333 research outputs found
Unrestricted Termination and Non-Termination Arguments for Bit-Vector Programs
Proving program termination is typically done by finding a well-founded
ranking function for the program states. Existing termination provers typically
find ranking functions using either linear algebra or templates. As such they
are often restricted to finding linear ranking functions over mathematical
integers. This class of functions is insufficient for proving termination of
many terminating programs, and furthermore a termination argument for a program
operating on mathematical integers does not always lead to a termination
argument for the same program operating on fixed-width machine integers. We
propose a termination analysis able to generate nonlinear, lexicographic
ranking functions and nonlinear recurrence sets that are correct for
fixed-width machine arithmetic and floating-point arithmetic Our technique is
based on a reduction from program \emph{termination} to second-order
\emph{satisfaction}. We provide formulations for termination and
non-termination in a fragment of second-order logic with restricted
quantification which is decidable over finite domains. The resulted technique
is a sound and complete analysis for the termination of finite-state programs
with fixed-width integers and IEEE floating-point arithmetic
Epigenetic deregulation of multiple S100 gene family members by differential hypomethylation and hypermethylation events in medulloblastoma
Deregulated expression of genes encoding members of the S100 family of calcium-binding proteins has been associated with the malignant progression of multiple tumour types. Using a pharmacological expression reactivation approach, we screened 16 S100 genes for evidence of epigenetic regulation in medulloblastoma, the most common malignant brain tumour of childhood. Four family members (S100A2, S100A4, S100A6 and S100A10) demonstrated evidence of upregulated expression in multiple medulloblastoma cell lines, following treatment with the DNA methyltransferase inhibitor, 5′-aza-2′-deoxycytidine. Subsequent analysis revealed methylation of critical CpG sites located within these four genes in an extended cell line panel. Assessment of these genes in the non-neoplastic cerebellum (from which medulloblastomas develop) revealed strong somatic methylation affecting S100A2 and S100A4, whereas S100A6 and S100A10 were unmethylated. Assessed against these normal tissue-specific methylation states, S100A6 and S100A10 demonstrated tumour-specific hypermethylation in medulloblastoma primary tumours (5 out of 40 and 4 out of 35, respectively, both 12%) and cell lines (both 7 out of 9, 78%), which was associated with their transcriptional silencing. Moreover, S100A6 hypermethylation was significantly associated with the aggressive large cell/anaplastic morphophenotype (P=0.026). In contrast, pro-metastatic S100A4 displayed evidence of hypomethylation relative to the normal cerebellum in a significant proportion primary tumours (7 out of 41, 17%) and cell lines (3 out of 9, 33%), which was associated with its elevated expression. In summary, these data characterise complex patterns of somatic methylation affecting S100 genes in the normal cerebellum and demonstrate their disruption causing epigenetic deregulation of multiple S100 family members in medulloblastoma development. Epigenetic events affecting S100 genes have potential clinical utility and merit further investigation as molecular biomarkers for this disease
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Improved Upper Limit on the Neutrino Mass from a Direct Kinematic Method by KATRIN.
We report on the neutrino mass measurement result from the first four-week science run of the Karlsruhe Tritium Neutrino experiment KATRIN in spring 2019. Beta-decay electrons from a high-purity gaseous molecular tritium source are energy analyzed by a high-resolution MAC-E filter. A fit of the integrated electron spectrum over a narrow interval around the kinematic end point at 18.57 keV gives an effective neutrino mass square value of (-1.0_{-1.1}^{+0.9})  eV^{2}. From this, we derive an upper limit of 1.1 eV (90% confidence level) on the absolute mass scale of neutrinos. This value coincides with the KATRIN sensitivity. It improves upon previous mass limits from kinematic measurements by almost a factor of 2 and provides model-independent input to cosmological studies of structure formation
Commissioning of the vacuum system of the KATRIN Main Spectrometer
The KATRIN experiment will probe the neutrino mass by measuring the
beta-electron energy spectrum near the endpoint of tritium beta-decay. An
integral energy analysis will be performed by an electro-static spectrometer
(Main Spectrometer), an ultra-high vacuum vessel with a length of 23.2 m, a
volume of 1240 m^3, and a complex inner electrode system with about 120000
individual parts. The strong magnetic field that guides the beta-electrons is
provided by super-conducting solenoids at both ends of the spectrometer. Its
influence on turbo-molecular pumps and vacuum gauges had to be considered. A
system consisting of 6 turbo-molecular pumps and 3 km of non-evaporable getter
strips has been deployed and was tested during the commissioning of the
spectrometer. In this paper the configuration, the commissioning with bake-out
at 300{\deg}C, and the performance of this system are presented in detail. The
vacuum system has to maintain a pressure in the 10^{-11} mbar range. It is
demonstrated that the performance of the system is already close to these
stringent functional requirements for the KATRIN experiment, which will start
at the end of 2016.Comment: submitted for publication in JINST, 39 pages, 15 figure
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