120 research outputs found
Oncogenic c-H-ras deregulates survivin expression: An improvement for survival
AbstractSurvivin protein accomplishes two basic functions: cell cycle regulation and control of apoptosis. It is only expressed in G2/M phase and it influences rescue pathways in apoptosis-induced cells. Overexpression of constitutive active c-H-ras in HeLa, or induction of c-H-ras in a stable HeLaDiR cell line, led to sustained survivin expression in all cell cycle phases and even protected cells from drug induced apoptosis. siRNA-mediated silencing of survivin reversed this protection. Here we link the anti-apoptotic property of survivin to its cell cycle (in)dependent regulation via the activity of oncogenic c-H-ras
Alternative Splicing of Fibroblast Growth Factor Receptor IgIII Loops in Cancer
Alternative splicing
of the IgIII loop of fibroblast growth factor
receptors (FGFRs) 1–3 produces b- and
c-variants of the receptors with distinctly
different biological impact based on their
distinct ligand-binding spectrum. Tissue-specific expression of these splice variants
regulates interactions in embryonic development,
tissue maintenance and repair, and cancer.
Alterations in FGFR2 splicing are involved in
epithelial mesenchymal transition that produces
invasive, metastatic features during tumor
progression.
Recent research has elucidated regulatory factors that determine
the splice choice both on the level of exogenous signaling events
and on the RNA-protein interaction level. Moreover, methodology
has been developed that will enable the in depth analysis of
splicing events during tumorigenesis and provide further insight on
the role of FGFR 1–3 IIIb and IIIc in the pathophysiology of
various malignancies. This paper aims to summarize expression
patterns in various tumor types and outlines possibilities for
further analysis and application
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Establishing Flight Software Reliability: Testing, Model Checking, Constraint-Solving, Monitoring and Learning
In this paper we discuss the application of a range of techniques to the
verification of mission-critical flight software at NASA’s Jet Propulsion Laboratory.
For this type of application we want to achieve a higher level of confidence than can
be achieved through standard software testing. Unfortunately, given the current state
of the art, especially when efforts are constrained by the tight deadlines and resource
limitations of a flight project, it is not feasible to produce a rigorous formal proof of
correctness of even a well-specified stand-alone module such as a file system (much less
more tightly coupled or difficult-to-specify modules). This means that we must look for
a practical alternative in the area between traditional testing and proof, as we attempt
to optimize rigor and coverage. The approaches we describe here are based on testing,
model checking, constraint-solving, monitoring, and finite-state machine learning, in
addition to static code analysis. The results we have obtained in the domain of file systems
are encouraging, and suggest that for more complex properties of programs with
complex data structures, it is possibly more beneficial to use constraint solvers to guide
and analyze execution (i.e., as in testing, even if performed by a model checking tool)
than to translate the program and property into a set of constraints, as in abstraction-based
and bounded model checkers. Our experience with non-file-system flight software
modules shows that methods even further removed from traditional static formal methods
can be assisted by formal approaches, yet readily adopted by test engineers and
software developers, even as the key problem shifts from test generation and selection
to test evaluation.Keywords: Verification, Formal proof, Flight software, File systems, Model checking, Testin
Suppression of mutant Kirsten-RAS (KRASG12D)-driven pancreatic carcinogenesis by dual-specificity MAP kinase phosphatases 5 and 6
The cytoplasmic phosphatase DUSP6 and its nuclear counterpart DUSP5 are negative regulators of RAS/ERK signalling. Here we use deletion of either Dusp5 or Dusp6 to explore the roles of these phosphatases in a murine model of KRASG12D-driven pancreatic cancer. By 56-days, loss of either DUSP5 or DUSP6 causes a significant increase in KRASG12D-driven pancreatic hyperplasia. This is accompanied by increased pancreatic acinar to ductal metaplasia (ADM) and the development of pre-neoplastic pancreatic intraepithelial neoplasia (PanINs). In contrast, by 100-days, pancreatic hyperplasia is reversed with significant atrophy of pancreatic tissue and weight loss observed in animals lacking either DUSP5 or DUSP6. On further ageing, Dusp6−/− mice display accelerated development of metastatic pancreatic ductal adenocarcinoma (PDAC), while in Dusp5−/− animals, although PDAC development is increased this process is attenuated by atrophy of pancreatic acinar tissue and severe weight loss in some animals before cancer could progress. Our data suggest that despite a common target in the ERK MAP kinase, DUSP5 and DUSP6 play partially non-redundant roles in suppressing oncogenic KRASG12D signalling, thus retarding both tumour initiation and progression. Our data suggest that loss of either DUSP5 or DUSP6, as observed in certain human tumours, including the pancreas, could promote carcinogenesis
The Electron Capture in Ho Experiment - a Short Update
The definition of the absolute neutrino mass scale is one of the main goals of the Particle Physics today. The study of the end-point regions of the β- and electron capture (EC) spectrum offers a possibility to determine the effective electron (anti-)neutrino mass in a completely model independent way, as it only relies on the energy and momentum conservation.
The ECHo (Electron Capture in 163Ho) experiment has been designed in the attempt to measure the effective mass of the electron neutrino by performing high statistics and high energy resolution measurements of the 163 Ho electron capture spectrum. To achieve this goal, large arrays of low temperature metallic magnetic calorimeters (MMCs) implanted with with 163Ho are used. Here we report on the structure and the status of the experiment
Challenges in QCD matter physics - The Compressed Baryonic Matter experiment at FAIR
Substantial experimental and theoretical efforts worldwide are devoted to
explore the phase diagram of strongly interacting matter. At LHC and top RHIC
energies, QCD matter is studied at very high temperatures and nearly vanishing
net-baryon densities. There is evidence that a Quark-Gluon-Plasma (QGP) was
created at experiments at RHIC and LHC. The transition from the QGP back to the
hadron gas is found to be a smooth cross over. For larger net-baryon densities
and lower temperatures, it is expected that the QCD phase diagram exhibits a
rich structure, such as a first-order phase transition between hadronic and
partonic matter which terminates in a critical point, or exotic phases like
quarkyonic matter. The discovery of these landmarks would be a breakthrough in
our understanding of the strong interaction and is therefore in the focus of
various high-energy heavy-ion research programs. The Compressed Baryonic Matter
(CBM) experiment at FAIR will play a unique role in the exploration of the QCD
phase diagram in the region of high net-baryon densities, because it is
designed to run at unprecedented interaction rates. High-rate operation is the
key prerequisite for high-precision measurements of multi-differential
observables and of rare diagnostic probes which are sensitive to the dense
phase of the nuclear fireball. The goal of the CBM experiment at SIS100
(sqrt(s_NN) = 2.7 - 4.9 GeV) is to discover fundamental properties of QCD
matter: the phase structure at large baryon-chemical potentials (mu_B > 500
MeV), effects of chiral symmetry, and the equation-of-state at high density as
it is expected to occur in the core of neutron stars. In this article, we
review the motivation for and the physics programme of CBM, including
activities before the start of data taking in 2022, in the context of the
worldwide efforts to explore high-density QCD matter.Comment: 15 pages, 11 figures. Published in European Physical Journal
Tick-borne encephalitis virus in dogs - is this an issue?
The last review on Tick-borne encephalitis (TBE) in dogs was published almost ten years ago. Since then, this zoonotic tick-borne arbovirus has been geographically spreading and emerging in many regions in Eurasia and continues to do so. Dogs become readily infected with TBE virus but they are accidental hosts not capable to further spread the virus. They seroconvert upon infection but they seem to be much more resistant to the clinical disease than humans. Apart from their use as sentinels in endemic areas, however, an increasing number of case reports appeared during the last decade thus mirroring the rising public health concerns. Owing to the increased mobility of people travelling to endemic areas with their companion dogs, this consequently leads to problems in recognizing and diagnosing this severe infection in a yet non-endemic area, simply because the veterinarians are not considering TBE. This situation warrants an update on the epidemiology, clinical presentation and possible preventions of TBE in the dog
Emerging Roles of Exosomes in Cancer for Possible Clinical Use
Exosomes are membrane-structured extracellular vesicles (EVs) with nano-scale size that are released from different cell types [...
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