of Canada 2010 (NBCC) defines several loading combination scenarios for use in structural design. Appropriate combination factors are provided based on the probability of failure due to the simultaneous occurrence of the specified loads. Load Combination Cases 3 and 4 of Table 4.1.3.2.A include the combination of wind and snow loads, which are transient in nature. The recommended combination factors are intended to provide a uniform degree of reliability for design. However, in reality, the probability of the simultaneous loading due to wind and snow depends on the local meteorological climate. This probability can be more accurately simulated through the Finite Area Element (FAE) process, which studies the hour-by-hour accumulation and depletion of snow based on historical meteorological records. It takes into account variables such as wind speed and direction, temperature, humidity, water retention in a snow pack and many others. In the present work, the accumulation and depletion of snow on a modelled ground patch and the corresponding wind speeds were computed on an hourly basis to determine the correlation of wind and snow loads. Using this process, this paper investigates the interaction between wind and snow loads for 25 distinct regions in Canada, for both ground and roof snow loads

STR-940: PARAMETRIC SIMULATION OF ROOF STRUCTURAL SNOW LOADS

While the National Building Code of Canada (NBCC) provides engineers with suitable snow loading guidelines for structural design, the strict application of the code may not lead to an optimized structural design. Generalizations have been made to ensure the applicability of the code to the majority of potential structures within Canada, which result in conservative estimates in certain situations. In particular, the interaction between region-specific prevailing wind directionality, climate and roof orientation are not accounted for. However, the development of advanced physical and numerical snow simulation approaches allows for the investigation of building-specific variables that affect snow loading. The Finite Area Element (FAE) process simulates the hour-by-hour accumulation and depletion of snow on a specific building design. This tool provides detailed quantification of the probabilistic snow loading accounting for region-specific long term meteorological conditions and building-specific variables such as roof size, exposure to prevailing winds, thermal capacity and local aerodynamics. While providing a detailed assessment of the snow loads, a full FAE assessment can be both time consuming and relatively costly for many applications. This parametric analysis approach has been developed using a variety of simple building geometries to provide an approach to assess the relative impacts of many of the key variables needed to inform a design. This paper describes the physical and numerical models used for the parametric simulation of snow loads, and discusses their application to structures within Canada

The Millimeter Astronomy Legacy Team 90 GHz (MALT90) Pilot Survey

We describe a pilot survey conducted with the Mopra 22-m radio telescope in preparation for the Millimeter Astronomy Legacy Team Survey at 90 GHz (MALT90). We identified 182 candidate dense molecular clumps using six different selection criteria and mapped each source simultaneously in 16 different lines near 90 GHz. We present a summary of the data and describe how the results of the pilot survey shaped the design of the larger MALT90 survey. We motivate our selection of target sources for the main survey based on the pilot detection rates and demonstrate the value of mapping in multiple lines simultaneously at high spectral resolution.Comment: Accepted to ApJS. 23 pages and 16 figures. Full resolution version with an appendix showing all the data (12.1 MB) is available at http://malt90.bu.edu/publications/Foster_2011_Malt90Pilot.pd

CD8 T Cell Recognition of Endogenously Expressed Epstein-Barr Virus Nuclear Antigen 1

The Epstein-Barr virus (EBV) nuclear antigen (EBNA)1 contains a glycine-alanine repeat (GAr) domain that appears to protect the antigen from proteasomal breakdown and, as measured in cytotoxicity assays, from major histocompatibility complex (MHC) class I–restricted presentation to CD8+ T cells. This led to the concept of EBNA1 as an immunologically silent protein that although unique in being expressed in all EBV malignancies, could not be exploited as a CD8 target. Here, using CD8+ T cell clones to native EBNA1 epitopes upstream and downstream of the GAr domain and assaying recognition by interferon γ release, we show that the EBNA1 naturally expressed in EBV-transformed lymphoblastoid cell lines (LCLs) is in fact presented to CD8+ T cells via a proteasome/peptide transporter–dependent pathway. Furthermore, LCL recognition by such CD8+ T cells, although slightly lower than seen with paired lines expressing a GAr-deleted EBNA1 protein, leads to strong and specific inhibition of LCL outgrowth in vitro. Endogenously expressed EBNA1 is therefore accessible to the MHC class I pathway despite GAr-mediated stabilization of the mature protein. We infer that EBNA1-specific CD8+ T cells do play a role in control of EBV infection in vivo and might be exploitable in the control of EBV+ malignancies

Cerebrospinal fluid levels of opioid peptides in fibromyalgia and chronic low back pain

BACKGROUND: The mechanism(s) of nociceptive dysfunction and potential roles of opioid neurotransmitters are unresolved in the chronic pain syndromes of fibromyalgia and chronic low back pain. METHODS: History and physical examinations, tender point examinations, and questionnaires were used to identify 14 fibromyalgia, 10 chronic low back pain and 6 normal control subjects. Lumbar punctures were performed. Met-enkephalin-Arg(6)-Phe(7 )(MEAP) and nociceptin immunoreactive materials were measured in the cerebrospinal fluid by radioimmunoassays. RESULTS: Fibromyalgia (117.6 pg/ml; 85.9 to 149.4; mean, 95% C.I.; p = 0.009) and low back pain (92.3 pg/ml; 56.9 to 127.7; p = 0.049) groups had significantly higher MEAP than the normal control group (35.7 pg/ml; 15.0 to 56.5). MEAP was inversely correlated to systemic pain thresholds. Nociceptin was not different between groups. Systemic Complaints questionnaire responses were significantly ranked as fibromyalgia > back pain > normal. SF-36 domains demonstrated severe disability for the low back pain group, intermediate results in fibromyalgia, and high function in the normal group. CONCLUSIONS: Fibromyalgia was distinguished by higher cerebrospinal fluid MEAP, systemic complaints, and manual tender points; intermediate SF-36 scores; and lower pain thresholds compared to the low back pain and normal groups. MEAP and systemic pain thresholds were inversely correlated in low back pain subjects. Central nervous system opioid dysfunction may contribute to pain in fibromyalgia

Serum neurofilament dynamics predicts neurodegeneration and clinical progression in presymptomatic Alzheimer's disease

Neurofilament light chain (NfL) is a promising fluid biomarker of disease progression for various cerebral proteopathies. Here we leverage the unique characteristics of the Dominantly Inherited Alzheimer Network and ultrasensitive immunoassay technology to demonstrate that NfL levels in the cerebrospinal fluid (n = 187) and serum (n = 405) are correlated with one another and are elevated at the presymptomatic stages of familial Alzheimer's disease. Longitudinal, within-person analysis of serum NfL dynamics (n = 196) confirmed this elevation and further revealed that the rate of change of serum NfL could discriminate mutation carriers from non-mutation carriers almost a decade earlier than cross-sectional absolute NfL levels (that is, 16.2 versus 6.8 years before the estimated symptom onset). Serum NfL rate of change peaked in participants converting from the presymptomatic to the symptomatic stage and was associated with cortical thinning assessed by magnetic resonance imaging, but less so with amyloid-β deposition or glucose metabolism (assessed by positron emission tomography). Serum NfL was predictive for both the rate of cortical thinning and cognitive changes assessed by the Mini-Mental State Examination and Logical Memory test. Thus, NfL dynamics in serum predict disease progression and brain neurodegeneration at the early presymptomatic stages of familial Alzheimer's disease, which supports its potential utility as a clinically useful biomarker

Working and learning across professional boundaries

This paper focuses on a context where interdisciplinarity intersects with interprofessionality: the work of children's services professionals who address the needs of children identified as vulnerable. It draws on evidence and perspectives from two disciplines - educational studies and health care - to consider the issues and challenges posed by learning and/or working across disciplinary boundaries and why these have proved so obdurate

Pan-Cancer Analysis of lncRNA Regulation Supports Their Targeting of Cancer Genes in Each Tumor Context

Long noncoding RNAs (lncRNAs) are commonly dys-regulated in tumors, but only a handful are known toplay pathophysiological roles in cancer. We inferredlncRNAs that dysregulate cancer pathways, onco-genes, and tumor suppressors (cancer genes) bymodeling their effects on the activity of transcriptionfactors, RNA-binding proteins, and microRNAs in5,185 TCGA tumors and 1,019 ENCODE assays.Our predictions included hundreds of candidateonco- and tumor-suppressor lncRNAs (cancerlncRNAs) whose somatic alterations account for thedysregulation of dozens of cancer genes and path-ways in each of 14 tumor contexts. To demonstrateproof of concept, we showed that perturbations tar-geting OIP5-AS1 (an inferred tumor suppressor) andTUG1 and WT1-AS (inferred onco-lncRNAs) dysre-gulated cancer genes and altered proliferation ofbreast and gynecologic cancer cells. Our analysis in-dicates that, although most lncRNAs are dysregu-lated in a tumor-specific manner, some, includingOIP5-AS1, TUG1, NEAT1, MEG3, and TSIX, synergis-tically dysregulate cancer pathways in multiple tumorcontexts

Genomic, Pathway Network, and Immunologic Features Distinguishing Squamous Carcinomas

This integrated, multiplatform PanCancer Atlas study co-mapped and identified distinguishing molecular features of squamous cell carcinomas (SCCs) from five sites associated with smokin