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Rapid adjustments--the response of meteorology to external forcing while sea surface temperatures (SST) and sea ice are held fixed--can affect the midlatitude circulation and contribute to long-term forced circulation responses in climate simulations. This study examines rapid adjustments in the Southern Hemisphere (SH) circulation using nine models from the Precipitation Driver and Response Model Intercomparison Project (PDRMIP), which perform fixed SST and coupled ocean experiments for five perturbations: a doubling of carbon dioxide (2xCO2), a tripling of methane (3xCH4), a fivefold increase in sulfate aerosol (5xSO4), a tenfold increase in black carbon aerosol (10xBC), and a 2%increase in solar constant (2%Sol). In the coupled experiments, the SH eddy-driven jet shifts poleward and strengthens for forcings that produce global warming (and vice versa for 5xSO4), with the strongest response found in austral summer. In austral winter, the responses project more strongly onto a change in jet strength. For 10xBC, which induces strong shortwave absorption, the multimodel mean (MMM) rapid adjustment in DJF jet latitude is ;75% of the change in the coupled simulations. For the other forcings, which induce larger SST changes, the effect of SST-mediated feedbacks on the SH circulation is larger than the rapid adjustment. Nevertheless, for these perturbations the magnitude of the MMM jet shift due to the rapid adjustment is still around 20%-30% of that in the coupled experiments. The results demonstrate the need to understand the mechanisms for rapid adjustments in the midlatitude circulation, in addition to the effect of changing SSTs. [ABSTRACT FROM AUTHOR]

Quantifying the efficacy of different climate forcings is important for understanding the real‐world climate sensitivity. This study presents a systematic multimodel analysis of different climate driver efficacies using simulations from the Precipitation Driver and Response Model Intercomparison Project (PDRMIP). Efficacies calculated from instantaneous radiative forcing deviate considerably from unity across forcing agents and models. Effective radiative forcing (ERF) is a better predictor of global mean near‐surface air temperature (GSAT) change. Efficacies are closest to one when ERF is computed using fixed sea surface temperature experiments and adjusted for land surface temperature changes using radiative kernels. Multimodel mean efficacies based on ERF are close to one for global perturbations of methane, sulfate, black carbon, and insolation, but there is notable intermodel spread. We do not find robust evidence that the geographic location of sulfate aerosol affects its efficacy. GSAT is found to respond more slowly to aerosol forcing than CO2 in the early stages of simulations. Despite these differences, we find that there is no evidence for an efficacy effect on historical GSAT trend estimates based on simulations with an impulse response model, nor on the resulting estimates of climate sensitivity derived from the historical period. However, the considerable intermodel spread in the computed efficacies means that we cannot rule out an efficacy‐induced bias of ±0.4 K in equilibrium climate sensitivity to CO2 doubling when estimated using the historical GSAT trend. Plain Language Summary: Does the climate respond in the same way to carbon dioxide as it does to methane or aerosol changes? The simple way of thinking about forcing and response in the Earth system assumes that it does, such that, a Watt per square meter forcing from CO2 has the same response as an equivalent forcing from aerosols. Recent work has suggested that this might not be true and that differences in how effective different forcings are at increasing surface temperature (their efficacy) may account for a low estimate of climate sensitivity when examining historical change. We show this all depends on how you estimate your Watts per meter squared forcing in the first place. Using the effective radiative forcing concept to estimate forcing strength makes temperature changes far more predictable, and a lot of these issues with efficacy variation are not as pronounced as they were with earlier definitions. Key Points: Multimodel mean efficacies computed using effective radiative forcing are close to one for major anthropogenic drivers, but there is notable intermodel spreadSurface temperature‐driven radiative feedbacks are generally not constant through time across forcing experimentsPDRMIP results suggest that the efficacy impact on equilibrium climate sensitivity derived from the historical period is limited to ±0.4 °C or better [ABSTRACT FROM AUTHOR]

The response of the hydrological cycle to climate forcings can be understood within the atmospheric energy budget framework. In this study precipitation and energy budget responses to five forcing agents are analyzed using 10 climate models from the Precipitation Driver Response Model Intercomparison Project (PDRMIP). Precipitation changes are split into a forcing-dependent fast response and a temperature-driven hydrological sensitivity. Globally, when normalized by top-of-atmosphere (TOA) forcing, fast precipitation changes are most sensitive to strongly absorbing drivers (CO2, black carbon). However, over land fast precipitation changes are most sensitive to weakly absorbing drivers (sulfate, solar) and are linked to rapid circulation changes. Despite this, land-mean fast responses to CO2 and black carbon exhibit more intermodel spread. Globally, the hydrological sensitivity is consistent across forcings, mainly associated with increased longwave cooling, which is highly correlated with intermodel spread. The land-mean hydrological sensitivity is weaker, consistent with limited moisture availability. The PDRMIP results are used to construct a simple model for land-mean and sea-mean precipitation change based on sea surface temperature change and TOA forcing. The model matches well with CMIP5 ensemble mean historical and future projections, and is used to understand the contributions of different drivers. During the twentieth century, temperature-driven intensification of land-mean precipitation has been masked by fast precipitation responses to anthropogenic sulfate and volcanic forcing, consistent with the small observed trend. However, as projected sulfate forcing decreases, and warming continues, land-mean precipitation is expected to increase more rapidly, and may become clearly observable by the mid-twenty-first century. [ABSTRACT FROM AUTHOR]

Abstract: Future projections of east Amazonian precipitation indicate drying, but they are uncertain and poorly understood. In this study we analyze the Amazonian precipitation response to individual atmospheric forcings using a number of global climate models. Black carbon is found to drive reduced precipitation over the Amazon due to temperature‐driven circulation changes, but the magnitude is uncertain. CO2 drives reductions in precipitation concentrated in the east, mainly due to a robustly negative, but highly variable in magnitude, fast response. We find that the physiological effect of CO2 on plant stomata is the dominant driver of the fast response due to reduced latent heating and also contributes to the large model spread. Using a simple model, we show that CO2 physiological effects dominate future multimodel mean precipitation projections over the Amazon. However, in individual models temperature‐driven changes can be large, but due to little agreement, they largely cancel out in the model mean. [ABSTRACT FROM AUTHOR]

The article focuses on the Precipitation Driver and Response Model Intercomparison Project's (PDRMIP) protocol and preliminary results. The fast precipitation response is more complex due to the changes in atmospheric circulation. Rapid circulation changes in response to forcing are related with the change in atmospheric absorption, as well as the rapid land surface response.

We sought to explore the utility of the verification trial to confirm individual attainment of 'true' VO2max in altitude-residing, endurance-trained runners during treadmill exercise. 24 elite endurance-trained men and women runners (age = 21.5±3.3yr, ht-174.8±9.3cm, body mass = 60.5±6.7 kg, PR 800 m 127.5 ±13.1 s) completed a graded exercise test (GXT) trial (VO2max = 60.C±5.8mL⋅ kg-11⋅min-1), and returned 20min after incremental exercise to complete a verification trial (VO2max = 59.6±5.7mL⋅kg-1⋅ min-1) of constant load, supramaximal exercise. The incidence of 'true' V02max confirmation using the verification trial was 24/24 (100%) with all participants revealing differences in VO2max ≤3% (the technical error of our equipment) between the GXT and verification trials. These findings support use of the verification trial to confirm VO2 max attainment in altitude-residing, endurance-trained runners. [ABSTRACT FROM AUTHOR]

The PPM1D gene is aberrantly amplified in a range of common cancers and encodes a protein phosphatase that is a potential therapeutic target. However, the issue of whether inhibition of PPM1D in human tumour cells that overexpress this protein compromises their viability has not yet been fully addressed. We show here, using an RNA interference (RNAi) approach, that inhibition of PPM1D can indeed reduce the viability of human tumour cells and that this effect is selective; tumour cell lines that overexpress PPM1D are sensitive to PPM1D inhibition whereas cell lines with normal levels are not. Loss of viability associated with PPM1D RNAi in human tumour cells occurs via the activation of the kinase P38. To identify chemical inhibitors of PPM1D, a high-throughput screening of a library of small molecules was performed. This strategy successfully identified a compound that selectively reduces viability of human tumour cell lines that overexpress PPM1D. As expected of a specific inhibitor, the toxicity to PPM1D overexpressing cell lines after inhibitor treatment is P38 dependent. These results further validate PPM1D as a therapeutic target and identify a proof-of-principle small molecule inhibitor.Oncogene (2008) 27, 1036–1044; doi:10.1038/sj.onc.1210729; published online 13 August 2007 [ABSTRACT FROM AUTHOR]

Transcriptional targeting is an important aspect of developing gene therapy vectors in order to restrict transgene expression to selected target cells. One approach, when using retroviral vectors, is to replace viral transcriptional control elements within the long terminal repeat (LTR) with sequences imparting the desired specificity. We have developed such hybrid LTR retroviruses, incorporating sequences from each of the human promoters for flt-1, ICAM-2 and KDR, as part of our antivascular cancer gene therapy strategy targeting tumour endothelial cells. The chosen fragments were used to replace the enhancer or combined enhancer and proximal promoter regions of the viral LTR. All showed activity in primary human breast microvascular endothelial cells, with viruses incorporating ICAM-2 sequences exhibiting the greatest specificity versus nonendothelial cells in vitro and a marked alteration of specificity towards endothelial cells in a subcutaneous xenograft model in vivo. Moreover, our study documents the effect of enhancer and/or proximal promoter deletion on LTR activity and reports that differential dependence in different cell lines can give the false impression of specificity if experiments are not adequately controlled. This finding also has implications for other retroviral vector designs seeking to provide transcriptional specificity and for their safety with respect to prevention of gene activation at sites of proviral integration.Gene Therapy (2004) 11, 775-783. doi:10.1038/sj.gt.3302220 Published online 4 March 2004 [ABSTRACT FROM AUTHOR]

We present the global and regional hydrological sensitivity (HS) to surface temperature changes, for perturbations to CO2, CH4, sulfate and black carbon concentrations, and solar irradiance. Based on results from ten climate models, we show how modeled global mean precipitation increases by 2–3% per kelvin of global mean surface warming, independent of driver, when the effects of rapid adjustments are removed. Previously reported differences in response between drivers are therefore mainly ascribable to rapid atmospheric adjustment processes. All models show a sharp contrast in behavior over land and over ocean, with a strong surface temperature-driven (slow) ocean HS of 3–5%/K, while the slow land HS is only 0–2%/K. Separating the response into convective and large-scale cloud processes, we find larger inter-model differences, in particular over land regions. Large-scale precipitation changes are most relevant at high latitudes, while the equatorial HS is dominated by convective precipitation changes. Black carbon stands out as the driver with the largest inter-model slow HS variability, and also the strongest contrast between a weak land and strong sea response. We identify a particular need for model investigations and observational constraints on convective precipitation in the Arctic, and large-scale precipitation around the Equator. Climate change: Global warming increases rainfall most over oceans Global warming leads to more rain – but little of the change occurs over land. An international team of researchers, led by Bjørn H. Samset at the Norwegian CICERO Center for Climate Research, used ten global climate models to study how precipitation changes when just one factor in the climate system was allowed to change at a time. While models tend to give very different predictions of future rainfall for realistic scenarios, changes due solely to greenhouse gases, aerosols, or the amount of incoming sunlight, give clearer results. Overall, the amount of rain over oceans increases by 4% per degree Celsius, no matter what caused the surface warming. Over land, the increase is only 1–2%. This difference helps explain why observed rainfall changes over land have so far been modest. [ABSTRACT FROM AUTHOR]