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The National Cryo-Electron Microscopy Facility (NCEF) at the National Cancer Institute was launched in May of 2017 to provide free and rapid access to high-resolution cryo-EM data collection to United States researchers working on problems of broad general relevance to cancer biology. The decision about suitability of projects for data collection is made on a first-come, first-served basis by NCEF staff and is based solely on the quality of the screening images provided, without need for a scientific proposal. Here we provide an overview of the operation of the facility, typical data collection procedures, and some insights that have emerged from the structures reported from data collected at the facility.
Normal odd-chain SFA (OCSFA), particularly tridecanoic acid (n-13 : 0), pentadecanoic acid (n-15 : 0) and heptadecanoic acid (n-17 : 0), are normal components of dairy products, beef and seafood. The ratio of n-15 : 0:n-17 : 0 in ruminant foods (dairy products and beef) is 2:1, while in seafood and human tissues it is 1:2, and their appearance in plasma is often used as a marker for ruminant fat intake. Human elongases encoded by elongation of very long-chain fatty acid (ELOVL)1, ELOVL3, ELOVL6 and ELOVL7 catalyse biosynthesis of the dominant even-chain SFA; however, there are no reports of elongase function on OCSFA. ELOVL transfected MCF7 cells were treated with n-13 : 0, n-15 : 0 or n-17 : 0 (80 µm) and products analysed. ELOVL6 catalysed elongation of n-13 : 0→n-15 : 0 and n-15 : 0→n-17 : 0; and ELOVL7 had modest activity toward n-15 : 0 (n-15 : 0→n-17 : 0). No elongation activity was detected for n-17 : 0→n-19 : 0. Our data expand ELOVL specificity to OCSFA, providing the first molecular evidence demonstrating ELOVL6 as the major elongase acting on OCSFA n-13 : 0 and n-15 : 0 fatty acids. Studies of food intake relying on OCSFA as a biomarker should consider endogenous human metabolism when relying on OCSFA ratios to indicate specific food intake.
The role that vitamin D plays in pulmonary function remains uncertain. Epidemiological studies reported mixed findings for serum 25-hydroxyvitamin D (25(OH)D)–pulmonary function association. We conducted the largest cross-sectional meta-analysis of the 25(OH)D–pulmonary function association to date, based on nine European ancestry (EA) cohorts (n 22 838) and five African ancestry (AA) cohorts (n 4290) in the Cohorts for Heart and Aging Research in Genomic Epidemiology Consortium. Data were analysed using linear models by cohort and ancestry. Effect modification by smoking status (current/former/never) was tested. Results were combined using fixed-effects meta-analysis. Mean serum 25(OH)D was 68 (sd 29) nmol/l for EA and 49 (sd 21) nmol/l for AA. For each 1 nmol/l higher 25(OH)D, forced expiratory volume in the 1st second (FEV1) was higher by 1·1 ml in EA (95 % CI 0·9, 1·3; P<0·0001) and 1·8 ml (95 % CI 1·1, 2·5; P<0·0001) in AA (Prace difference=0·06), and forced vital capacity (FVC) was higher by 1·3 ml in EA (95 % CI 1·0, 1·6; P<0·0001) and 1·5 ml (95 % CI 0·8, 2·3; P=0·0001) in AA (Prace difference=0·56). Among EA, the 25(OH)D–FVC association was stronger in smokers: per 1 nmol/l higher 25(OH)D, FVC was higher by 1·7 ml (95 % CI 1·1, 2·3) for current smokers and 1·7 ml (95 % CI 1·2, 2·1) for former smokers, compared with 0·8 ml (95 % CI 0·4, 1·2) for never smokers. In summary, the 25(OH)D associations with FEV1 and FVC were positive in both ancestries. In EA, a stronger association was observed for smokers compared with never smokers, which supports the importance of vitamin D in vulnerable populations.
DNA nanostructures are a set of materials with well-defined physical, chemical, and biological properties that can be used on their own or incorporated with other materials for many applications. Herein, the practical aspects of utilizing DNA nanostructures (structural or dynamic) as materials are comprehensively covered. This article first summarizes properties of DNA molecules and practical considerations and then discusses the fundamental design principles of structural DNA nanostructures. Finally, various aspects of dynamic DNA nanostructure-based actuation and computation are included.
Infants and young children are frequently colonized with C. difficile but rarely have symptomatic disease. However, C. difficile testing remains prevalent in this age group.
To design a computerized provider order entry (CPOE) alert to decrease testing for C. difficile in young children and infants.
An interventional age-targeted before-after trial with comparison group
Monroe Carell Jr. Children’s Hospital at Vanderbilt University, Nashville, Tennessee.
All children seen in the inpatient or emergency room settings from July 2012 through July 2013 (pre-CPOE alert) and September 2013 through September 2014 (post-CPOE alert)
In August of 2013, we implemented a CPOE alert advising against testing in infants and young children based on the American Academy of Pediatrics recommendations with an optional override. We further offered healthcare providers educational seminars regarding recommended C. difficile testing.
The average monthly testing rate significantly decreased after the CPOE alert for children 0–11 months old (11.5 pre-alert vs 0 post-alert per 10,000 patient days; P<.001) and 12–35 months old (61.6 pre-alert vs 30.1 post-alert per 10,000 patients days; P<.001), but not for those children ≥36 months old (50.9 pre-alert vs 46.4 post-alert per 10,000 patient days; P=.3) who were not targeted with a CPOE alert. There were no complications in those children who testing positive for C. difficile.
The average monthly testing rate for C. difficile for children <35 months old decreased without complication after the use of a CPOE alert in those who tested positive for C. difficile.
Transition metal dichalcogenides such as WS2 show exciting promise in electronic and optoelectronic applications. Significant variations in the transport, Raman, and photoluminescence (PL) can be found in the literature, yet it is rarely addressed why this is. In this report, Raman and PL of monolayered WS2 produced via different methods are studied and distinct features that indicate the degree of crystallinity of the material are observed. While the intensity of the LA(M) Raman mode is found to be a useful indicator to assess the crystallinity, PL is drastically more sensitive to the quality of the material than Raman spectroscopy. We also show that even exfoliated crystals, which are usually regarded as the most pristine material, can contain large amounts of defects that would not be apparent without Raman and PL measurements. These findings can be applied to the understanding of other two-dimensional heterostructured systems.
Interfacial dislocations (IDs) and half-loop arrays (HLAs) present in the
epilayers of 4H-SiC crystal are known to have a deleterious effect on device
performance. Synchrotron X-ray Topography studies carried out on n-type 4H-SiC
offcut wafers before and after epitaxial growth show that in many cases BPD
segments in the substrate are responsible for creating IDs and HLAs during CVD
growth. This paper reviews the behaviors of BPDs in the substrate during the
epitaxial growth in different cases: (1) screw-oriented BPD segments
intersecting the surface replicate directly through the interface during the
epitaxial growth and take part in stress relaxation process by creating IDs and
HLAs (Matthews-Blakeslee model  ); (2) non-screw oriented BPD half loop
intersecting the surface glides towards and replicates through the interface,
while the intersection points convert to threading edge dislocations (TEDs) and
pin the half loop, leaving straight screw segments in the epilayer and then
create IDs and HLAs; (3) edge oriented short BPD segments well below the surface
get dragged towards the interface during epitaxial growth, leaving two long
screw segments in their wake, some of which replicate through the interface and
create IDs and HLAs. The driving force for the BPDs to glide toward the
interface is thermal stress and driving force for the relaxation process to
occur is the lattice parameter difference at growth temperature which results
from the doping concentration difference between the substrate and epilayer.
While more and more long-period giant planets are discovered by direct imaging, the distribution of planets at these separations (≳5 AU) has remained largely uncertain, especially compared to planets in the inner regions of solar systems probed by RV and transit techniques. The low frequency, the detection challenges, and heterogeneous samples make determining the mass and orbit distributions of directly imaged planets at the end of a survey difficult. By utilizing Monte Carlo methods that incorporate the age, distance, and spectral type of each target, we can use all stars in the survey, not just those with detected planets, to learn about the underlying population. We have produced upper limits and direct measurements of the frequency of these planets with the most recent generation of direct imaging surveys. The Gemini NICI Planet-Finding Campaign observed 220 young, nearby stars at a median H-band contrast of 14.5 magnitudes at 1”, representing the largest, deepest search for exoplanets by the completion of the survey. The Gemini Planet Imager Exoplanet Survey is in the process of surveying 600 stars, pushing these contrasts to a few tenths of an arcsecond from the star. With the advent of large surveys (many hundreds of stars) using advanced planet-imagers we gain the ability to move beyond measuring the frequency of wide-separation giant planets and to simultaneously determine the distribution as a function of planet mass, semi-major axis, and stellar mass, and so directly test models of planet formation and evolution.
A review is presented of Synchrotron X-ray Topography and KOH etching studies carried out on n type 4H-SiC offcut substrates before and after homo-epitaxial growth to study defect replication and strain relaxation processes and identify the nucleation sources of both interfacial dislocations (IDs) and half-loop arrays (HLAs) which are known to have a deleterious effect on device performance. We show that these types of defects can nucleate during epilayer growth from: (1) short segments of edge oriented basal plane dislocations (BPDs) in the substrate which are drawn by glide into the epilayer; and (2) segments of half loops of BPD that are attached to the substrate surface prior to growth which also glide into the epilayer. It is shown that the initial motion of the short edge oriented BPD segments that are drawn from the substrate into the epilayer is caused by thermal stress resulting from radial temperature gradients experienced by the wafer whilst in the epi-chamber. This same stress also causes the initial glide of the surface half-loop into the epilayer and through the advancing epilayer surface. These mobile BPD segments provide screw oriented segments that pierce the advancing epilayer surface that initially replicate as the crystal grows. Once critical thickness is reached, according to the Mathews-Blakeslee model , these screw segments glide sideways under the action of the mismatch stress leaving IDs and HLAs in their wake. The origin of the mismatch stress is shown to be associated with lattice parameter differences at the growth temperature, arising from the differences in doping concentration between substrate and epilayer.
We report on the analysis of virtual powder-diffraction patterns from serial femtosecond crystallography (SFX) data collected at an X-ray free-electron laser. Different approaches to binning and normalizing these patterns are discussed with respect to the microstructural characteristics which each highlights. Analysis of SFX data from a powder of Pr0.5Ca0.5MnO3 in this way finds evidence of other trace phases in its microstructure which was not detectable in a standard powder-diffraction measurement. Furthermore, a comparison between two virtual powder pattern integration strategies is shown to yield different diffraction peak broadening, indicating sensitivity to different types of microstrain. This paper is a first step in developing new data analysis methods for microstructure characterization from serial crystallography data.
Avian diet selection is hypothesized to be sensitive to seasonal changes in breeding status, but few tests exist for frugivorous tropical birds. Frugivorous birds provide an interesting test case because fruits are relatively deficient in minerals critical for reproduction. Here, we quantify annual patterns of fruit availability and diet for two frugivorous hornbill (Bucerotidae) species over a 5.5-y period to test for patterns of diet selection. Data from the lowland tropical rain forest of the Dja Reserve, Cameroon, are used to generate two nutritional indices. One index estimates the nutrient concentration of the diet chosen by Ceratogymna atrata and Bycanistes albotibialis on a monthly basis using 3165 feeding observations combined with fruit pulp sample data. The second index is an estimate of nutrient concentration of a non-selective or neutral diet across the study area based on tree fruiting phenology, vegetation survey and fruit-pulp sample data. Fifty-nine fruit pulp samples representing 40 species were analysed for 16 nutrient categories to contribute to both indices. Pulp samples accounted for approximately 75% of the observed diets. The results support expected patterns of nutrient selection. The two hornbill species selected a diet rich in calcium during the early breeding season (significantly so for B. albotibialis in July and August). Through the brooding and fledging periods, they switched from a calcium-rich diet to one rich in iron and caloric content as well as supplemental protein in the form of invertebrates. Calcium, the calcium to phosphorus ratio and fat concentration were the strongest predictors of breeding success (significant for calcium and Ca:P for B. albotibialis in June). We conclude that hornbills actively select fruit based on nutritional concentration and mineral concentration and that the indices developed here are useful for assessing frugivore diet over time.
Branched-chain fatty acids (BCFA) are bioactive food components that constitute about 2 % of fatty acids in cows' milk fat. There are few systematic data available on the BCFA content of other foods to estimate dietary intakes. In the present study, we report BCFA distribution and content of fresh and processed foods representing the major foods in the American diet and estimate BCFA intake. BCFA are primarily components of dairy and ruminant food products, and are absent from chicken, pork and salmon. The mean BCFA intake of 500 mg/d was delivered primarily from dairy and beef food products; by comparison, average intake of the widely studied long-chain PUFA EPA and DHA has been estimated to be 100 mg/d. Common adjustments in the diet could double the daily intake of BCFA. The fermented foods sauerkraut and miso had appreciable fractions of BCFA, but, overall, they are low-fat foods providing very small amounts of BCFA in the diet, and other fermented foods did not contain BCFA as might have been expected from the influence of microbial exposure. These data support the quantitative importance of BCFA delivered primarily from dairy and beef food products and highlight the need for research into their effects on health.