13,045 research outputs found
Activation of mammalian Chk1 during DNA replication arrest: a role for Chk1 in the intra-S phase checkpoint monitoring replication origin firing
Checkpoints maintain order and fidelity in the cell cycle by blocking late-occurring events when earlier events are improperly executed. Here we describe evidence for the participation of Chk1 in an intra-S phase checkpoint in mammalian cells. We show that both Chk1 and Chk2 are phosphorylated and activated in a caffeine-sensitive signaling pathway during S phase, but only in response to replication blocks, not during normal S phase progression. Replication block–induced activation of Chk1 and Chk2 occurs normally in ataxia telangiectasia (AT) cells, which are deficient in the S phase response to ionizing radiation (IR). Resumption of synthesis after removal of replication blocks correlates with the inactivation of Chk1 but not Chk2. Using a selective small molecule inhibitor, cells lacking Chk1 function show a progressive change in the global pattern of replication origin firing in the absence of any DNA replication. Thus, Chk1 is apparently necessary for an intra-S phase checkpoint, ensuring that activation of late replication origins is blocked and arrested replication fork integrity is maintained when DNA synthesis is inhibited
Using the UM dynamical cores to reproduce idealised 3D flows
We demonstrate that both the current (New Dynamics), and next generation
(ENDGame) dynamical cores of the UK Met Office global circulation model, the
UM, reproduce consistently, the long-term, large-scale flows found in several
published idealised tests. The cases presented are the Held-Suarez test, a
simplified model of Earth (including a stratosphere), and a hypothetical
tidally locked Earth. Furthermore, we show that using simplifications to the
dynamical equations, which are expected to be justified for the physical
domains and flow regimes we have studied, and which are supported by the
ENDGame dynamical core, also produces matching long-term, large-scale flows.
Finally, we present evidence for differences in the detail of the planetary
flows and circulations resulting from improvements in the ENDGame formulation
over New Dynamics.Comment: 34 Pages, 23 Figures. Accepted for publication in Geoscientific Model
Development (pre-proof version
The design of aircraft using the decision support problem technique
The Decision Support Problem Technique for unified design, manufacturing and maintenance is being developed at the Systems Design Laboratory at the University of Houston. This involves the development of a domain-independent method (and the associated software) that can be used to process domain-dependent information and thereby provide support for human judgment. In a computer assisted environment, this support is provided in the form of optimal solutions to Decision Support Problems
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