Premature Sister Chromatid Separation Is Poorly Detected by the Spindle Assembly Checkpoint as a Result of System-Level Feedback

Sister chromatid cohesion, mediated by the cohesin complex, is essential for faithful mitosis. Nevertheless, evidence suggests that the surveillance mechanism that governs mitotic fidelity, the spindle assembly checkpoint (SAC), is not robust enough to halt cell division when cohesion loss occurs prematurely. The mechanism behind this poor response is not properly understood. Using developing Drosophila brains, we show that full sister chromatid separation elicits a weak checkpoint response resulting in abnormal mitotic exit after a short delay. Quantitative live-cell imaging approaches combined with mathematical modeling indicate that weak SAC activation upon cohesion loss is caused by weak signal generation. This is further attenuated by several feedback loops in the mitotic signaling network. We propose that multiple feedback loops involving cyclin-dependent kinase 1 (Cdk1) gradually impair error-correction efficiency and accelerate mitotic exit upon premature loss of cohesion. Our findings explain how cohesion defects may escape SAC surveillance.

Maternal separation followed by isolation-housing differentially affects prepulse inhibition of the acoustic startle response in C57BL/6 mice

Exposure to chronic stress is associated with an increased incidence of neuropsychiatric dysfunction. The current study evaluated two competing hypotheses, the cumulative stress and the match/mismatch hypothesis of neuropsychiatric dysfunction, using two paradigms relating to exposure to “stress”: pre-weaning maternal separation and post-weaning isolation-housing. C57BL/6 offspring were reared under four conditions: typical animal facility rearing (AFR, control), early handling (EH, daily 15 min separation from dam), maternal separation (MS, daily 4 hr separation from dam), and maternal and peer separation (MPS, daily 4 hr separation from dam and from littermates). After weaning, mice were either housed socially (2–3/cage) or in isolation (1/cage) and then tested for prepulse inhibition in adulthood. Isolation-housed MPS subjects displayed greater deficits in prepulse inhibition relative to socially-housed MPS subjects while socially-housed AFR subjects displayed greater deficits in prepulse inhibition relative to isolation-housed AFR subjects. The results indicate that these treatment conditions represent a potentially valuable model for evaluating the match/mismatch hypothesis in regards to neuropsychiatric dysfunction.

The Principle of Common Concern and Climate Change

Effective policies combating global warming and incentivising reduction of greenhouse gases face fundamental collective action problems. States defending short term interests avoid international commitments and seek to benefit from measures combating global warming taken elsewhere. The paper explores the potential of Common Concern as an emerging principle of international law, in particular international environmental law, in addressing collective action problems and the global commons. It expounds the contours of the principle, its relationship to common heritage of mankind, to shared and differentiated responsibility and to public goods. It explores its potential to provide the foundations not only for international cooperation, but also to justify, and delimitate at the same time, unilateral action at home and deploying extraterritorial effects in addressing the challenges of global warming and climate change mitigation. As unilateral measures mainly translate into measures of trade policy, the principle of Common Concern is inherently linked and limited by existing legal disciplines in particular of the law of the World Trade Organization.

Higher order elicitability and Osband’s principle

A statistical functional, such as the mean or the median, is called elicitable if there is a scoring function or loss function such that the correct forecast of the functional is the unique minimizer of the expected score. Such scoring functions are called strictly consistent for the functional. The elicitability of a functional opens the possibility to compare competing forecasts and to rank them in terms of their realized scores. In this paper, we explore the notion of elicitability for multi-dimensional functionals and give both necessary and sufficient conditions for strictly consistent scoring functions. We cover the case of functionals with elicitable components, but we also show that one-dimensional functionals that are not elicitable can be a component of a higher order elicitable functional. In the case of the variance, this is a known result. However, an important result of this paper is that spectral risk measures with a spectral measure with finite support are jointly elicitable if one adds the “correct” quantiles. A direct consequence of applied interest is that the pair (Value at Risk, Expected Shortfall) is jointly elicitable under mild conditions that are usually fulfilled in risk management applications.

(Table 1) Sedimentary thicknesses, lithologies, ages, and interpreted paleowater depths for ODP Sites 135-840 and 135-841

The sedimentary succession drilled at Sites 840 and 841 on the Tonga forearc allows the sedimentary evolution of the active margin to be reconstructed since shortly after the initiation of subduction during the mid Eocene. Sedimentation has been dominated by submarine fan deposits, principally volcaniclastic turbidites and mass-flows derived from the volcanic arc. Volcaniclastic sedimentation occurred against a background of pelagic nannofossil sedimentation. A number of upward-fining cycles are recognized and are correlated to regional tectonic events, such as the rifting of the Lau Basin at 5.6 Ma. Episodes of sedimentation dating from 16.0 and 10.0 Ma also correlate well with major falls in eustatic sea level and may be at least partially caused by the resulting enhanced erosion of the arc edifice. The early stages of rifting of the Lau Basin are marked by the formation of a brief hiatus at Site 840 (Horizon A), probably a result of the uplift of the Tonga Platform. Controversy exists as to the degree and timing of the uplift of Site 840 before Lau Basin rifting, with estimates ranging from 2500 to 300 m. Structural information favors a lower value. Breakup of the Tonga Arc during rifting resulted in deposition of dacite-dominated, volcaniclastic mass flows, probably reflecting a maximum in arc volcanism at this time. A pelagic interval at Site 840 suggests that no volcanic arc was present adjacent to the Tonga Platform from 5.0 to 3.0 Ma. This represents the time between separation of the Lau Ridge from the Tonga Platform and the start of activity on the Tofua Arc at 3.0 Ma. The sedimentary successions at both sites provide a record of the arc volcanism despite the reworked nature of the deposits. Probe analyses of volcanic glass grains from Site 840 indicate a consistent low-K tholeiite chemistry from 7.0 Ma to the present, possibly reflecting sediment sourcing from a single volcanic center over long periods of time. Trace and rare-earth-element (REE) analyses of basaltic glass grains indicate that thinning of the arc lithosphere had begun by 7.0 Ma and was the principle cause of a progressive depletion of the high-field-strength (HFSE), REE, and large-ion-lithophile (LILE) elements within the arc magmas before rifting. Magmatic underplating of the Tofua Arc has reversed this trend since that time. Increasing fluid flux from the subducting slab since basin rifting has caused a progressive enrichment in LILEs. Subduction erosion of the underside of the forearc lithosphere has caused continuous subsidence and tilting toward the trench since 37.0 Ma. Enhanced subsidence occurred during rifting of the South Fiji and Lau basins. Collision of the Louisville Ridge with the trench has caused no change in the nature of the sedimentation, but it may have been responsible for up to 300 m of uplift at Site 840.

Treatment of combined sewer overflows by high gradient magnetic separation : on-site testing with mobile pilot plant trailer /

Mode of access: Internet.

Sight-singing from the established notation in a series of lessons and exercises on the tonic principle /

Includes index.

Source separation collection and processing equipment : final report.

"January 1981"--Cover.

Source separation : the community awareness program in Somerville and Marblehead, Massachusetts /

Mode of access: Internet.

Magnetic separation : recovery of saleable iron and steel from municipal solid waste /

Mode of access: Internet.

Study of activated sludge separation by dynamic straining /

Mode of access: Internet.

Oil/water separation : state-of-the-art /

Mode of access: Internet.

The true principle of education : the law of nature, the law of mental development : a new view of the end of juvenile culture, especially as regards the female mind /

Mode of access: Internet.