315 research outputs found
Numerical Investigation of Installed Jet Noise Sensitivity to Lift and Wing/Engine Positioning
The file attached to this record is the author's final peer reviewed version. The Publisher's final version can be found by following the DOI link.As the turbofan engines of modern transport aircraft have increasingly larger bypass ratios,
by necessity to avoid longer undercarriage, the engine must be installed closer to the wing. This
then has the potential of interaction between the jet flow and a deployed flap. This interaction
can be an important noise source when the high-lift systems are deployed, as at approach and
take-off. Investigating the parameters that have a strong influence on the installation noise
penalty can help in identifying noise reduction measures. In this paper Wall-Modelled Large
Eddy Simulations (WMLES), combined with the FfowcsWilliams and Hawkings (FW-H) sound
extrapolation method, are performed to reproduce three experimental cases, with the aim of
isolating the different contributions of flap angle and trailing-edge/jet-axis distance h. The
first case (DOAK), consisting of a single jet installed near a horizontal flat plate, confirms the
fundamental mechanisms of jet-surface interaction and jet-surface reflection in the absence of
lift. The second case (DLR-F16), with a coaxial jet installed under a high-lift wing, reveals the
trailing-edge/jet-axis distance h as the dominant parameter, with a possible influence of the
flap angle at low frequencies. The third case (SYMPHONY) is used to study the interaction of a
coaxial jet with a full aircraft geometry using Fourier decomposition of the pressure near-field
to analyse the effects on sound sources and radiation
Vamsa: Automated Provenance Tracking in Data Science Scripts
There has recently been a lot of ongoing research in the areas of fairness,
bias and explainability of machine learning (ML) models due to the self-evident
or regulatory requirements of various ML applications. We make the following
observation: All of these approaches require a robust understanding of the
relationship between ML models and the data used to train them. In this work,
we introduce the ML provenance tracking problem: the fundamental idea is to
automatically track which columns in a dataset have been used to derive the
features/labels of an ML model. We discuss the challenges in capturing such
information in the context of Python, the most common language used by data
scientists. We then present Vamsa, a modular system that extracts provenance
from Python scripts without requiring any changes to the users' code. Using 26K
real data science scripts, we verify the effectiveness of Vamsa in terms of
coverage, and performance. We also evaluate Vamsa's accuracy on a smaller
subset of manually labeled data. Our analysis shows that Vamsa's precision and
recall range from 90.4% to 99.1% and its latency is in the order of
milliseconds for average size scripts. Drawing from our experience in deploying
ML models in production, we also present an example in which Vamsa helps
automatically identify models that are affected by data corruption issues
Molecular Assessment of Bacterial Vaginosis by Lactobacillus Abundance and Species Diversity
Background
To date, women are most often diagnosed with bacterial vaginosis (BV) using microscopy based Nugent scoring or Amsel criteria. However, the accuracy is less than optimal. The aim of the present study was to confirm the identity of known BV-associated composition profiles and evaluate indicators for BV using three molecular methods.
Methods
Evaluation of indicators for BV was carried out by 16S rRNA amplicon sequencing of the V5-V7 region, a tailor-made 16S rRNA oligonucleotide-based microarray, and a PCR-based profiling technique termed IS-profiling, which is based on fragment variability of the 16S-23S rRNA intergenic spacer region. An inventory of vaginal bacterial species was obtained from 40 females attending a Dutch sexually transmitted infection outpatient clinic, of which 20 diagnosed with BV (Nugent score 7–10), and 20 BV negative (Nugent score 0–3).
Results
Analysis of the bacterial communities by 16S rRNA amplicon sequencing revealed two clusters in the BV negative women, dominated by either Lactobacillus iners or Lactobacillus crispatus and three distinct clusters in the BV positive women. In the former, there was a virtually complete, negative correlation between L. crispatus and L. iners. BV positive subjects showed cluster profiles that were relatively high in bacterial species diversity and dominated by anaerobic species, including Gardnerella vaginalis, and those belonging to the Families of Lachnospiraceae and Leptotrichiaceae. Accordingly, the Gini-Simpson index of species diversity, and the relative abundance Lactobacillus species appeared consistent indicators for BV. Under the conditions used, only the 16S rRNA amplicon sequencing method was suitable to assess species diversity, while all three molecular composition profiling methods were able to indicate Lactobacillus abundance in the vaginal microbiota.
Conclusion
An affordable and simple molecular test showing a depletion of the genus Lactobacillus in combination with an increased species diversity of vaginal microbiota could serve as an alternative and practical diagnostic method for the assessment of BV
Expansion of voltage-dependent Na+ channel gene family in early tetrapods coincided with the emergence of terrestriality and increased brain complexity
Author Posting. © The Authors, 2010. This is the author's version of the work. It is posted here by permission of Oxford University Press for personal use, not for redistribution. The definitive version was published in Molecular Biology and Evolution 28 (2011): 1415-1424, doi:10.1093/molbev/msq325.Mammals have 10 voltage-dependent sodium (Nav) channel genes. Nav
channels are expressed in different cell types with different sub-cellular
distributions and are critical for many aspects of neuronal processing. The last
common ancestor of teleosts and tetrapods had four Nav channel genes
presumably on four different chromosomes. In the lineage leading to mammals a
series of tandem duplications on two of these chromosomes more than doubled
the number of Nav channel genes. It is unknown when these duplications
occurred, whether they occurred against a backdrop of duplication of flanking
genes on their chromosomes, or as an expansion of ion channel genes in
general. We estimated key dates of the Nav channel gene family expansion by
phylogenetic analysis using teleost, elasmobranch, lungfish, amphibian, avian,
lizard, and mammalian Nav channel sequences, as well as chromosomal synteny
for tetrapod genes. We tested, and exclude, the null hypothesis that Nav
channel genes reside in regions of chromosomes prone to duplication by
demonstrating the lack of duplication or duplicate retention of surrounding genes.
We also find no comparable expansion in other voltage dependent ion channel
gene families of tetrapods following the teleost-tetrapod divergence. We posit a
specific expansion of the Nav channel gene family in the Devonian and
Carboniferous periods when tetrapods evolved, diversified, and invaded the
terrestrial habitat. During this time the amniote forebrain evolved greater
anatomical complexity and novel tactile sensory receptors appeared. The
duplication of Nav channel genes allowed for greater regional specialization in
Nav channel expression, variation in sub-cellular localization, and enhanced
processing of somatosensory input.This work was funded by the
National Science Foundation (IBN 0236147 to H.H.Z and M.C.J), and the
National Institutes of Health (R01GM084879 to H.H.Z)
Isothiocyanates are detected in human synovial fluid following broccoli consumption and can affect the tissues of the knee joint
Osteoarthritis is a major cause of disability and there is no current pharmaceutical treatment which can prevent the disease or slow its progression. Dietary advice or supplementation is clearly an attractive option since it has low toxicity and ease of implementation on a population level. We have previously demonstrated that sulforaphane, a dietary isothiocyanate derived from its glucosinolate precursor which is found in broccoli, can prevent cartilage destruction in cells, in in vitro and in vivo models of osteoarthritis. As the next phase of this research, we enrolled 40 patients with knee osteoarthritis undergoing total knee replacement into a proof-of-principle trial. Patients were randomised to either a low or high glucosinolate diet for 14 days prior to surgery. We detected ITCs in the synovial fluid of the high glucosinolate group, but not the low glucosinolate group. This was mirrored by an increase in ITCs and specifically sulforaphane in the plasma. Proteomic analysis of synovial fluid showed significantly distinct profiles between groups with 125 differentially expressed proteins. The functional consequence of this diet will now be tested in a clinical trial
The consensus molecular subtypes of colorectal cancer
Colorectal cancer (CRC) is a frequently lethal disease with heterogeneous outcomes and drug responses. To resolve inconsistencies among the reported gene expression-based CRC classifications and facilitate clinical translation, we formed an international consortium dedicated to large-scale data sharing and analytics across expert groups. We show marked interconnectivity between six independent classification systems coalescing into four consensus molecular subtypes (CMSs) with distinguishing features: CMS1 (microsatellite instability immune, 14%), hypermutated, microsatellite unstable and strong immune activation; CMS2 (canonical, 37%), epithelial, marked WNT and MYC signaling activation; CMS3 (metabolic, 13%), epithelial and evident metabolic dysregulation; and CMS4 (mesenchymal, 23%), prominent transforming growth factor-beta activation, stromal invasion and angiogenesis. Samples with mixed features (13%) possibly represent a transition phenotype or intratumoral heterogeneity. We consider the CMS groups the most robust classification system currently available for CRC-with clear biological interpretability-and the basis for future clinical stratification and subtype-based targeted interventions
A Threshold Equation for Action Potential Initiation
In central neurons, the threshold for spike initiation can depend on the stimulus and varies between cells and between recording sites in a given cell, but it is unclear what mechanisms underlie this variability. Properties of ionic channels are likely to play a role in threshold modulation. We examined in models the influence of Na channel activation, inactivation, slow voltage-gated channels and synaptic conductances on spike threshold. We propose a threshold equation which quantifies the contribution of all these mechanisms. It provides an instantaneous time-varying value of the threshold, which applies to neurons with fluctuating inputs. We deduce a differential equation for the threshold, similar to the equations of gating variables in the Hodgkin-Huxley formalism, which describes how the spike threshold varies with the membrane potential, depending on channel properties. We find that spike threshold depends logarithmically on Na channel density, and that Na channel inactivation and K channels can dynamically modulate it in an adaptive way: the threshold increases with membrane potential and after every action potential. Our equation was validated with simulations of a previously published multicompartemental model of spike initiation. Finally, we observed that threshold variability in models depends crucially on the shape of the Na activation function near spike initiation (about −55 mV), while its parameters are adjusted near half-activation voltage (about −30 mV), which might explain why many models exhibit little threshold variability, contrary to experimental observations. We conclude that ionic channels can account for large variations in spike threshold
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