1,215 research outputs found
Use of Bayesian networks to dissect the complexity of genetic disease: application to the Genetic Analysis Workshop 17 simulated data
Complex diseases are often the downstream event of a number of risk factors, including both environmental and genetic variables. To better understand the mechanism of disease onset, it is of great interest to systematically investigate the crosstalk among various risk factors. Bayesian networks provide an intuitive graphical interface that captures not only the association but also the conditional independence and dependence structures among the variables, resulting in sparser relationships between risk factors and the disease phenotype than traditional correlation-based methods. In this paper, we apply a Bayesian network to dissect the complex regulatory relationships among disease traits and various risk factors for the Genetic Analysis Workshop 17 simulated data. We use the Bayesian network as a tool for the risk prediction of disease outcome
Selective scattering between Floquet-Bloch and Volkov states in a topological insulator
The coherent optical manipulation of solids is emerging as a promising way to
engineer novel quantum states of matter. The strong time periodic potential of
intense laser light can be used to generate hybrid photon-electron states.
Interaction of light with Bloch states leads to Floquet-Bloch states which are
essential in realizing new photo-induced quantum phases. Similarly, dressing of
free electron states near the surface of a solid generates Volkov states which
are used to study non-linear optics in atoms and semiconductors. The
interaction of these two dynamic states with each other remains an open
experimental problem. Here we use Time and Angle Resolved Photoemission
Spectroscopy (Tr-ARPES) to selectively study the transition between these two
states on the surface of the topological insulator Bi2Se3. We find that the
coupling between the two strongly depends on the electron momentum, providing a
route to enhance or inhibit it. Moreover, by controlling the light polarization
we can negate Volkov states in order to generate pure Floquet-Bloch states.
This work establishes a systematic path for the coherent manipulation of solids
via light-matter interaction.Comment: 21 pages, 6 figures, final version to appear in Nature Physic
Approximation Techniques for Stochastic Analysis of Biological Systems
There has been an increasing demand for formal methods in the design process
of safety-critical synthetic genetic circuits. Probabilistic model checking
techniques have demonstrated significant potential in analyzing the intrinsic
probabilistic behaviors of complex genetic circuit designs. However, its
inability to scale limits its applicability in practice. This chapter addresses
the scalability problem by presenting a state-space approximation method to
remove unlikely states resulting in a reduced, finite state representation of
the infinite-state continuous-time Markov chain that is amenable to
probabilistic model checking. The proposed method is evaluated on a design of a
genetic toggle switch. Comparisons with another state-of-art tool demonstrates
both accuracy and efficiency of the presented method
Activation of Protein Kinase A and Exchange Protein Directly Activated by cAMP Promotes Adipocyte Differentiation of Human Mesenchymal Stem Cells
Human mesenchymal stem cells are primary multipotent cells capable of differentiating into several cell types including adipocytes when cultured under defined in vitro conditions. In the present study we investigated the role of cAMP signaling and its downstream effectors, protein kinase A (PKA) and exchange protein directly activated by cAMP (Epac) in adipocyte conversion of human mesenchymal stem cells derived from adipose tissue (hMADS). We show that cAMP signaling involving the simultaneous activation of both PKA- and Epac-dependent signaling is critical for this process even in the presence of the strong adipogenic inducers insulin, dexamethasone, and rosiglitazone, thereby clearly distinguishing the hMADS cells from murine preadipocytes cell lines, where rosiglitazone together with dexamethasone and insulin strongly promotes adipocyte differentiation. We further show that prostaglandin I2 (PGI2) may fully substitute for the cAMP-elevating agent isobutylmethylxanthine (IBMX). Moreover, selective activation of Epac-dependent signaling promoted adipocyte differentiation when the Rho-associated kinase (ROCK) was inhibited. Unlike the case for murine preadipocytes cell lines, long-chain fatty acids, like arachidonic acid, did not promote adipocyte differentiation of hMADS cells in the absence of a PPARγ agonist. However, prolonged treatment with the synthetic PPARδ agonist L165041 promoted adipocyte differentiation of hMADS cells in the presence of IBMX. Taken together our results emphasize the need for cAMP signaling in concert with treatment with a PPARγ or PPARδ agonist to secure efficient adipocyte differentiation of human hMADS mesenchymal stem cells
From DNA sequence to application: possibilities and complications
The development of sophisticated genetic tools during the past 15 years have facilitated a tremendous increase of fundamental and application-oriented knowledge of lactic acid bacteria (LAB) and their bacteriophages. This knowledge relates both to the assignments of open reading frames (ORF’s) and the function of non-coding DNA sequences. Comparison of the complete nucleotide sequences of several LAB bacteriophages has revealed that their chromosomes have a fixed, modular structure, each module having a set of genes involved in a specific phase of the bacteriophage life cycle. LAB bacteriophage genes and DNA sequences have been used for the construction of temperature-inducible gene expression systems, gene-integration systems, and bacteriophage defence systems.
The function of several LAB open reading frames and transcriptional units have been identified and characterized in detail. Many of these could find practical applications, such as induced lysis of LAB to enhance cheese ripening and re-routing of carbon fluxes for the production of a specific amino acid enantiomer. More knowledge has also become available concerning the function and structure of non-coding DNA positioned at or in the vicinity of promoters. In several cases the mRNA produced from this DNA contains a transcriptional terminator-antiterminator pair, in which the antiterminator can be stabilized either by uncharged tRNA or by interaction with a regulatory protein, thus preventing formation of the terminator so that mRNA elongation can proceed. Evidence has accumulated showing that also in LAB carbon catabolite repression in LAB is mediated by specific DNA elements in the vicinity of promoters governing the transcription of catabolic operons.
Although some biological barriers have yet to be solved, the vast body of scientific information presently available allows the construction of tailor-made genetically modified LAB. Today, it appears that societal constraints rather than biological hurdles impede the use of genetically modified LAB.
The host metabolite D-serine contributes to bacterial niche specificity through gene selection
Escherichia coli comprise a diverse array of both commensals and niche-specific pathotypes. The ability to cause disease results from both carriage of specific virulence factors and regulatory control of these via environmental stimuli. Moreover, host metabolites further refine the response of bacteria to their environment and can dramatically affect the outcome of the host–pathogen interaction. Here, we demonstrate that the host metabolite, D-serine, selectively affects gene expression in E. coli O157:H7. Transcriptomic profiling showed exposure to D-serine results in activation of the SOS response and suppresses expression of the Type 3 Secretion System (T3SS) used to attach to host cells. We also show that concurrent carriage of both the D-serine tolerance locus (dsdCXA) and the locus of enterocyte effacement pathogenicity island encoding a T3SS is extremely rare, a genotype that we attribute to an ‘evolutionary incompatibility’ between the two loci. This study demonstrates the importance of co-operation between both core and pathogenic genetic elements in defining niche specificity
Synchronization modulation increases transepithelial potentials in MDCK monolayers through Na/K pumps
Peer reviewedPublisher PD
Reaction rates and transport in neutron stars
Understanding signals from neutron stars requires knowledge about the
transport inside the star. We review the transport properties and the
underlying reaction rates of dense hadronic and quark matter in the crust and
the core of neutron stars and point out open problems and future directions.Comment: 74 pages; commissioned for the book "Physics and Astrophysics of
Neutron Stars", NewCompStar COST Action MP1304; version 3: minor changes,
references updated, overview graphic added in the introduction, improvements
in Sec IV.A.
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