Reply to: 'Tropical cirrus and water vapor: an effective Earth infrared iris feedback?'

In assessing the iris effect suggested by Lindzen et al. (2001), Fu et al. (2002) found that the response of high-level clouds to the sea surface temperature had an effect of reducing the climate sensitivity to external radiative forcing, but the effect was not as strong as LCH found. The approach of FBH to specifying longwave emission and cloud albedos appears to be inappropriate, and the derived cloud optical properties may not have real physical meaning. The cloud albedo calculated by FBH is too large for cirrus clouds and too small for boundary layer clouds, which underestimates the iris effect

Excerpts from the paper: Research Status and Recommendation from the Alaska Workshop on Gravity Waves and Turbulence in the Middle Atmosphere, part 1.3A

Internal gravity waves are disturbances whose intrinsic frequencies k(c - u) are smaller than the Brunt-Vaisala frequency (N). Their importance arises because: they are the major components of the total flow and temperature variability fields of the mesosphere (i.e., shears and lapse rates) and hence constitute the likely sources of turbulence; and they are associated with fluxes of momentum that communicate stresses over large distances. For example, gravity waves exert a drag on the flow in the upper mesosphere. However, in order for gravity waves to exert a net drag on the atmosphere, they must be attenuated. There are two general types of processes that seek to attenuate gravity waves: dissipation and saturation. Dissipation is any process that is effective independent of the wave amplitude, while saturation occurs when certain wave amplitude conditions are met. Radiative damping is an example of dissipation, while convective overturning is an example of saturation. The two processes are not mutually exclusive

Study of the relationship between solar activity and terrestrial weather

Evidence for some connection between weather and solar related phenomena is presented. Historical data of world wide temperature variations with relationship to change in solar luminosity are examined. Several test methods for estimating the statistical significance of such phenomena are discussed in detail

A Combination of Approved Antibodies Overcomes Resistance of Lung Cancer to Osimertinib by Blocking Bypass Pathways.

<b>Purpose:</b> Because of emergence of resistance to osimertinib, a third-generation EGFR tyrosine kinase inhibitor (TKI), no targeted treatments are available for patients with lung cancer who lose sensitivity due to new mutations or bypass mechanisms. We examined in animals and <i>in vitro</i> an alternative therapeutic approach making use of antibodies. <b>Experimental Design:</b> An osimertinib-sensitive animal model of lung cancer, which rapidly develops drug resistance, has been employed. To overcome compensatory hyperactivation of ERK, which we previously reported, an anti-EGFR antibody (cetuximab) was combined with other antibodies, as well as with a subtherapeutic dose of osimertinib, and cancer cell apoptosis was assayed. <b>Results:</b> Our animal studies identified a combination of three clinically approved drugs, cetuximab, trastuzumab (an anti-HER2 mAb), and osimertinib (low dose), as an effective and long-lasting treatment that is able to prevent onset of resistance to osimertinib. A continuous schedule of concurrent treatment was sufficient for effective tumor inhibition and for prevention of relapses. Studies employing cultured cells and analyses of tumor extracts indicated that the combination of two mAbs and a subtherapeutic TKI dose sorted EGFR and HER2 for degradation; cooperatively enhanced apoptosis; inhibited activation of ERK; and reduced abundance of several bypass proteins, namely MET, AXL, and HER3. <b>Conclusions:</b> Our <i>in vitro</i> assays and animal studies identified an effective combination of clinically approved drugs that might overcome resistance to irreversible TKIs in clinical settings. The results we present attribute the long-lasting effect of the drug combination to simultaneous blockade of several well-characterized mechanisms of drug resistance. <i>Clin Cancer Res; 24(22); 5610-21. ©2018 AACR</i> <i>See related commentary by Fan and Yu, p. 5499</i>

The response of the ITCZ to extratropical thermal forcing: Idealized slab-ocean experiments with a GCM

Using a comprehensive atmospheric GCM coupled to a slab mixed layer ocean, experiments are performed to study the mechanism by which displacements of the intertropical convergence zone (ITCZ) are forced from the extratropics. The northern extratropics are cooled and the southern extratropics are warmed by an imposed cross-equatorial flux beneath the mixed layer, forcing a southward shift in the ITCZ. The ITCZ displacement can be understood in terms of the degree of compensation between the imposed oceanic flux and the resulting response in the atmospheric energy transport in the tropics. The magnitude of the ITCZ displacement is very sensitive to a parameter in the convection scheme that limits the entrainment into convective plumes. The change in the convection scheme affects the extratropical-tropical interactions in the model primarily by modifying the cloud response. The results raise the possibility that the response of tropical precipitation to extratropical thermal forcing, important for a variety of problems in climate dynamics (such as the response of the tropics to the Northern Hemisphere ice sheets during glacial maxima or to variations in the Atlantic meridional overturning circulation), may be strongly dependent on cloud feedback. The model configuration described here is suggested as a useful benchmark helping to quantify extratropical-tropical interactions in atmospheric models.open988

What is the climate system able to do ‘on its own’?

The climate of the Earth, like planetary climates in general, is broadly controlled by solar irradiation, planetary albedo and emissivity as well as its rotation rate and distribution of land (with its orography) and oceans. However, the majority of climate fluctuations that affect mankind are internal modes of the general circulation of the atmosphere and the oceans. Some of these modes, such as El Nino-Southern Oscillation (ENSO), are quasi-regular and have some longer-term predictive skill; others like the Arctic and Antarctic Oscillation are chaotic and generally unpredictable beyond a few weeks. Studies using general circulation models indicate that internal processes dominate the regional climate and that some like ENSO events have even distinct global signatures. This is one of the reasons why it is so difficult to separate internal climate processes from external ones caused, for example, by changes in greenhouse gases and solar irradiation. However, the accumulation of the warmest seasons during the latest two decades is lending strong support to the forcing of the greenhouse gases. As models are getting more comprehensive, they show a gradually broader range of internal processes including those on longer time scales, challenging the interpretation of the causes of past and present climate events further

Reflection and Ducting of Gravity Waves Inside the Sun

Internal gravity waves excited by overshoot at the bottom of the convection zone can be influenced by rotation and by the strong toroidal magnetic field that is likely to be present in the solar tachocline. Using a simple Cartesian model, we show how waves with a vertical component of propagation can be reflected when traveling through a layer containing a horizontal magnetic field with a strength that varies with depth. This interaction can prevent a portion of the downward-traveling wave energy flux from reaching the deep solar interior. If a highly reflecting magnetized layer is located some distance below the convection zone base, a duct or wave guide can be set up, wherein vertical propagation is restricted by successive reflections at the upper and lower boundaries. The presence of both upward- and downward-traveling disturbances inside the duct leads to the existence of a set of horizontally propagating modes that have significantly enhanced amplitudes. We point out that the helical structure of these waves makes them capable of generating an alpha-effect, and briefly consider the possibility that propagation in a shear of sufficient strength could lead to instability, the result of wave growth due to over-reflection.Comment: 23 pages, 5 figures. Accepted for publication in Solar Physic

Resonant gravity-wave drag enhancement in linear stratified flow over mountains

High-drag states produced in stratified flow over a 2D ridge and an axisymmetric mountain are investigated using a linear, hydrostatic, analytical model. A wind profile is assumed where the background velocity is constant up to a height z1 and then decreases linearly, and the internal gravity-wave solutions are calculated exactly. In flow over a 2D ridge, the normalized surface drag is given by a closed-form analytical expression, while in flow over an axisymmetric mountain it is given by an expression involving a simple 1D integral. The drag is found to depend on two dimensionless parameters: a dimensionless height formed with z_1, and the Richardson number, Ri, in the shear layer. The drag oscillates as z_1 increases, with a period of half the hydrostatic vertical wavelength of the gravity waves. The amplitude of this modulation increases as Ri decreases. This behaviour is due to wave reflection at z_1. Drag maxima correspond to constructive interference of the upward- and downward-propagating waves in the region z < z_1, while drag minima correspond to destructive interference. The reflection coefficient at the interface z = z_1 increases as Ri decreases. The critical level, z_c, plays no role in the drag amplification. A preliminary numerical treatment of nonlinear effects is presented, where z_c appears to become more relevant, and flow over a 2D ridge qualitatively changes its character. But these effects, and their connection with linear theory, still need to be better understood

A novel role for the interleukin-1 receptor axis in resistance to anti-EGFR therapy

Cetuximab (CTX) is a monoclonal antibody targeting the epidermal growth factor receptor (EGFR), commonly used to treat patients with metastatic colorectal cancer (mCRC). Unfortunately, objective remissions occur only in a minority of patients and are of short duration, with a population of cells surviving the treatment and eventually enabling CTX resistance. Our previous study on CRC xenopatients associated poor response to CTX with increased abundance of a set of pro-inflammatory cytokines, including the interleukins IL-1A, IL-1B and IL-8. Stemming from these observations, our current work aimed to assess the role of IL-1 pathway activity in CTX resistance. We employed a recombinant decoy TRAP IL-1, a soluble protein combining the human immunoglobulin Fc portion linked to the extracellular region of the IL-1-receptor (IL-1R1), able to sequester IL-1 directly from the medium. We generated stable clones expressing and secreting a functional TRAP IL-1 into the culture medium. Our results show that IL-1R1 inhibition leads to a decreased cell proliferation and a dampened MAPK and AKT axes. Moreover, CRC patients not responding to CTX blockage displayed higher levels of IL-1R1 than responsive subjects, and abundant IL-1R1 is predictive of survival in patient datasets specifically for the consensus molecular subtype 1 (CMS1). We conclude that IL-1R1 abundance may represent a therapeutic marker for patients who become refractory to monoclonal antibody therapy, while inhibition of IL-1R1 by TRAP IL-1 may offer a novel therapeutic strategy