8 research outputs found
Biases in the Experimental Annotations of Protein Function and their Effect on Our Understanding of Protein Function Space
The ongoing functional annotation of proteins relies upon the work of
curators to capture experimental findings from scientific literature and apply
them to protein sequence and structure data. However, with the increasing use
of high-throughput experimental assays, a small number of experimental studies
dominate the functional protein annotations collected in databases. Here we
investigate just how prevalent is the "few articles -- many proteins"
phenomenon. We examine the experimentally validated annotation of proteins
provided by several groups in the GO Consortium, and show that the distribution
of proteins per published study is exponential, with 0.14% of articles
providing the source of annotations for 25% of the proteins in the UniProt-GOA
compilation. Since each of the dominant articles describes the use of an assay
that can find only one function or a small group of functions, this leads to
substantial biases in what we know about the function of many proteins.
Mass-spectrometry, microscopy and RNAi experiments dominate high throughput
experiments. Consequently, the functional information derived from these
experiments is mostly of the subcellular location of proteins, and of the
participation of proteins in embryonic developmental pathways. For some
organisms, the information provided by different studies overlap by a large
amount. We also show that the information provided by high throughput
experiments is less specific than those provided by low throughput experiments.
Given the experimental techniques available, certain biases in protein function
annotation due to high-throughput experiments are unavoidable. Knowing that
these biases exist and understanding their characteristics and extent is
important for database curators, developers of function annotation programs,
and anyone who uses protein function annotation data to plan experiments.Comment: Accepted to PLoS Computational Biology. Press embargo applies. v4:
text corrected for style and supplementary material inserte
The Sudbury Neutrino Observatory
The Sudbury Neutrino Observatory is a second generation water Cherenkov
detector designed to determine whether the currently observed solar neutrino
deficit is a result of neutrino oscillations. The detector is unique in its use
of D2O as a detection medium, permitting it to make a solar model-independent
test of the neutrino oscillation hypothesis by comparison of the charged- and
neutral-current interaction rates. In this paper the physical properties,
construction, and preliminary operation of the Sudbury Neutrino Observatory are
described. Data and predicted operating parameters are provided whenever
possible.Comment: 58 pages, 12 figures, submitted to Nucl. Inst. Meth. Uses elsart and
epsf style files. For additional information about SNO see
http://www.sno.phy.queensu.ca . This version has some new reference
DIII-D research towards establishing the scientific basis for future fusion reactors
DIII-D research is addressing critical challenges in preparation for ITER and the next
generation of fusion devices through focusing on plasma physics fundamentals that underpin
key fusion goals, understanding the interaction of disparate core and boundary plasma
physics, and developing integrated scenarios for achieving high performance fusion regimes.
Fundamental investigations into fusion energy science find that anomalous dissipation of
runaway electrons (RE) that arise following a disruption is likely due to interactions with
RE-driven kinetic instabilities, some of which have been directly observed, opening a new
avenue for RE energy dissipation using naturally excited waves. Dimensionless parameter
scaling of intrinsic rotation and gyrokinetic simulations give a predicted ITER rotation profile
with significant turbulence stabilization. Coherence imaging spectroscopy confirms near
sonic flow throughout the divertor towards the target, which may account for the convectiondominated parallel heat flux. Core-boundary integration studies show that the small angle slot
divertor achieves detachment at lower density and extends plasma cooling across the divertor
target plate, which is essential for controlling heat flux and erosion. The Super H-mode regime
has been extended to high plasma current (2.0 MA) and density to achieve very high pedestal
pressures (~30 kPa) and stored energy (3.2 MJ) with H98y2 â 1.6â2.4. In scenario work, the
ITER baseline Q = 10 scenario with zero injected torque is found to have a fusion gain metric
βĎE independent of current between q95 = 2.8â3.7, and a lower limit of pedestal rotation for
RMP ELM suppression has been found. In the wide pedestal QH-mode regime that exhibits
improved performance and no ELMs, the start-up counter torque has been eliminated so that
the entire discharge uses â0 injected torque and the operating space is more ITER-relevant.
Finally, the high-βN (⊽3.8) hybrid scenario has been extended to the high-density levels
necessary for radiating divertor operation, achieving ~40% divertor heat flux reduction using
either argon or neon with Ptot up to 15 MW.This material is based upon work supported by the U.S.
Department of Energy, Office of Science, Office of Fusion
Energy Sciences, using the DIII-D National Fusion Facility, a
DOE Office of Science user facility, under Awards DE-FC02-
04ER54698. DIII-D data shown in this paper can be obtained
in digital format by following the links at https://fusion.gat.
com/global/D3D_DMP
Gut Microbiome Composition and Metabolic Capacity Differ by <i>FUT2</i> Secretor Status in Exclusively Breastfed Infants
A major polymorphism in the fucosyltransferase2 (FUT2) gene influences risk of multiple gut diseases, but its impact on the microbiome of breastfed infants was unknown. In individuals with an active FUT2 enzyme (âsecretorsâ), the intestinal mucosa is abundantly fucosylated, providing mutualist bacteria with a rich endogenous source of fucose. Non-secretors comprise approximately one-fifth of the population, and they lack the ability to create this enzyme. Similarly, maternal secretor status influences the abundance of a breastfeeding motherâs fucosylated milk oligosaccharides. We compared the impact of maternal secretor status, measured by FUT2 genotype, and infant secretor status, measured by FUT2 genotype and phenotype, on early infant fecal microbiome samples collected from 2-month-old exclusively breastfed infants (n = 59). Infant secretor status (19% non-secretor, 25% low-secretor, and 56% full-secretor) was more strongly associated with the infant microbiome than it was with the maternal FUT2 genotype. Alpha diversity was greater in the full-secretors than in the low- or non-secretor infants (p = 0.049). Three distinct microbial enterotypes corresponded to infant secretor phenotype (p = 0.022) and to the dominance of Bifidobacterium breve, B. longum, or neither (p < 0.001). Infant secretor status was also associated with microbial metabolic capacity, specifically, bioenergetics pathways. We concluded that in exclusively breastfed infants, infantâbut not maternalâsecretor status is associated with infant microbial colonization and metabolic capacity