11,079 research outputs found
Halo detection via large-scale Bayesian inference
We present a proof-of-concept of a novel and fully Bayesian methodology
designed to detect halos of different masses in cosmological observations
subject to noise and systematic uncertainties. Our methodology combines the
previously published Bayesian large-scale structure inference algorithm, HADES,
and a Bayesian chain rule (the Blackwell-Rao Estimator), which we use to
connect the inferred density field to the properties of dark matter halos. To
demonstrate the capability of our approach we construct a realistic galaxy mock
catalogue emulating the wide-area 6-degree Field Galaxy Survey, which has a
median redshift of approximately 0.05. Application of HADES to the catalogue
provides us with accurately inferred three-dimensional density fields and
corresponding quantification of uncertainties inherent to any cosmological
observation. We then use a cosmological simulation to relate the amplitude of
the density field to the probability of detecting a halo with mass above a
specified threshold. With this information we can sum over the HADES density
field realisations to construct maps of detection probabilities and demonstrate
the validity of this approach within our mock scenario. We find that the
probability of successful of detection of halos in the mock catalogue increases
as a function of the signal-to-noise of the local galaxy observations. Our
proposed methodology can easily be extended to account for more complex
scientific questions and is a promising novel tool to analyse the cosmic
large-scale structure in observations.Comment: 17 pages, 13 figures. Accepted for publication in MNRAS following
moderate correction
Electron Transport through a Molecular Conductor with Center-of-Mass Motion
The linear conductance of a molecular conductor oscillating between two
metallic leads is investigated numerically both for Hubbard interacting and
noninteracting electrons. The molecule-leads tunneling barriers depend on the
molecule displacement from its equilibrium position. The results present an
interesting interference which leads to a conductance dip at the electron-hole
symmetry point, that could be experimentally observable. It is shown that this
dip is caused by the destructive interference between the purely electronic and
phonon-assisted tunneling channels, which are found to carry opposite phases.
When an internal vibrational mode is also active, the electron-hole symmetry is
broken but a Fano-like interference is still observed
Quantum Field Theory of Forward Rates with Stochastic Volatility
In a recent formulation of a quantum field theory of forward rates, the
volatility of the forward rates was taken to be deterministic. The field theory
of the forward rates is generalized to the case of stochastic volatility. Two
cases are analyzed, firstly when volatility is taken to be a function of the
forward rates, and secondly when volatility is taken to be an independent
quantum field. Since volatiltiy is a positive valued quantum field, the full
theory turns out to be an interacting nonlinear quantum field theory in two
dimensions. The state space and Hamiltonian for the interacting theory are
obtained, and shown to have a nontrivial structure due to the manifold moving
with a constant velocity. The no arbitrage condition is reformulated in terms
of the Hamiltonian of the system, and then exactly solved for the nonlinear
interacting case.Comment: 7 Figure
Different Ways of Reading, or Just Making the Right Noises?
What does reading look like? Can learning to read be reduced to the acquisition of a set of isolable skills, or proficiency in reading be equated with the independence of the solitary, silent reader of prose fiction? These conceptions of reading and reading development, which figure strongly in educational policy, may appear to be simple common sense. But both ethnographic data and evidence from literary texts suggest that such paradigms offer, at most, a partial and ahistorical picture of reading. An important dimension, neglected in the dominant paradigms, is the irreducibly social quality of reading practices
On certain other sets of integers
We show that if A is a subset of {1,...,N} containing no non-trivial
three-term arithmetic progressions then |A|=O(N/ log^{3/4-o(1)} N).Comment: 29 pp. Corrected typos. Added definitions for some non-standard
notation and remarks on lower bound
Synthetic DNA immunotherapy in biochemically relapsed prostate cancer
Background: INO-5150 (PSA and PSMA) +/- INO-9012 (IL-12), a synthetic DNA immunotherapy, was assessed for safety, immunogenicity and efficacy in biochemically recurrent prostate cancer patients (pts).
Methods: Phase I, open-label, multi-center study in the US included pts with rising PSA after surgery and/or RT, PSA doubling time (PSADT) \u3e3 months (mos), testosterone \u3e150 ng/dL and no concurrent ADT. Safety, immunogenicity and efficacy (PSA kinetics, PFS) were evaluated in 4 treatment arms of 15 pts each. Arms A: 2mg INO-5150, B: 8.5 mg INO-5150, C: 2mg INO-5150 + 1mg INO-9012 and D: 8.5mg INO-5150 + 1mg INO-9012. Pts received 4 IM doses of vaccine followed by electroporation on day 0, wks 3, 12 and 24 and were followed for 72 wks.
Results: 50/61 (82%) pts completed all visits and treatments were well tolerated with no safety concerns. Median PFS for overall population [N = 61, baseline (D0) PSADT range (mos) 1.5-217.1, median 9.8] and for a subset of pts with D0 PSADT ≤12mos (N = 36) has not yet been reached (FU 3-19 mos). 86% of pts with D0 PSADT ≤12 mos were progression free through 19mos FU. 27 out of 36 (75%) pts with D0 PSADT≤ 12 mos had disease stabilization at wks 27 evidenced by significant improvement in log2PSA change over time (slope) and PSADT from D0 (Slope=0.19 declined to 0.1, PSADT=5.3 improved to 10.1 mos, p = \u3c0.0001). This effect was maintained at wk 72 (Slope=0.09, PSADT=10.6, p = \u3c0.0001). Immunogenicity was observed in 77% (47/61) of pts by multiple immunologic assessments. Patient immunogenicity to INO-5150 as determined by CD38 and Perforin + CD8 T cell immune reactivity correlated with attenuated % PSA rise compared to pts without reactivity (p = 0.05, n = 50).
Conclusions: INO-5150 +/- INO-9012 was safe, well tolerated and immunogenic. Clinical efficacy was observed in the patients with D0 PSADT≤ 12 mos as evidenced by a significant dampening of log2PSA change over time and increased PSADT up to 72 weeks FU. Additional genomic analyses are ongoing to further elucidate the correlation of immunologic efficacy and clinical benefit. (NCT02514213)
Knemidokoptinid (Epidermoptidae: Knemidokoptinae) mite infestation in wild red-crowned parakeets (cyanoramphus novaezelandiae): Correlations between macroscopic and microscopic findings
During a study on health and disease in Red-crowned Parakeets (Cyanoramphus novaezelandiae) on Tiritiri Matangi Island and Little Barrier Island (Hauturu-o-Toi) in New Zealand between 2011 and 2013, an outbreak of feather loss prompted the collection of skin biopsies (n5135) under anesthesia from the head of captured birds. A subset of samples (n57) was frozen to obtain whole specimens for identification of ectoparasites. Mites (range 1–11) were observed in 79/135 (58.5%) skin biopsies, whereas feather loss was only found in 47/142 (33.1%) birds captured during the sampling period. Compact orthokeratotic hyperkeratosis and acanthosis were found in association with mites. Procnemidocoptes janssensi (Acari: Epidermoptidae, Knemidokoptinae) was identified from whole mites obtained from skin biopsies. We describe the presence, pathology, and stages of infestation for knemidokoptinid mange in a wild parrot population in New Zealand. Given the clinical and pathologic changes observed and poor knowledge of the parasite’s New Zealand host and geographic distribution, further work is recommended for this and sympatric parrots, to understand relationships between the host, parasite, environment, and expression of disease. Results from this study reinforce the value of including biopsy samples for the investigation of skin disease in wild birds, particularly to link etiologic agents with pathologic changes
Halo detection via large-scale Bayesian inference
We present a proof-of-concept of a novel and fully Bayesian methodology designed to detect
haloes of different masses in cosmological observations subject to noise and systematic uncertainties.
Our methodology combines the previously published Bayesian large-scale structure
inference algorithm, HAmiltonian Density Estimation and Sampling algorithm (HADES), and
a Bayesian chain rule (the Blackwell–Rao estimator), which we use to connect the inferred
density field to the properties of dark matter haloes. To demonstrate the capability of our
approach, we construct a realistic galaxy mock catalogue emulating the wide-area 6-degree
Field Galaxy Survey, which has a median redshift of approximately 0.05. Application of HADES
to the catalogue provides us with accurately inferred three-dimensional density fields and corresponding
quantification of uncertainties inherent to any cosmological observation. We then
use a cosmological simulation to relate the amplitude of the density field to the probability of
detecting a halo with mass above a specified threshold. With this information, we can sum over
the HADES density field realisations to construct maps of detection probabilities and demonstrate
the validity of this approach within our mock scenario. We find that the probability of
successful detection of haloes in the mock catalogue increases as a function of the signal to
noise of the local galaxy observations. Our proposed methodology can easily be extended to
account for more complex scientific questions and is a promising novel tool to analyse the
cosmic large-scale structure in observations.
Key words: methods: numerical – methods: statistical – galaxies: haloes – galaxies: clusters
Narrative-based computational modelling of the Gp130/JAK/STAT signalling pathway.
BACKGROUND: Appropriately formulated quantitative computational models can support researchers in understanding the dynamic behaviour of biological pathways and support hypothesis formulation and selection by "in silico" experimentation. An obstacle to widespread adoption of this approach is the requirement to formulate a biological pathway as machine executable computer code. We have recently proposed a novel, biologically intuitive, narrative-style modelling language for biologists to formulate the pathway which is then automatically translated into an executable format and is, thus, usable for analysis via existing simulation techniques. RESULTS: Here we use a high-level narrative language in designing a computational model of the gp130/JAK/STAT signalling pathway and show that the model reproduces the dynamic behaviour of the pathway derived by biological observation. We then "experiment" on the model by simulation and sensitivity analysis to define those parameters which dominate the dynamic behaviour of the pathway. The model predicts that nuclear compartmentalisation and phosphorylation status of STAT are key determinants of the pathway and that alternative mechanisms of signal attenuation exert their influence on different timescales. CONCLUSION: The described narrative model of the gp130/JAK/STAT pathway represents an interesting case study showing how, by using this approach, researchers can model biological systems without explicitly dealing with formal notations and mathematical expressions (typically used for biochemical modelling), nevertheless being able to obtain simulation and analysis results. We present the model and the sensitivity analysis results we have obtained, that allow us to identify the parameters which are most sensitive to perturbations. The results, which are shown to be in agreement with existing mathematical models of the gp130/JAK/STAT pathway, serve us as a form of validation of the model and of the approach itself
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