140 research outputs found
A variational problem on Stiefel manifolds
In their paper on discrete analogues of some classical systems such as the
rigid body and the geodesic flow on an ellipsoid, Moser and Veselov introduced
their analysis in the general context of flows on Stiefel manifolds. We
consider here a general class of continuous time, quadratic cost, optimal
control problems on Stiefel manifolds, which in the extreme dimensions again
yield these classical physical geodesic flows. We have already shown that this
optimal control setting gives a new symmetric representation of the rigid body
flow and in this paper we extend this representation to the geodesic flow on
the ellipsoid and the more general Stiefel manifold case. The metric we choose
on the Stiefel manifolds is the same as that used in the symmetric
representation of the rigid body flow and that used by Moser and Veselov. In
the extreme cases of the ellipsoid and the rigid body, the geodesic flows are
known to be integrable. We obtain the extremal flows using both variational and
optimal control approaches and elucidate the structure of the flows on general
Stiefel manifolds.Comment: 30 page
Conductivity of underdoped YBa2Cu3O7-d : evidence for incoherent pair correlations in the pseudogap regime
Conductivity due to superconducting fluctuations studied in optimally doped
YBa2Cu3O7-d films displays a stronger decay law in temperature than explainable
by theory. A formula is proposed, which fits the data very well with two
superconductive parameters, Tc and the coherence length ksi_c0, and an energy
scale Delta*. This is also valid in underdoped materials and enables to
describe the conductivity up to 300 K with a single-particle excitations
channel in parallel with a channel whose contribution is controlled by ksi_c0,
Tc and Delta*.
This allows to address the nature of the pseudogap in favour of incoherent
pairing.Comment: 14 pages, 4 figures, 1 tabl
A Model Study of Discrete Scale Invariance and Long-Range Interactions
We investigate the modification of discrete scale invariance in the bound
state spectrum by long-range interactions. This problem is relevant for
effective field theory descriptions of nuclear cluster states and
manifestations of the Efimov effect in nuclei. As a model system, we choose a
one dimensional inverse square potential supplemented with a long-range Coulomb
interaction. We study the renormalization and bound-state spectrum of the
system as a function of the Coulomb interaction strength. Our results indicate,
that the counterterm required to renormalize the inverse square potential alone
is sufficient to renormalize the full problem. However, the breaking of the
discrete scale invariance through the Coulomb interaction leads to a modified
bound state spectrum. The shallow bound states are strongly influenced by the
Coulomb interaction while the deep bound states are dominated by the inverse
square potential.Comment: 8 pages, 6 figures, EPJ style, published versio
Low temperature magneto-morphological characterisation of coronene and the resolution of previously observed unexplained phenomena
The polyaromatic hydrocarbon coronene has been the molecule of choice for understanding the physical properties of graphene for over a decade. The modelling of the latter by the former was considered to be valid, as since it was first synthesised in 1932, the physical behaviour of coronene has been determined extremely accurately. We recently discovered however, an unforeseen polymorph of coronene, which exists as an enantiotrope with the previously observed crystal structure. Using low-temperature magnetisation and crystallographic measurements, we show here for the first time that the electronic and magnetic properties of coronene depend directly on the temperature at which it is observed, with hysteretic behaviour exhibited between 300 K and 100 K. Furthermore we determine that this behaviour is a direct result of the appearance and disappearance of the newly-discovered polymorph during thermal cycling. Our results not only highlight the need for theoretical models of graphene to take into account this anomalous behaviour at low temperatures, but also explain puzzling experimental observations of coronene dating back over 40 years
Thiazolidine derivatives as potent and selective inhibitors of the PIM kinase family
The PIM family of serine/threonine kinases have become an attractive target for anti-cancer drug development, particularly for certain hematological malignancies. Here, we describe the discovery of a series of inhibitors of the PIM kinase family using a high throughput screening strategy. Through a combination of molecular modeling and optimization studies, the intrinsic potencies and molecular properties of this series of compounds was significantly improved. An excellent pan-PIM isoform inhibition profile was observed across the series, while optimized examples show good selectivity over other kinases. Two PIM-expressing leukemic cancer cell lines, MV4-11 and K562, were employed to evaluate the in vitro anti-proliferative effects of selected inhibitors. Encouraging activities were observed for many examples, with the best example (44) giving an IC50 of 0.75ÎĽM against the K562 cell line. These data provide a promising starting point for further development of this series as a new cancer therapy through PIM kinase inhibition
The symmetric representation of the rigid body equations and their discretization
This paper analyses continuous and discrete versions of the generalized rigid body equations and the role of these equations in numerical analysis, optimal control and integrable Hamiltonian systems. In particular, we present a symmetric representation of the rigid body equations on the Cartesian product SO(n)×SO(n) and study its associated symplectic structure. We describe the relationship of these ideas with the Moser-Veselov theory of discrete integrable systems and with the theory of variational symplectic integrators. Preliminary work on the ideas discussed in this paper may be found in Bloch et al (Bloch A M, Crouch P, Marsden J E and Ratiu T S 1998 Proc. IEEE Conf. on Decision and Control 37 2249-54).Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/49076/2/no2416.pd
The impact of ENSO on Southern African rainfall in CMIP5 ocean atmosphere coupled climate models
We study the ability of 24 ocean atmosphere global coupled models from the Coupled Model Intercomparison Project 5 (CMIP5) to reproduce the teleconnections between El Niño Southern Oscillation (ENSO) and Southern African rainfall in austral summer using historical forced simulations, with a focus on the atmospheric dynamic associated with El Niño. Overestimations of summer rainfall occur over Southern Africa in all CMIP5 models. Abnormal westward extensions of ENSO patterns are a common feature of all CMIP5 models, while the warming of the Indian Ocean that happens during El Niño is not correctly reproduced. This could impact the teleconnection between ENSO and Southern African rainfall which is represented with mixed success in CMIP5 models. Large-scale anomalies of suppressed deep-convection over the tropical maritime continent and enhanced convection from the central to eastern Pacific are correctly simulated. However, regional biases occur above Africa and the Indian Ocean, particularly in the position of the deep convection anomalies associated with El Niño, which can lead to the wrong sign in rainfall anomalies in the northwest part of South Africa. From the near-surface to mid-troposphere, CMIP5 models underestimate the observed anomalous pattern of pressure occurring over Southern Africa that leads to dry conditions during El Niño years
RNAseq analysis of bronchial epithelial cells to identify COPD-associated genes and SNPs
Abstract
Background
There is a need for more powerful methods to identify low-effect SNPs that contribute to hereditary COPD pathogenesis. We hypothesized that SNPs contributing to COPD risk through cis-regulatory effects are enriched in genes comprised by bronchial epithelial cell (BEC) expression patterns associated with COPD.
Methods
To test this hypothesis, normal BEC specimens were obtained by bronchoscopy from 60 subjects: 30 subjects with COPD defined by spirometry (FEV1/FVC < 0.7, FEV1% < 80%), and 30 non-COPD controls. Targeted next generation sequencing was used to measure total and allele-specific expression of 35 genes in genome maintenance (GM) genes pathways linked to COPD pathogenesis, including seven TP53 and CEBP transcription factor family members. Shrinkage linear discriminant analysis (SLDA) was used to identify COPD-classification models. COPD GWAS were queried for putative cis-regulatory SNPs in the targeted genes.
Results
On a network basis, TP53 and CEBP transcription factor pathway gene pair network connections, including key DNA repair gene ERCC5, were significantly different in COPD subjects (e.g., Wilcoxon rank sum test for closeness, p-value = 5.0E-11). ERCC5 SNP rs4150275 association with chronic bronchitis was identified in a set of Lung Health Study (LHS) COPD GWAS SNPs restricted to those in putative regulatory regions within the targeted genes, and this association was validated in the COPDgene non-hispanic white (NHW) GWAS. ERCC5 SNP rs4150275 is linked (D’ = 1) to ERCC5 SNP rs17655 which displayed differential allelic expression (DAE) in BEC and is an expression quantitative trait locus (eQTL) in lung tissue (p = 3.2E-7). SNPs in linkage (D’ = 1) with rs17655 were predicted to alter miRNA binding (rs873601). A classifier model that comprised gene features CAT, CEBPG, GPX1, KEAP1, TP73, and XPA had pooled 10-fold cross-validation receiver operator characteristic area under the curve of 75.4% (95% CI: 66.3%–89.3%). The prevalence of DAE was higher than expected (p = 0.0023) in the classifier genes.
Conclusions
GM genes comprised by COPD-associated BEC expression patterns were enriched for SNPs with cis-regulatory function, including a putative cis-rSNP in ERCC5 that was associated with COPD risk. These findings support additional total and allele-specific expression analysis of gene pathways with high prior likelihood for involvement in COPD pathogenesis.https://deepblue.lib.umich.edu/bitstream/2027.42/142723/1/12890_2018_Article_603.pd
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