530 research outputs found
A study of blow-ups in the Keller-Segel model of chemotaxis
We study the Keller-Segel model of chemotaxis and develop a composite
particle-grid numerical method with adaptive time stepping which allows us to
accurately resolve singular solutions. The numerical findings (in two
dimensions) are then compared with analytical predictions regarding formation
and interaction of singularities obtained via analysis of the stochastic
differential equations associated with the Keller-Segel model
The Complexity of Graph-Based Reductions for Reachability in Markov Decision Processes
We study the never-worse relation (NWR) for Markov decision processes with an
infinite-horizon reachability objective. A state q is never worse than a state
p if the maximal probability of reaching the target set of states from p is at
most the same value from q, regard- less of the probabilities labelling the
transitions. Extremal-probability states, end components, and essential states
are all special cases of the equivalence relation induced by the NWR. Using the
NWR, states in the same equivalence class can be collapsed. Then, actions
leading to sub- optimal states can be removed. We show the natural decision
problem associated to computing the NWR is coNP-complete. Finally, we ex- tend
a previously known incomplete polynomial-time iterative algorithm to
under-approximate the NWR
Single cell analysis identifies <em>CRLF2</em> rearrangements as both early and late events in Down syndrome and non-Down syndrome acute lymphoblastic leukaemia
Deregulated expression of the type I cytokine receptor, CRLF2, is observed in 5-15% of precursor B-cell acute lymphoblastic leukaemia (B-ALL). We have previously reported the genomic landscape of patients with CRLF2 rearrangements (CRLF2-r) using both whole genome and exome sequencing, which identified a number of potential clonal and sub-clonal genomic alterations. In this study, we aimed to assess when the CRLF2-r; IGH-CRLF2 or P2RY8-CRLF2, arose during the evolution of both Down syndrome-ALL (DS-ALL) and non-DS-ALL. Using fluorescence in situ hybridisation, we were able to track up to four structural variants in single cells from 47 CRLF2-r B-ALL patients, which in association with our multiplex single cell analysis of a further four patients, permitted simultaneous tracking of copy number alterations, structural and single nucleotide variants within individual cells. We observed CRLF2-r arising as both early and late events in DS and non-DS-ALL patients. Parallel evolution of discrete clones was observed in the development of CRLF2-r B-ALL, either involving the CRLF2-r or one of the other tracked abnormalities. In depth single cell analysis identified both linear and branching evolution with early clones harbouring a multitude of abnormalities, including the CRLF2-r in DS-ALL patients
The Influence of Specimen Thickness on the High Temperature Corrosion Behavior of CMSX-4 during Thermal-Cycling Exposure
CMSX-4 is a single-crystalline Ni-base superalloy designed to be used at very high temperatures and high mechanical loadings. Its excellent corrosion resistance is due to external alumina-scale formation, which however can become less protective under thermal-cycling conditions. The metallic substrate in combination with its superficial oxide scale has to be considered as a composite suffering high stresses. Factors like different coefficients of thermal expansion between oxide and substrate during temperature changes or growing stresses affect the integrity of the oxide scale. This must also be strongly influenced by the thickness of the oxide scale and the substrate as well as the ability to relief such stresses, e.g., by creep deformation. In order to quantify these effects, thin-walled specimens of different thickness (t = 100500 lm) were prepared. Discontinuous measurements of their mass changes were carried out under thermal-cycling conditions at a hot dwell temperature of 1100 C up to 300 thermal cycles. Thin-walled specimens revealed a much lower oxide-spallation rate compared to thick-walled specimens, while thinwalled specimens might show a premature depletion of scale-forming elements. In order to determine which of these competetive factor is more detrimental in terms of a component’s lifetime, the degradation by internal precipitation was studied using scanning electron microscopy (SEM) in combination with energy-dispersive X-ray spectroscopy (EDS). Additionally, a recently developed statistical spallation model was applied to experimental data [D. Poquillon and D. Monceau, Oxidation of Metals, 59, 409–431 (2003)]. The model describes the overall mass change by oxide scale spallation during thermal cycling exposure and is a useful simulation tool for oxide scale spallation processes accounting for variations in the specimen geometry. The evolution of the net-mass change vs. the number of thermal cycles seems to be strongly dependent on the sample thickness
The anti-glucocorticoid receptor antibody clone 5E4: raising awareness of unspecific antibody binding
Unspecific antibody binding takes a significant toll on researchers in the form of both the economic burden and the disappointed hopes of promising new therapeutic targets. Despite recent initiatives promoting antibody validation, a uniform approach addressing this issue has not yet been developed. Here, we demonstrate that the anti-glucocorticoid receptor (GR) antibody clone 5E4 predominantly targets two different proteins of approximately the same size, namely AMP deaminase 2 (AMPD2) and transcription intermediary factor 1-beta (TRIM28). This paper is intended to generate awareness of unspecific binding of well-established reagents and advocate the use of more rigorous verification methods to improve antibody quality in the future
Invasive Breast Cancer: Recognition of Molecular Subtypes
Molecular profiling has fundamentally changed our understanding of breast cancer in the last 10 years, by creating a new taxonomy of breast cancers based on the expression patterns of so-called ‘intrinsic genes’. Hierarchical clustering analyses performed on microarray-based gene expression profiles of breast cancers defined distinct breast cancer subgroups (luminal type A/B, HER2-enriched type, basal-like type). Since the initial landmark study by Perou et al., the concept of intrinsic breast cancer subtypes has been corroborated and expanded by several independent research groups. Further studies revealed individual properties of the intrinsic subgroups regarding the clinical course and the responsiveness to chemotherapy. The new gene expression profile-based taxonomy of breast cancer has been enthusiastically embraced by the scientific community and hailed as a major breakthrough on the way to individually tailored therapies. However, validation of the gene signatures in prospective studies is necessary before accepting these new technologies in daily clinical practice. In this review, the current data regarding the intrinsic subtypes and the associated clinical implications as well as the methodology of molecular profiling and possible use of immunohistochemistry in identifying intrinsic subtypes are discussed
Spatial Fingerprints of Community Structure in Human Interaction Network for an Extensive Set of Large-Scale Regions
Human interaction networks inferred from country-wide telephone
activity recordings were recently used to redraw political maps
by projecting their topological partitions into geographical
space. The results showed remarkable spatial cohesiveness of the
network communities and a significant overlap between the
redrawn and the administrative borders. Here we present a
similar analysis based on one of the most popular online social
networks represented by the ties between more than 5.8 million
of its geo-located users. The worldwide coverage of their
measured activity allowed us to analyze the large-scale regional
subgraphs of entire continents and an extensive set of examples
for single countries. We present results for North and South
America, Europe and Asia. In our analysis we used the well-
established method of modularity clustering after an aggregation
of the individual links into a weighted graph connecting equal-
area geographical pixels. Our results show fingerprints of both
of the opposing forces of dividing local conflicts and of
uniting cross-cultural trends of globalization
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