2,430 research outputs found
Denoising diffusion models for out-of-distribution detection
Out-of-distribution detection is crucial to the safe deployment of machine
learning systems. Currently, unsupervised out-of-distribution detection is
dominated by generative-based approaches that make use of estimates of the
likelihood or other measurements from a generative model. Reconstruction-based
methods offer an alternative approach, in which a measure of reconstruction
error is used to determine if a sample is out-of-distribution. However,
reconstruction-based approaches are less favoured, as they require careful
tuning of the model's information bottleneck - such as the size of the latent
dimension - to produce good results. In this work, we exploit the view of
denoising diffusion probabilistic models (DDPM) as denoising autoencoders where
the bottleneck is controlled externally, by means of the amount of noise
applied. We propose to use DDPMs to reconstruct an input that has been noised
to a range of noise levels, and use the resulting multi-dimensional
reconstruction error to classify out-of-distribution inputs. We validate our
approach both on standard computer-vision datasets and on higher dimension
medical datasets. Our approach outperforms not only reconstruction-based
methods, but also state-of-the-art generative-based approaches. Code is
available at https://github.com/marksgraham/ddpm-ood
Laboratory and Clinical Studies of Cardiac Transplantation
Cardiac transplantation was carried out on four patients at the Medical College of Virginia between May and October of 1968, in an effort to salvage them from the terminal stages of otherwise uncorrectable heart disease. Despite a strikingly good early recovery from operation in each case, three of the patients died of acute homograft rejection in one to three weeks; our second case is living and well, ten months after operation, and is at this writing the world\u27s third longest survivor. The world experience to June of 1969 includes about 130 cardiac transplants. Of the first 100 patients operated on over six months ago, 20 are surviving, and the majority of these have returned to a productive existence, demonstrating the feasibility of complete rehabilitation of at least some terminal patients after cardiac transplantation. The high mortality rate--significantly higher than was anticipated--has resulted from acute and chronic homograft rejection and from the equally difficult problem of infection. Certain lessons have been learned from our own experience and from the world experience with this procedure, and these will be reviewed in an attempt to establish the current status and future potential of cardiac transplantation
Differential effects of apolipoprotein E isoforms on phosphorylation at specific sites on tau by glycogen synthase kinase-3β identified by nano-electrospray mass spectrometry
AbstractPreviously published data have shown an allele-specific variation in the in vitro binding of apolipoprotein E (apoE) to tau, which prompted the hypothesis that apoE binding may protect tau from phosphorylation, apoE3 being more efficient than apoE4. We have, therefore, investigated the effects of apoE on tau phosphorylation in vitro by the proline-directed kinase, glycogen synthase kinase (GSK)-3β. The phosphopeptide maps of tau alone, of tau with apoE3 and of tau with apoE4 were very similar. When apoE2 was present a further four spots were evident. Additionally, of the 15 peptides phosphorylated in the presence or absence of apoE, subtle differences, some isoform-specific, in the relative amounts of phosphorylation were observed
Can segmentation models be trained with fully synthetically generated data?
In order to achieve good performance and generalisability, medical image
segmentation models should be trained on sizeable datasets with sufficient
variability. Due to ethics and governance restrictions, and the costs
associated with labelling data, scientific development is often stifled, with
models trained and tested on limited data. Data augmentation is often used to
artificially increase the variability in the data distribution and improve
model generalisability. Recent works have explored deep generative models for
image synthesis, as such an approach would enable the generation of an
effectively infinite amount of varied data, addressing the generalisability and
data access problems. However, many proposed solutions limit the user's control
over what is generated. In this work, we propose brainSPADE, a model which
combines a synthetic diffusion-based label generator with a semantic image
generator. Our model can produce fully synthetic brain labels on-demand, with
or without pathology of interest, and then generate a corresponding MRI image
of an arbitrary guided style. Experiments show that brainSPADE synthetic data
can be used to train segmentation models with performance comparable to that of
models trained on real data.Comment: 12 pages, 2 (+2 App.) figures, 3 tables. Accepted at Simulation and
Synthesis in Medical Imaging workshop (MICCAI 2022
Synthesis and Antimalarial Activity of Sixteen Dispiro-1,2,4,5-tetraoxanes: Alkyl-Substituted 7,8,15,16-Tetraoxadispiro[5.2.5.2]hexadecanes
Sixteen alkyl-substituted dispiro-1,2,4,5-tetraoxanes (7,8,15,16-tetraoxadispiro[5.2.5.2]hexadecanes) were synthesized to explore dispiro-1,2,4,5-tetraoxane SAR and to identify tetraoxanes with better oral antimalarial activity than prototype tetraoxane 1 (WR 148999). The tetraoxanes were prepared either by peroxidation of the corresponding cyclohexanone derivatives in H2-SO4/CH3CN or by ozonolysis of the corresponding cyclohexanone methyl oximes. Those tetraoxanes with alkyl substituents at the 1 and 10 positions were formed as single stereoisomers, whereas the five tetraoxanes formed without the stereochemical control provided by alkyl groups at the 1 and 10 positions were isolated as mixtures of diastereomers. Three of the sixteen tetraoxanes were inactive (IC50’s \u3e 1000 nM), but five (2, 6, 10, 11, 12) had IC50’s between 10 and 30 nM against the chloroquine-sensitive D6 and chloroquine-resistant W2 clones of Plasmodium falciparum compared to corresponding IC50’s of 55 and 32 nM for 1 and 8.4 and 7.3 nM for artemisinin. We suggest that tetraoxanes 13, 16, and 17 were inactive and tetraoxanes 4 and 7 were weakly active due to steric effects preventing or hindering peroxide bond access to parasite heme. Tetraoxanes 1, 10, 11, and 14, along with artemisinin and arteether as controls, were administered po b.i.d. (128 mg/kg/day) to P. berghei-infected mice on days 3, 4, and 5 post-infection. At this dose, tetraoxanes 10, 11, and 14 cured between 40% and 60% of the infected animals. In comparison, artemisinin and tetraoxane 1 produced no cures, whereas arteether cured 100% of the infected animals. There was no apparent relationship between tetraoxane structure and in vitro neurotoxicity, nor was there any correlation between antimalarial activity and neurotoxicity for these seventeen tetraoxanes
Correlations between in situ denitrification activity and nir-gene abundances in pristine and impacted prairie streams
Denitrification is a process that reduces nitrogen levels in headwaters and other streams. We compared nirS and nirK abundances with the absolute rate of denitrification, the longitudinal coefficient of denitrification (i.e., Kden, which represents optimal denitrification rates at given environmental conditions), and water quality in seven prairie streams to determine if nir-gene abundances explain denitrification activity. Previous work showed that absolute rates of denitrification correlate with nitrate levels; however, no correlation has been found for denitrification efficiency, which we hypothesise might be related to gene abundances. Water-column nitrate and soluble-reactive phosphorus levels significantly correlated with absolute rates of denitrification, but nir-gene abundances did not. However, nirS and nirK abundances significantly correlated with Kden, as well as phosphorus, although no correlation was found between Kden and nitrate. These data confirm that absolute denitrification rates are controlled by nitrate load, but intrinsic denitrification efficiency is linked to nirS and nirK gene abundances
Processing Images from the Zwicky Transient Facility
The Zwicky Transient Facility is a new robotic-observing program, in which a
newly engineered 600-MP digital camera with a pioneeringly large field of view,
47~square degrees, will be installed into the 48-inch Samuel Oschin Telescope
at the Palomar Observatory. The camera will generate ~petabyte of raw
image data over three years of operations. In parallel related work, new
hardware and software systems are being developed to process these data in real
time and build a long-term archive for the processed products. The first public
release of archived products is planned for early 2019, which will include
processed images and astronomical-source catalogs of the northern sky in the
and bands. Source catalogs based on two different methods will be
generated for the archive: aperture photometry and point-spread-function
fitting.Comment: 6 pages, 4 figures, submitted to RTSRE Proceedings (www.rtsre.org
Spectra from the shocked nebulae revealing turbulence near the Galactic Centre
The spectra emitted from clouds near the Galactic Centre are investigated
calculating the UV-optical-IR lines using the physical parameters and the
element abundances constrained by the fit of mid-IR observations. The
characteristic line ratios are compared with those observed in active galaxies.
We have found that the physical conditions in the nebulae near the GC are
different from those of starburst galaxies and AGN, namely, gas velocities and
densities as well as the photoionization fluxes are relatively low. The
geometrical thickness of the emitting nebulae is particularly small suggesting
that matter is strongly fragmented by instabilities leading to an underlying
shock-generated turbulence.Comment: 16 pages, 11 figures, 4 Tables. MNRAS, accepte
Quantification of functionalised gold nanoparticle-targeted knockdown of gene expression in HeLa cells
Introduction: Gene therapy continues to grow as an important area of research, primarily because of its potential in the treatment of disease. One significant area where there is a need for better understanding is in improving the efficiency of oligonucleotide delivery to the cell and indeed, following delivery, the characterization of the effects on the cell. Methods: In this report, we compare different transfection reagents as delivery vehicles for gold nanoparticles functionalized with DNA oligonucleotides, and quantify their relative transfection efficiencies. The inhibitory properties of small interfering RNA (siRNA), single-stranded RNA (ssRNA) and single-stranded DNA (ssDNA) sequences targeted to human metallothionein hMT-IIa are also quantified in HeLa cells. Techniques used in this study include fluorescence and confocal microscopy, qPCR and Western analysis. Findings: We show that the use of transfection reagents does significantly increase nanoparticle transfection efficiencies. Furthermore, siRNA, ssRNA and ssDNA sequences all have comparable inhibitory properties to ssDNA sequences immobilized onto gold nanoparticles. We also show that functionalized gold nanoparticles can co-localize with autophagosomes and illustrate other factors that can affect data collection and interpretation when performing studies with functionalized nanoparticles. Conclusions: The desired outcome for biological knockdown studies is the efficient reduction of a specific target; which we demonstrate by using ssDNA inhibitory sequences targeted to human metallothionein IIa gene transcripts that result in the knockdown of both the mRNA transcript and the target protein
Black holes and Galactic density cusps -- I. Radial orbit cusps and bulges
In this paper, we study the distribution functions that arise naturally
during self-similar radial infall of collisionless matter. Such matter may be
thought of either as stars or as dark matter particles. If a rigorous steady
state is assumed, then the system is infinite and is described by a universal
distribution function given the self-similar index. The steady logarithmic
potential case is exceptional and yields the familiar Gaussian for an infinite
system with an inverse-square density profile. We show subsequently that for
time-dependent radial self-similar infall, the logarithmic case is accurately
described by the Fridmann and Polyachenko distribution function. The system in
this case is finite but growing. We are able to embed a central mass in the
universal steady distribution only by iteration, except in the case of massless
particles. The iteration yields logarithmic corrections to the massless
particle case and requires a `renormalization' of the central mass. A central
spherical mass may be accurately embedded in the Fridmann and Polyachenko
growing distribution however. Some speculation is given concerning the
importance of radial collisionless infall in actual galaxy formation.Comment: 10 pp, 3 fig
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