1,855 research outputs found
Bounded Model Checking for Probabilistic Programs
In this paper we investigate the applicability of standard model checking
approaches to verifying properties in probabilistic programming. As the
operational model for a standard probabilistic program is a potentially
infinite parametric Markov decision process, no direct adaption of existing
techniques is possible. Therefore, we propose an on-the-fly approach where the
operational model is successively created and verified via a step-wise
execution of the program. This approach enables to take key features of many
probabilistic programs into account: nondeterminism and conditioning. We
discuss the restrictions and demonstrate the scalability on several benchmarks
PrIC3: Property Directed Reachability for MDPs
IC3 has been a leap forward in symbolic model checking. This paper proposes
PrIC3 (pronounced pricy-three), a conservative extension of IC3 to symbolic
model checking of MDPs. Our main focus is to develop the theory underlying
PrIC3. Alongside, we present a first implementation of PrIC3 including the key
ingredients from IC3 such as generalization, repushing, and propagation
Interfering with inflammation: a new strategy to block breast cancer self-renewal and progression?
Two recent studies show that epigenetics and inflammation play a relevant role in the regulation of transformation and cancer cell self-renewal in breast tumours, opening up the possibility that cancer progression can be controlled by interfering with inflammation cascades. Struhl's group showed that transient activation of the Src oncoprotein induces transformation and self-renewal of immortal cells via an epigenetic switch involving NF-κB, Lin28, Let-7 microRNA and IL-6. Concomitantly, Wicha's laboratory developed a strategy to selectively target cancer stem cells, retarding tumour growth and reducing metastasis by blocking the IL-8 receptor CXCR1 using either an inhibitor, repertaxin or a specific blocking antibody
Fake Superpotential for Large and Small Extremal Black Holes
We consider the fist order, gradient-flow, description of the scalar fields
coupled to spherically symmetric, asymptotically flat black holes in extended
supergravities. Using the identification of the fake superpotential with
Hamilton's characteristic function we clarify some of its general properties,
showing in particular (besides reviewing the issue of its duality invariance)
that W has the properties of a Liapunov's function, which implies that its
extrema (associated with the horizon of extremal black holes) are
asymptotically stable equilibrium points of the corresponding first order
dynamical system (in the sense of Liapunov). Moreover, we show that the fake
superpotential W has, along the entire radial flow, the same flat directions
which exist at the attractor point. This allows to study properties of the ADM
mass also for small black holes where in fact W has no critical points at
finite distance in moduli space. In particular the W function for small non-BPS
black holes can always be computed analytically, unlike for the large
black-hole case.Comment: 30 pages, LaTeX source. Discussion on the radial evolution of the
scalar fields, in relation to the symmetries of the W-function, extended.
Table 1 added. Typos correcte
Complete mitochondrial genomes and nuclear ribosomal RNA operons of two species of Diplostomum (Platyhelminthes: Trematoda): a molecular resource for taxonomy and molecular epidemiology of important fish pathogens
© 2015 Brabec et al. This is an Open Access article distributed under the terms of the Creative Commons Attribution License
(http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium,
provided the original work is properly credited. The Creative Commons Public Domain Dedication waiver (http://
creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated. The attached file is the published version of the article
Higgs boson decay into 2 photons in the type~II Seesaw Model
We study the two photon decay channel of the Standard Model-like component of
the CP-even Higgs bosons present in the type II Seesaw Model. The corresponding
cross-section is found to be significantly enhanced in parts of the parameter
space, due to the (doubly-)charged Higgs bosons' virtual
contributions, while all the other Higgs decay channels remain Standard
Model(SM)-like. In other parts of the parameter space (and
) interfere destructively, reducing the two photon branching ratio
tremendously below the SM prediction. Such properties allow to account for any
excess such as the one reported by ATLAS/CMS at GeV if confirmed
by future data; if not, for the fact that a SM-like Higgs exclusion in the
diphoton channel around 114-115 GeV as reported by ATLAS, does not contradict a
SM-like Higgs at LEP(!), and at any rate, for the fact that ATLAS/CMS exclusion
limits put stringent lower bounds on the mass, particularly in
the parameter space regions where the direct limits from same-sign leptonic
decays of do not apply.Comment: 26 pages, 7 figure
Complement-Mediated Virus Infectivity Neutralisation by HLA Antibodies Is Associated with Sterilising Immunity to SIV Challenge in the Macaque Model for HIV/AIDS.
Sterilising immunity is a desired outcome for vaccination against human immunodeficiency virus (HIV) and has been observed in the macaque model using inactivated simian immunodeficiency virus (SIV). This protection was attributed to antibodies specific for cell proteins including human leucocyte antigens (HLA) class I and II incorporated into virions during vaccine and challenge virus preparation. We show here, using HLA bead arrays, that vaccinated macaques protected from virus challenge had higher serum antibody reactivity compared with non-protected animals. Moreover, reactivity was shown to be directed against HLA framework determinants. Previous studies failed to correlate serum antibody mediated virus neutralisation with protection and were confounded by cytotoxic effects. Using a virus entry assay based on TZM-bl cells we now report that, in the presence of complement, serum antibody titres that neutralise virus infectivity were higher in protected animals. We propose that complement-augmented virus neutralisation is a key factor in inducing sterilising immunity and may be difficult to achieve with HIV/SIV Env-based vaccines. Understanding how to overcome the apparent block of inactivated SIV vaccines to elicit anti-envelope protein antibodies that effectively engage the complement system could enable novel anti-HIV antibody vaccines that induce potent, virolytic serological response to be developed
Interferon-inducible gene 202b controls CD8+ T cell-mediated suppression in anti-DNA Ig peptide-treated (NZB × NZW) F1 lupus mice
Administration of an artificial peptide (pConsensus) based on anti-DNA IgG sequences that contain major histocompatibility complex class I and class II T-cell determinants, induces immune tolerance in NZB/NZW F1 female (BWF1) mice. To understand the molecular basis of CD8+ Ti-mediated suppression, we previously performed microarray analysis to identify genes that were differentially expressed following tolerance induction with pCons. CD8+ T cells from mice tolerized with pCons showed more than two-fold increase in Ifi202b mRNA, an interferon inducible gene, versus cells from untolerized mice. Ifi202b expression increased through weeks 1–4 after tolerization and then decreased, reapproaching baseline levels at 6 weeks. In vitro polyclonal activation of tolerized CD8+ T cells significantly increased Ifi202b mRNA expression. Importantly, silencing of Ifi202b abrogated the suppressive capacity of CD8+ Ti cells. This was associated with decreased expression of Foxp3, and decreased gene and protein expression of transforming growth factor (TGF)β and interleukin-2 (IL-2), but not of interferon (IFN)-γ, IL-10, or IL-17. Silencing of another IFN-induced gene upregulated in tolerized CD8+ T cells, IFNAR1, had no effect on the ability of CD8+ T cells to suppress autoantibody production. Our findings indicate a potential role for Ifi202b in the suppressive capacity of peptide-induced regulatory CD8+ Ti cells through effects on the expression of Foxp3 and the synthesis of TGFβ
A dominant-negative effect drives selection of TP53 missense mutations in myeloid malignancies
TP53, which encodes the tumor suppressor p53, is the most frequently mutated gene in human cancer. The selective pressures shaping its mutational spectrum, dominated by missense mutations, are enigmatic, and neomorphic gain-of-function (GOF) activities have been implicated. We used CRISPR-Cas9 to generate isogenic human leukemia cell lines of the most common TP53 missense mutations. Functional, DNA-binding, and transcriptional analyses revealed loss of function but no GOF effects. Comprehensive mutational scanning of p53 single-amino acid variants demonstrated that missense variants in the DNA-binding domain exert a dominant-negative effect (DNE). In mice, the DNE of p53 missense variants confers a selective advantage to hematopoietic cells on DNA damage. Analysis of clinical outcomes in patients with acute myeloid leukemia showed no evidence of GOF for TP53 missense mutations. Thus, a DNE is the primary unit of selection for TP53 missense mutations in myeloid malignancies
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