4,701 research outputs found
Frequent side chain methyl carbon‐oxygen hydrogen bonding in proteins revealed by computational and stereochemical analysis of neutron structures
The propensity of backbone Cα atoms to engage in carbon‐oxygen (CH···O) hydrogen bonding is well‐appreciated in protein structure, but side chain CH···O hydrogen bonding remains largely uncharacterized. The extent to which side chain methyl groups in proteins participate in CH···O hydrogen bonding is examined through a survey of neutron crystal structures, quantum chemistry calculations, and molecular dynamics simulations. Using these approaches, methyl groups were observed to form stabilizing CH···O hydrogen bonds within protein structure that are maintained through protein dynamics and participate in correlated motion. Collectively, these findings illustrate that side chain methyl CH···O hydrogen bonding contributes to the energetics of protein structure and folding. Proteins 2015; 83:403–410. © 2014 Wiley Periodicals, Inc.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/110709/1/prot24724-sup-0001-suppinfo01.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/110709/2/prot24724.pd
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
A novel promoter controls Cyp19a1 gene expression in mouse adipose tissue
<p>Abstract</p> <p>Background</p> <p>Aromatase, the key enzyme in estrogen biosynthesis, is encoded by the Cyp19a1 gene. Thus far, 3 unique untranslated first exons associated with distinct promoters in the mouse Cyp19a1 gene have been described (brain, ovary, and testis-specific). It remains unknown whether aromatase is expressed in other mouse tissues via novel and tissue-specific promoters.</p> <p>Methods</p> <p>Real-time PCR was used to examine the aromatase expression levels in various C57BL/6 mouse tissues. 5'-rapid amplification of cDNA ends (5'-RACE) was used to determine the transcriptional start sites of Cyp19a1 transcripts. Promoter activity was measured using serial deletion mutants of DNA fused to the luciferase reporter gene. Primary mouse adipose fibroblasts were isolated and cultured from 16-week-old mouse gonadal fat pads.</p> <p>Results</p> <p>We systematically analyzed Cyp19a1 expression in a large number of mouse tissues, and demonstrated for the first time that aromatase was expressed in the male but not female gonadal fat pad. Subcutaneous and brown adipose tissue did not contain detectable Cyp19a1 mRNA. We used 5'-RACE to clone a novel gonadal fat-specific untranslated first exon, which is spliced onto a common junction 15 bp upstream of the translation start site. This adipose-specific first exon was mapped to approximately 75 kb upstream of the translation start site. Transfection of luciferase reporter gene plasmids containing the promoter region upstream of the adipose-specific first exon into murine 3T3-L1 adipose fibroblasts demonstrated significant basal promoter activity conferred primarily by the sequence located at -343/-1 bp. Dexamethasone significantly induced activity of this adipose-specific promoter region. Adipose-specific Cyp19a1 mRNA was expressed in primary mouse adipose fibroblasts and significantly induced by dexamethasone alone or serum plus dexamethasone.</p> <p>Conclusion</p> <p>Taken together, this research identified a novel, adipose-specific first exon of Cyp19a1 and its hormonally regulated promoter region in male murine gonadal fat. These results expand the known 5'-regulatory region of the murine Cyp19a1 gene to 75 kb upstream of the translation start site. Cyp19a1 expression in mouse adipose tissue may play an important role in reproductive biology and lipid metabolism.</p
Data Collection at Fifteen Selected Creeks in Support of Shallow Water Dredging on Virginia’s Middle Peninsula - Methods & Data Report
Federal funding has been historically available for the Army Corps of Engineers for shallow draft navigation projects. However, past and recent subsidies have not provided ample funding at levels to sustain maintenance dredging for the 17 federal navigation channels on the Middle Peninsula. Further, funding for maintenance of non-federal channels has been historically neglected by the Commonwealth of Virginia until the Virginia General Assembly established the Virginia Waterway Maintenance Fund in 2018. For the past decade the Middle Peninsula Chesapeake Bay Public Access Authority, the Middle Peninsula Planning District Commission and its member jurisdictions, and the Virginia Institute of Marine Science Shoreline Studies Program have worked to advance local solutions and alternatives to address dredging needs in the Commonwealth
Coastal dune dynamics in embayed settings with sea-level rise – Examples from the exposed and macrotidal north coast of SW England
Coastal dune systems are natural forms of coastal defence, but are expected to exhibit increased erosion rates due to climate change impacts, notably sea-level rise and, potentially, increased storminess. This is especially the case in embayed coastal settings, i.e., where there are no significant sediment inputs into the beach/dune system from longshore sources. Dune development is closely linked to that of beaches that lie seaward, but their temporal dynamics tend to be asynchronous. So, whereas beaches are generally highly variable over a short- to medium-term (event–decadal) time scales, potentially obscuring a longer-term (decadal–centennial) sea-level signal, dunes display a low-pass filtered response which may contain a sea-level signal.
In this study, we investigate the decadal-scale, inter-annual dynamics of 25 embayed coastal dune systems along the exposed and macrotidal north coast of SW England. We then compare the observed behaviour with that hindcasted from simple parametric models and forecast future dune retreat rates due to sea-level rise. We show that practically all exposed dune systems show retreat with a regionally-averaged retreat rate of the dune foot of 0.5 m yr−1. The majority of retreat occurred over a small number of especially energetic winters and it was found that dune retreat is not automatically linked to dune volumetric change. Many of the retreating dune systems display so called ‘dune roll-over’, characterised by removal of sediment from the dune face and deposition at the dune top. Observed dune retreat rates were 2–3 times larger than predicted using simple parametric retreat models forced by sea-level rise. This suggests that the retreat models are inappropriate and/or that sea-level rise in itself may be insufficient to explain the observed retreat and that increased winter storminess may be implicated.
A key factor in driving dune retreat is considered to be the number of hours that waves reach the dune foot or the excess runup energy present at the dune foot elevation. Both sea-level rise and enhanced storminess will increase exposure of the dune foot to energetic wave action and this is expected to accelerate dune retreat rates in these settings. Application of parametric shoreline retreat models that account for the acceleration in rate of sea-level rise predicts c. 40 m of dune retreat by 2100 with a considerable range in retreat (20–75 m), resulting from uncertainty in model choice and parameterisation. Simply extrapolating the current dune retreat rate also results in c. 40 m of dune retreat by 2100, but this approach ignores the potential acceleration in dune retreat rate due to an increase in the rate of sea-level rise.
The combination of analysis of multi-annual coastal dune morphological change along with application of dune retreat models can provide useful insights into future dune evolution for coastal planners and managers
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Gladstone and Scott: Family, identity, and nation
In the 175 years since his death, Walter Scott has regularly been hailed as an influence by politicians. Amongst the poet-novelist's nineteenth-century political admirers, William Ewart Gladstone was possibly the most ardent, genuine, and significant. Scott's poems and novels were amongst the earliest texts Gladstone read; he read no works (in English), except the Bible, so consistently or completely over such a length of time. They offered him a plethora of inspirations, ideas, and language, which he imbibed and appropriated into his public and private lives. His concept of self, his understanding of family, and his sense of home, were all forged and conducted within a Scottian frame of reference. Scott's life and works also crucially influenced Gladstone's political understanding of the Scottish nation and its people, and his conception of how he could best serve their political interests. This article casts new light on an important and influential relationship in Gladstone's life, establishing that it was neither the superficial and recreational association some have described, nor simply a ploy of an astute politician. The article falls into three parts. The first elucidates how Gladstone's consumption of Scott's writings was seminal in the formation of his private identity, both individual and familial. The second explains how Gladstone's readings of Scott fitted into the specific and serious character of his other reading and knowledge-gathering, and the third shows how the details of Gladstone's response to Scott related to the broader intellectual and cultural context of his public life. By placing Gladstone within his Scottish context, this article shows how frequently and significantly his private and public worlds intersected
Defining childhood severe falciparum malaria for intervention studies.
Background Clinical trials of interventions designed to prevent severe falciparum malaria in children require a clear endpoint. The internationally accepted definition of severe malaria is sensitive, and appropriate for clinical purposes. However, this definition includes individuals with severe nonmalarial disease and coincident parasitaemia, so may lack specificity in vaccine trials. Although there is no “gold standard” individual test for severe malaria, malaria-attributable fractions (MAFs) can be estimated among groups of children using a logistic model, which we use to test the suitability of various case definitions as trial endpoints. Methods and Findings A total of 4,583 blood samples were taken from well children in cross-sectional surveys and from 1,361 children admitted to a Kenyan District hospital with severe disease. Among children under 2 y old with severe disease and over 2,500 parasites per microliter of blood, the MAFs were above 85% in moderate- and low-transmission areas, but only 61% in a high-transmission area. HIV and malnutrition were not associated with reduced MAFs, but gastroenteritis with severe dehydration (defined by reduced skin turgor), lower respiratory tract infection (clinician's final diagnosis), meningitis (on cerebrospinal fluid [CSF] examination), and bacteraemia were associated with reduced MAFs. The overall MAF was 85% (95% confidence interval [CI] 83.8%–86.1%) without excluding these conditions, 89% (95% CI 88.4%–90.2%) after exclusions, and 95% (95% CI 94.0%–95.5%) when a threshold of 2,500 parasites/μl was also applied. Applying a threshold and exclusion criteria reduced sensitivity to 80% (95% CI 77%–83%). Conclusions The specificity of a case definition for severe malaria is improved by applying a parasite density threshold and by excluding children with meningitis, lower respiratory tract infection (clinician's diagnosis), bacteraemia, and gastroenteritis with severe dehydration, but not by excluding children with HIV or malnutrition
The Pneumonia Etiology Research for Child Health Project: A 21st Century Childhood Pneumonia Etiology Study
The Pneumonia Etiology Research for Child Health (PERCH) project is a 7-country, standardized, comprehensive evaluation of the etiologic agents causing severe pneumonia in children from developing countries. During previous etiology studies, between one-quarter and one-third of patients failed to yield an obvious etiology; PERCH will employ and evaluate previously unavailable innovative, more sensitive diagnostic techniques. Innovative and rigorous epidemiologic and analytic methods will be used to establish the causal association between presence of potential pathogens and pneumonia. By strategic selection of study sites that are broadly representative of regions with the greatest burden of childhood pneumonia, PERCH aims to provide data that reflect the epidemiologic situation in developing countries in 2015, using pneumococcal and Haemophilus influenzae type b vaccines. PERCH will also address differences in host, environmental, and/or geographic factors that might determine pneumonia etiology and, by preserving specimens, will generate a resource for future research and pathogen discovery
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