3,477 research outputs found
Lung cancer tumorigenicity and drug resistance are maintained through ALDH(hi)CD44(hi) tumor initiating cells
published_or_final_versio
A Replicating Modified Vaccinia Tiantan Strain Expressing an Avian-Derived Influenza H5N1 Hemagglutinin Induce Broadly Neutralizing Antibodies and Cross-Clade Protective Immunity in Mice
published_or_final_versio
Whole genome methylation array reveals the down-regulation of IGFBP6 and SATB2 by HIV-1
published_or_final_versio
The MDM2–p53–pyruvate carboxylase signalling axis couples mitochondrial metabolism to glucose-stimulated insulin secretion in pancreatic β-cells
published_or_final_versio
UNCLES: Method for the identification of genes differentially consistently co-expressed in a specific subset of datasets
Background: Collective analysis of the increasingly emerging gene expression datasets are required. The recently proposed binarisation of consensus partition matrices (Bi-CoPaM) method can combine clustering results from multiple datasets to identify the subsets of genes which are consistently co-expressed in all of the provided datasets in a tuneable manner. However, results validation and parameter setting are issues that complicate the design of such methods. Moreover, although it is a common practice to test methods by application to synthetic datasets, the mathematical models used to synthesise such datasets are usually based on approximations which may not always be sufficiently representative of real datasets. Results: Here, we propose an unsupervised method for the unification of clustering results from multiple datasets using external specifications (UNCLES). This method has the ability to identify the subsets of genes consistently co-expressed in a subset of datasets while being poorly co-expressed in another subset of datasets, and to identify the subsets of genes consistently co-expressed in all given datasets. We also propose the M-N scatter plots validation technique and adopt it to set the parameters of UNCLES, such as the number of clusters, automatically. Additionally, we propose an approach for the synthesis of gene expression datasets using real data profiles in a way which combines the ground-truth-knowledge of synthetic data and the realistic expression values of real data, and therefore overcomes the problem of faithfulness of synthetic expression data modelling. By application to those datasets, we validate UNCLES while comparing it with other conventional clustering methods, and of particular relevance, biclustering methods. We further validate UNCLES by application to a set of 14 real genome-wide yeast datasets as it produces focused clusters that conform well to known biological facts. Furthermore, in-silico-based hypotheses regarding the function of a few previously unknown genes in those focused clusters are drawn. Conclusions: The UNCLES method, the M-N scatter plots technique, and the expression data synthesis approach will have wide application for the comprehensive analysis of genomic and other sources of multiple complex biological datasets. Moreover, the derived in-silico-based biological hypotheses represent subjects for future functional studies.The National Institute for Health Research (NIHR) under its Programme Grants for Applied Research
Programme (Grant Reference Number RP-PG-0310-1004)
Paradigm of tunable clustering using binarization of consensus partition matrices (Bi-CoPaM) for gene discovery
Copyright @ 2013 Abu-Jamous et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits
unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.Clustering analysis has a growing role in the study of co-expressed genes for gene discovery. Conventional binary and fuzzy clustering do not embrace the biological reality that some genes may be irrelevant for a problem and not be assigned to a cluster, while other genes may participate in several biological functions and should simultaneously belong to multiple clusters. Also, these algorithms cannot generate tight clusters that focus on their cores or wide clusters that overlap and contain all possibly relevant genes. In this paper, a new clustering paradigm is proposed. In this paradigm, all three eventualities of a gene being exclusively assigned to a single cluster, being assigned to multiple clusters, and being not assigned to any cluster are possible. These possibilities are realised through the primary novelty of the introduction of tunable binarization techniques. Results from multiple clustering experiments are aggregated to generate one fuzzy consensus partition matrix (CoPaM), which is then binarized to obtain the final binary partitions. This is referred to as Binarization of Consensus Partition Matrices (Bi-CoPaM). The method has been tested with a set of synthetic datasets and a set of five real yeast cell-cycle datasets. The results demonstrate its validity in generating relevant tight, wide, and complementary clusters that can meet requirements of different gene discovery studies.National Institute for Health Researc
Observation of a ppb mass threshoud enhancement in \psi^\prime\to\pi^+\pi^-J/\psi(J/\psi\to\gamma p\bar{p}) decay
The decay channel
is studied using a sample of events collected
by the BESIII experiment at BEPCII. A strong enhancement at threshold is
observed in the invariant mass spectrum. The enhancement can be fit
with an -wave Breit-Wigner resonance function with a resulting peak mass of
and a
narrow width that is at the 90% confidence level.
These results are consistent with published BESII results. These mass and width
values do not match with those of any known meson resonance.Comment: 5 pages, 3 figures, submitted to Chinese Physics
A transient homotypic interaction model for the influenza A virus NS1 protein effector domain
Influenza A virus NS1 protein is a multifunctional virulence factor consisting of an RNA binding domain (RBD), a short linker, an effector domain (ED), and a C-terminal 'tail'. Although poorly understood, NS1 multimerization may autoregulate its actions. While RBD dimerization seems functionally conserved, two possible apo ED dimers have been proposed (helix-helix and strand-strand). Here, we analyze all available RBD, ED, and full-length NS1 structures, including four novel crystal structures obtained using EDs from divergent human and avian viruses, as well as two forms of a monomeric ED mutant. The data reveal the helix-helix interface as the only strictly conserved ED homodimeric contact. Furthermore, a mutant NS1 unable to form the helix-helix dimer is compromised in its ability to bind dsRNA efficiently, implying that ED multimerization influences RBD activity. Our bioinformatical work also suggests that the helix-helix interface is variable and transient, thereby allowing two ED monomers to twist relative to one another and possibly separate. In this regard, we found a mAb that recognizes NS1 via a residue completely buried within the ED helix-helix interface, and which may help highlight potential different conformational populations of NS1 (putatively termed 'helix-closed' and 'helix-open') in virus-infected cells. 'Helix-closed' conformations appear to enhance dsRNA binding, and 'helix-open' conformations allow otherwise inaccessible interactions with host factors. Our data support a new model of NS1 regulation in which the RBD remains dimeric throughout infection, while the ED switches between several quaternary states in order to expand its functional space. Such a concept may be applicable to other small multifunctional proteins
Experimental observation of topological Fermi arcs in type-II Weyl semimetal MoTe2
Weyl semimetal is a new quantum state of matter [1-12] hosting the condensed
matter physics counterpart of relativisticWeyl fermion [13] originally
introduced in high energy physics. The Weyl semimetal realized in the TaAs
class features multiple Fermi arcs arising from topological surface states [10,
11, 14-16] and exhibits novel quantum phenomena, e.g., chiral anomaly induced
negative mag-netoresistance [17-19] and possibly emergent supersymmetry [20].
Recently it was proposed theoretically that a new type (type-II) of Weyl
fermion [21], which does not have counterpart in high energy physics due to the
breaking of Lorentz invariance, can emerge as topologically-protected touching
between electron and hole pockets. Here, we report direct spectroscopic
evidence of topological Fermi arcs in the predicted type-II Weyl semimetal
MoTe2 [22-24]. The topological surface states are confirmed by directly
observing the surface states using bulk-and surface-sensitive angle-resolved
photoemission spectroscopy (ARPES), and the quasi-particle interference (QPI)
pattern between the two putative Fermi arcs in scanning tunneling microscopy
(STM). Our work establishes MoTe2 as the first experimental realization of
type-II Weyl semimetal, and opens up new opportunities for probing novel
phenomena such as exotic magneto-transport [21] in type-II Weyl semimetals.Comment: submitted on 01/29/2016. Nature Physics, in press. Spectroscopic
evidence of the Fermi arcs from two complementary surface sensitive probes -
ARPES and STS. A comparison of the calculated band structure for T_d and 1T'
phase to identify the topological Fermi arcs in the T_d phase is also
included in the supplementary informatio
Isomer Spectroscopy of Neutron-rich 165,167Tb
Open Access JournalWe present information on the excited states in the prolate-deformed, neutron-rich nuclei 165;167Tb100;102. The nuclei of interest were synthesized following in-flight fission of a 345 MeV per nucleon 238U primary beam on a 2 mm 9Be target at the Radioactive Ion-Beam Factory (RIBF), RIKEN, Japan. The exotic nuclei were separated and identified event-by-event using the BigRIPS separator, with discrete energy gamma-ray decays from isomeric states with half-lives in the _s regime measured using the EURICA gamma-ray spectrometer. Metastable-state decays are identified in 165Tb and 167Tb and interpreted as arising from hindered E1 decay from the 7/2-[523] single quasi-proton Nilsson configuration to rotational states built on the 3/2-[411] single quasi-proton ground state. These data correspond to the first spectroscopic information in the heaviest, odd-A terbium isotopes reported to date and provide information on proton Nilsson configurations which reside close to the Fermi surface as the 170Dy doubly-midshell nucleus is approached.postprin
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