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Cloud feedback mechanisms and their representation in global climate models
Cloud feedback – the change in top-of-atmosphere radiative flux resulting from the cloud response to warming – constitutes by far the largest source of uncertainty in the climate response to CO2 forcing simulated by global climate models (GCMs). We review the main mechanisms for cloud feedbacks, and discuss their representation in climate models and the sources of inter-model spread. Global-mean cloud feedback in GCMs results from three main effects: (1) rising free- tropospheric clouds (a positive longwave effect); (2) decreasing tropical low cloud amount (a positive shortwave effect); (3) increasing high-latitude low cloud optical depth (a negative shortwave effect). These cloud responses simulated by GCMs are qualitatively supported by theory, high-resolution modeling, and observations. Rising high clouds are consistent with the Fixed Anvil Temperature (FAT) hypothesis, whereby enhanced upper-tropospheric radiative cooling causes anvil cloud tops to remain at a nearly fixed temperature as the atmosphere warms. Tropical low cloud amount decreases are driven by a delicate balance between the effects of vertical turbulent fluxes, radiative cooling, large-scale subsidence, and lower-tropospheric stability on the boundary-layer moisture budget. High-latitude low cloud optical depth increases are dominated by phase changes in mixed- phase clouds. The causes of inter-model spread in cloud feedback are discussed, focusing particularly on the role of unresolved parameterized processes such as cloud microphysics, turbulence, and convection
Agency, qualia and life: connecting mind and body biologically
Many believe that a suitably programmed computer could act for its own goals and experience feelings. I challenge this view and argue that agency, mental causation and qualia are all founded in the unique, homeostatic nature of living matter. The theory was formulated for coherence with the concept of an agent, neuroscientific data and laws of physics. By this method, I infer that a successful action is homeostatic for its agent and can be caused by a feeling - which does not motivate as a force, but as a control signal. From brain research and the locality principle of physics, I surmise that qualia are a fundamental, biological form of energy generated in specialized neurons. Subjectivity is explained as thermodynamically necessary on the supposition that, by converting action potentials to feelings, the neural cells avert damage from the electrochemical pulses. In exchange for this entropic benefit, phenomenal energy is spent as and where it is produced - which precludes the objective observation of qualia
Weak and Strong Lensing Statistics
After a brief introduction to gravitational lensing theory, a rough overview
of the types of gravitational lensing statistics that have been performed so
far will be given. I shall then concentrate on recent results of galaxy-galaxy
lensing, which indicate that galactic halos extend much further than can be
probed via rotation of stars and gas.Comment: 10 pages, 2 figures, talk given at the ISSI-Workshop "Matter in the
Universe", 19-23 March 2001 Bern (Switzerland
External sources of clean technology: evidence from the clean development mechanism
New technology is fundamental to sustainable development. However, inventors from industrialized countries often refuse technology transfer because they worry about reverse-engineering. When can clean technology transfer succeed? We develop a formal model of the political economy of North–South technology transfer. According to the model, technology transfer is possible if (1) the technology in focus has limited global commercial potential or (2) the host developing country does not have the capacity to absorb new technologies for commercial use. If both conditions fail, inventors from industrialized countries worry about the adverse competitiveness effects of reverse-engineering, so technology transfer fails. Data analysis of technology transfer in 4,894 projects implemented under the Kyoto Protocol’s Clean Development Mechanism during the 2004–2010 period provides evidence in support of the model
Probing the Universe with Weak Lensing
Gravitational lenses can provide crucial information on the geometry of the
Universe, on the cosmological scenario of formation of its structures as well
as on the history of its components with look-back time. In this review, I
focus on the most recent results obtained during the last five years from the
analysis of the weak lensing regime. The interest of weak lensing as a probe of
dark matter and the for study of the coupling between light and mass on scales
of clusters of galaxies, large scale structures and galaxies is discussed
first. Then I present the impact of weak lensing for the study of distant
galaxies and of the population of lensed sources as function of redshift.
Finally, I discuss the potential interest of weak lensing to constrain the
cosmological parameters, either from pure geometrical effects observed in
peculiar lenses, or from the coupling of weak lensing with the CMB.Comment: To appear Annual Review of Astronomy and Astrophysiscs Vol. 37. Latex
and psfig.sty. Version without figure, 54 pages, 73Kb. Complete version
including 13 figures (60 pages) available on ftp.iap.fr anonymous account in
/pub/from_users/mellier/AnnualReview ; file ARAAmellier.ps.gz 1.6 M
Confirmation of low genetic diversity and multiple breeding females in a social group of Eurasian badgers from microsatellite and field data
The Eurasian badger (
Meles meles
) is a facultatively social carnivore that shows only rudimentary
co-operative behaviour and a poorly defined social hierarchy. Behavioural evidence
and limited genetic data have suggested that more than one female may breed in a
social group. We combine pregnancy detection by ultrasound and microsatellite locus
scores from a well-studied badger population from Wytham Woods, Oxfordshire, UK, to
demonstrate that multiple females reproduce within a social group. We found that at least
three of seven potential mothers reproduced in a group that contained 11 reproductive age
females and nine offspring. Twelve primers showed variability across the species range and only five of these were variable in Wytham. The microsatellites showed a reduced repeat number, a significantly higher number of nonperfect repeats, and moderate heterozygosity
levels in Wytham. The high frequency of imperfect repeats and demographic phenomena might be responsible for the reduced levels of variability observed in the badger
Uniaxial Stress Effects on the Low-Field Magnetoacoustic Interactions in Low and Medium Carbon Steels
In the past, we have shown that the low-field magnetoacoustic technique is capable of detecting uniaxial compression in steel components without necessiating a calibration standard [1,2]. This is because the initial slope of the AF(B)/F curve (fractional frequency change of phase-locked acoustic waves as a function of net magnetic induction) is negative only under compression and positive otherwise, when the specimens are magnetized along the static unaxial stress axis.</p
Suv4-20h Histone Methyltransferases Promote Neuroectodermal Differentiation by Silencing the Pluripotency-Associated Oct-25 Gene
Post-translational modifications (PTMs) of histones exert fundamental roles in regulating gene expression. During development, groups of PTMs are constrained by unknown mechanisms into combinatorial patterns, which facilitate transitions from uncommitted embryonic cells into differentiated somatic cell lineages. Repressive histone modifications such as H3K9me3 or H3K27me3 have been investigated in detail, but the role of H4K20me3 in development is currently unknown. Here we show that Xenopus laevis Suv4-20h1 and h2 histone methyltransferases (HMTases) are essential for induction and differentiation of the neuroectoderm. Morpholino-mediated knockdown of the two HMTases leads to a selective and specific downregulation of genes controlling neural induction, thereby effectively blocking differentiation of the neuroectoderm. Global transcriptome analysis supports the notion that these effects arise from the transcriptional deregulation of specific genes rather than widespread, pleiotropic effects. Interestingly, morphant embryos fail to repress the Oct4-related Xenopus gene Oct-25. We validate Oct-25 as a direct target of xSu4-20h enzyme mediated gene repression, showing by chromatin immunoprecipitaton that it is decorated with the H4K20me3 mark downstream of the promoter in normal, but not in double-morphant, embryos. Since knockdown of Oct-25 protein significantly rescues the neural differentiation defect in xSuv4-20h double-morphant embryos, we conclude that the epistatic relationship between Suv4-20h enzymes and Oct-25 controls the transit from pluripotent to differentiation-competent neural cells. Consistent with these results in Xenopus, murine Suv4-20h1/h2 double-knockout embryonic stem (DKO ES) cells exhibit increased Oct4 protein levels before and during EB formation, and reveal a compromised and biased capacity for in vitro differentiation, when compared to normal ES cells. Together, these results suggest a regulatory mechanism, conserved between amphibians and mammals, in which H4K20me3-dependent restriction of specific POU-V genes directs cell fate decisions, when embryonic cells exit the pluripotent state
Recurrent hemarthrosis after total knee arthroplasty
This report describes a case of spontaneous recurrent hemarthrosis of the knee that presented 4 weeks after total knee arthroplasty. Femoral arteriography showed a false aneurysm of a branch of the inferior lateral geniculate artery. Therapeutic embolization of the arterial branch was performed using three platinum coils with good clinical result and good knee joint function. Hemarthrosis has not recurred since embolization
Preclinical and clinical biomarker studies of CT1812: A novel approach to Alzheimer's disease modification
INTRODUCTION: Amyloid beta (Aβ) oligomers are one of the most toxic structural forms of the Aβ protein and are hypothesized to cause synaptotoxicity and memory failure as they build up in Alzheimer's disease (AD) patients' brain tissue. We previously demonstrated that antagonists of the sigma-2 receptor complex effectively block Aβ oligomer toxicity. CT1812 is an orally bioavailable, brain penetrant small molecule antagonist of the sigma-2 receptor complex that appears safe and well tolerated in healthy elderly volunteers. We tested CT1812's effect on Aβ oligomer pathobiology in preclinical AD models and evaluated CT1812's impact on cerebrospinal fluid (CSF) protein biomarkers in mild to moderate AD patients in a clinical trial (ClinicalTrials.gov NCT02907567). METHODS: Experiments were performed to measure the impact of CT1812 versus vehicle on Aβ oligomer binding to synapses in vitro, to human AD patient post mortem brain tissue ex vivo, and in living APPSwe /PS1dE9 transgenic mice in vivo. Additional experiments were performed to measure the impact of CT1812 versus vehicle on Aβ oligomer-induced deficits in membrane trafficking rate, synapse number, and protein expression in mature hippocampal/cortical neurons in vitro. The impact of CT1812 on cognitive function was measured in transgenic Thy1 huAPPSwe/Lnd+ and wild-type littermates. A multicenter, double-blind, placebo-controlled parallel group trial was performed to evaluate the safety, tolerability, and impact on protein biomarker expression of CT1812 or placebo given once daily for 28 days to AD patients (Mini-Mental State Examination 18-26). CSF protein expression was measured by liquid chromatography with tandem mass spectrometry or enzyme-linked immunosorbent assay in samples drawn prior to dosing (Day 0) and at end of dosing (Day 28) and compared within each patient and between pooled treated versus placebo-treated dosing groups. RESULTS: CT1812 significantly and dose-dependently displaced Aβ oligomers bound to synaptic receptors in three independent preclinical models of AD, facilitated oligomer clearance into the CSF, increased synaptic number and protein expression in neurons, and improved cognitive performance in transgenic mice. CT1812 significantly increased CSF concentrations of Aβ oligomers in AD patient CSF, reduced concentrations of synaptic proteins and phosphorylated tau fragments, and reversed expression of many AD-related proteins dysregulated in CSF. DISCUSSION: These preclinical studies demonstrate the novel disease-modifying mechanism of action of CT1812 against AD and Aβ oligomers. The clinical results are consistent with preclinical data and provide evidence of target engagement and impact on fundamental disease-related signaling pathways in AD patients, supporting further development of CT1812
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