Early Abatement Research Articles

Metformin Enhances the Anti-Cancer Efficacy of Sorafenib via Suppressing MAPK/ERK/Stat3 Axis in Hepatocellular Carcinoma.

Hepatocellular carcinoma (HCC) incidence, as well as related mortality, has been steadily increasing in the USA and across the globe, partly due to the lack of effective therapeutic options for advanced HCC. Though sorafenib is considered standard-of-care for advanced HCC, it only improves median survival by a few months when compared to placebo. Sorafenib is also associated with several unpleasant side effects that often lead to early abatement of therapy. Here, we investigate whether a combination regimen including low-dose sorafenib and a non-toxic dose of anti-diabetic drug metformin can achieve effective inhibition of HCC. Indeed, combining metformin with low-dose sorafenib inhibited growth, proliferation, migration, and invasion potential of HCC cells. We observed a 5.3- and 1.9-fold increase in sub-G1 population in the combination treatment compared to sorafenib alone. We found that the combination of metformin enhanced the efficacy of sorafenib and inhibited the MAPK/ERK/Stat3 axis. Our in vivo studies corroborated the in vitro findings, and mice harboring HepG2-derived tumors showed effective tumor reduction upon treatment with low-dose sorafenib and metformin combination. This work sheds light on a therapeutic strategy aiming to augment sorafenib efficacy or dose-de-escalation that may prove beneficial in circumventing sorafenib resistance as well as minimizing related side effects.

Modeling myths: OnDICEand dynamic realism in integrated assessment models of climate change mitigation

AbstractWe analyze how stylized Integrated Assessment Models (IAMs), and specifically the widely‐used Dynamic Integrated Climate‐Economy model (DICE), represent the cost of emissions abatement. Many assume temporal independence—that abatement costs in one period are not affected by prior abatement. We contrast this with three dimensions of dynamic realism in emitting systems: (i) inertia, (ii) induced innovation, and (iii) path dependence. We review key evidence from the last quarter century on each of these three components. Studies of stock lifetime, dynamics of diffusion and past transitions suggest typical transition timescales of at least 20–40 years for the bulk emitting systems. The evidence that substantial innovation is induced by both prices and market deployment is unambiguous. Finally, both data and a rapidly growing literature demonstrate substantial path dependence in general, and specifically “carbon lock‐in and lock‐out.” Some stylized models in the past decade have incorporated technology learning, and others have considered inertia, but the combination of these factors is important and not yet evident. More complex hybrid IAMs with technology‐rich energy‐system models incorporate these factors, but their complexity has limited the wider understanding and influence of their underlying insights. Few if any global models fully represent path dependence. We conclude with likely implications drawing upon the empirical and modeling evidence accumulated, including results from extending DICE with a highly stylized representation of such dynamic factors. This suggests that dynamicinterdependencies could multiply several‐fold the optimal level of initial abatement expenditure. This is because early abatement then also directly facilitates subsequent emission savings. The diversity of dynamic linkages across sectors and technologies also implies more nuanced policy than a single global carbon price. Thus, the issues explored in this review can radically change the general policy conclusions drawn from models, which, like DICE, neglect dynamic realism.This article is categorized under:Climate Economics > Aggregation Techniques for Impacts and Mitigation Costs

ClimatePolicy, Uncertainty,and theRole ofTechnologicalInnovation

AbstractWe study how uncertainty about climate change severity affects the relative benefits of early abatement and a portfolio of research and development (R&D) in lowering future abatement costs. Optimal early abatement depends on the curvature of the marginal benefit and marginal abatement cost (MAC) functions and how the uncertain parameter affects marginal benefits. R&D in a particular technology depends on whether uncertainty increases early abatement; whether investment lowersmarginalcosts for that technology; whether R&D lowers theslopeof that technology's MAC function; and the shape of that technology's MAC function. We illustrate, focusing on the role of backstop technologies.

Implications of delayed participation and technology failure for the feasibility, costs, and likelihood of staying below temperature targets—Greenhouse gas mitigation scenarios for the 21st century

The feasibility of limiting greenhouse gas concentrations and associated global mean temperature increase to 2 °C above preindustrial levels has recently attracted considerable scientific and policy attention. Whether or not such low targets can be achieved in the long-term depends on a number of assumptions about, for instance, technological change and the willingness of countries to immediately join a post-Kyoto agreement to limit anthropogenic climate change. As part of the EMF22 international scenarios study, our paper contributes to the ongoing discussion by conducting a scenario analysis in order to examine the influence of these assumptions on the feasibility of a set of radiative forcing targets. We distinguish between “first-best scenarios” with full participation, and “second-best scenarios” with delayed participation of Brazil, China, India, and Russia in 2030 and the rest of Non-Annex I countries after 2050. In addition, we explored the robustness of our “first-best” scenario results by varying the assumptions with regard to availability of key technology clusters. Accounting for the deep uncertainties associated with future global mean temperature change, we conduct a probabilistic assessment and explore the scenario's likelihood for staying below a range of different temperature thresholds. Our results indicate the need for a diverse portfolio of mitigation technologies in order to decarbonize the energy system. Efficiency and enhanced energy conservation play an important role across all scenarios. In addition, carbon capture and storage (CCS) is found to be important for achieving particularly low forcing targets as well as for avoiding pronounced overshoot of the target in the medium-term. Negative emission technologies such as bioenergy with CCS have a strong influence on the timing of mitigation; i.e. without their availability much more early action is needed. According to our analysis, significant delay in the participation of major emitters leads to the unattainability of the most stringent forcing targets. Moreover, delayed participation may lead to excessive additional global mitigation cost that may even exceed the mitigation costs of the most stringent forcing targets in the best case with full participation. We find that for countries that significantly delay their participation, the early gains from postponing mitigation may be offset to a large extent in the long-term, due to the need for more pronounced mitigation later in the century. Linking the radiative forcing targets with temperature change, we find that the chances of staying below certain temperature thresholds may be significantly lower over the course of the century than would be by looking exclusively at 2100. From a policy perspective our results therefore suggest that focusing on early abatement to avoid significant overshoot of concentrations may be as important as the long-term concentration target itself.

European Carbon Prices and Banking Restrictions: Evidence from Phase I (2005-2007)

The price of European Union Allowances (EUAs) has been declining at far lower levels than expected during Phase I (2005-2007). Previous literature identifies among its main explanations over-allocation concerns, early abatement efforts in 2005, and possibly decreasing abatement costs in 2006. We advocate low allowance prices may also be explained by banking restrictions between 2007 and 2008. Based on a Hotelling-CAPM analysis, we provide statistical evidence that the French and Polish decisions to ban banking contribute to the explanation of low EUA Phase I prices. Besides, we provide the first rigorous empirical verification that the cost-of-carry relationship between EUA spot and futures prices for delivery during Phase II does not hold after the enforcement of the inter-period banking restrictions. This situation may be interpreted as a sacrifice of the temporal flexibility offered to industrials in Phase I to correct design inefficiencies, and achieve an efficient price pattern in Phase II.

European Carbon Prices and Banking Restrictions: Evidence from Phase I (2005-2007)

The price of European Union Allowances (EUAs) has been declining at far lower levels than expected during Phase I (2005-2007). Previous literature identifies among its main explanations over-allocation concerns, early abatement efforts in 2005, and possibly decreasing abatement costs in 2006. We advocate low allowance prices may also be explained by banking restrictions between 2007 and 2008, which undermined the ability of the EU ETS to provide an efficient price signal for emissions abatement. Based on a Hotelling-CAPM type analysis, our results suggest EUA spot prices do not meet equilibrium conditions in the intertemporal permits market. We also provide statistical evidence that, during the negotiation of National Allocation Plans for Phase II, the French and Polish decisions to ban banking contribute to the explanation of low EUA Phase I prices. Finally, we provide the first rigorous empirical verification that the cost-of-carry relationship between EUA spot and futures prices for delivery during Phase II does not hold after the enforcement of the inter-period banking restrictions. This situation may be interpreted as a sacrifice of the temporal flexibility offered to industrials in Phase I to give a chance to correct design inefficiencies, and achieve a price pattern leading to effective abatement efforts in Phase II.

Optimal CO2-abatement with Socio-economic Inertia and Induced Technological Change

The impact of induced technological change (ITC) in energy/climate models on the timing of optimal CO2-abatement depends on whether R&D or learning-by-doing (LBD) is the driving force. Bottom-up energy system models employing LBD suggest strong increases in optimal early abatement. In this paper we extend an existing top-down model supporting this view according to the notion that socio-economic inertia interferes with rapid technological change. We derive analytical results concerning the impact of inertia and ITC on optimal initial abatement and show a wide range of numerical simulations to illustrate magnitudes. Inertia now dominates the timing decision on early abatement, such that LBD might even have a negative effect on early abatement and the impact of R&D is limited. However, ITC still reduces costs of stabilizing atmospheric CO2-concentrations considerably.

A Sensitivity Analysis of Timing and Costs of Greenhouse Gas Emission Reductions

This paper analyses the optimal timing and macro-economic costs of carbon emis- sion reductions that mitigate the global average atmospheric temperature increase. We use a macro-economic model in which there are two competing energy sources, fossil-fuelled and non- fossil-fuelled. Technological change is represented endogenously through learning curves, and niche markets exist implying positive demand for the relatively expensive non-fossil-fuelled energy source. Under these conditions, with a temperature increase constraint of 2 ◦ C, early abatement is found to be optimal, and, compared to the results of many existing top-down models, the costs of this strategy prove to be low. We perform an extensive sensitivity analysis of our results regarding the uncertainties that dominate various economic and technological modeling parameters. Uncertainties in the learning rate and the elasticity of substitution between the two different energy sources most significantly affect the robustness of our findings.

Modeling non-CO 2 Greenhouse Gas Abatement

Although emissions of CO2 are the largest anthropogenic contributor to the risks of climate change, other substances are important in the formulation of a cost-effective response. To provide improved facilities for addressing their role, we develop an approach for endogenizing control of these other greenhouse gases within a computable general equilibrium (CGE) model of the world economy. The calculation is consistent with underlying economic production theory. For parameterization it is able to draw on marginal abatement cost (MAC) functions for these gases based on detailed technological descriptions of control options. We apply the method to the gases identified in the Kyoto Protocol: methane (CH4), nitrous oxide (N2O), sulfur hexaflouride (SF6), the perflourocarbons (PFCs), and the hydrofluorocarbons (HFCs). Complete and consistent estimates are provided of the costs of meeting greenhouse-gas reduction targets with a focus on “what” flexibility – i.e., the ability to abate the most cost-effective mix of gases in any period. We find that non-CO2 gases are a crucial component of a cost-effective policy. Because of their high GWPs under current international agreements they would contribute a substantial share of early abatement.

THE KYOTO PROTOCOL- THREATS AND OPPORTUNITIES

In 1997, Australia signed the Kyoto Protocol under which it had been assigned what will become a legally binding emissions cap of 108% of its 1990 emissions. This target may be appropriate for our national circumstances but will be challenging to meet. This paper examines the way Woodside Energy Ltd is addressing the threats and opportunities raised by the Kyoto Protocol.The major risk to Woodside's business arises from the division of the Protocol into Annex B and non-Annex B. Australia is in Annex B, which is composed primarily of developed countries that have assigned emission amounts that will be legally binding when the protocol comes into force and is ratified.Meeting the Australian target and the global greenhouse emission reduction objective will require increasing the substitution of gas into national fuel mixes. Natural gas, including LNG, has the lowest lifecycle emissions of any fossil fuel.The Australian LNG industry is the only major Annex B supplier of LNG to Japan and thus would be at a severe competitive disadvantage if the costs of unilaterally imposed abatement policies and measures were applied to the industry in Australia that were not applied to its international competitors. The LNG industry is seeking differential treatment to alleviate this risk. Woodside has proposed a solution, put forward in this paper, that a scheme be negotiated into the Protocol at CoP6, allowing for the repatriation of credits from the LNG fuel cycle to the exporting country. This would permit fair competition across all LNG exporters.Woodside is keen to undertake its fair share of emission reduction and has already implemented some projects that have been successful in this regard. Further implementation of beyond no regrets projects relies on the Commonwealth resolving the recognition for early action question. A trial framework for making decisions on early abatement projects is described.Woodside is also investigating potential opportunities arising from the Protocol. Progress is reported on early investigation into clean development mechanism (CDM) projects and greenhouse abatement research and development (R&D). Sink enhancement studies are nearly complete and a detailed business case is under preparation.

The timing of CO<SUB align=right>2 emissions reductions: the debate revisited

Almost two years before the Kyoto conference, Wigley et al. (1996) published a paper that claimed not only that delaying emissions reductions would be compatible with eventual stabilization of atmospheric concentrations of CO2, but also that it would be less costly than early abatement. Four arguments were raised in favour of their conclusion. Nevertheless, in Kyoto, policy-makers decided to adopt near-term targets. In this paper, the arguments for and against deferral of emissions reductions are revisited. It is shown that these arguments can not be assessed in the absence of a discussion about the stabilization target. If a low stabilisation target is chosen, then early efforts to abate emissions are necessary, whereas a high stabilisation target (say 650 ppm) does not require much effort over the next couple of decades. Finally, a brief discussion of the way that the arguments in favour of delay were perceived in the policy-making community is provided.