The closing door of climate targets

Robust evidence from a range of climate–carbon cycle models shows that the maximum warming relative to pre-industrial times caused by the emissions of carbon dioxide is nearly proportional to the total amount of emitted anthropogenic carbon (1, 2). This proportionality is a reasonable approximation for simulations covering many emissions scenarios for the time frame 1750 to 2500 (1). This linear relationship is remarkable given the different complexities of the models and the wide range of emissions scenarios considered. It has direct implications for the possibility of achieving internationally agreed climate targets such as those mentioned in the Copenhagen Accord and the Cancun Agreements (3, 4). Here I explain some of the implications of the linear relationship between peak warming and total cumulative carbon emissions.

Allowable carbon emissions lowered by multiple climate targets

Climate targets are designed to inform policies that would limit the magnitude and impacts of climate change caused by anthropogenic emissions of greenhouse gases and other substances. The target that is currently recognized by most world governments1 places a limit of two degrees Celsius on the global mean warming since preindustrial times. This would require large sustained reductions in carbon dioxide emissions during the twenty-first century and beyond2, 3, 4. Such a global temperature target, however, is not sufficient to control many other quantities, such as transient sea level rise5, ocean acidification6, 7 and net primary production on land8, 9. Here, using an Earth system model of intermediate complexity (EMIC) in an observation-informed Bayesian approach, we show that allowable carbon emissions are substantially reduced when multiple climate targets are set. We take into account uncertainties in physical and carbon cycle model parameters, radiative efficiencies10, climate sensitivity11 and carbon cycle feedbacks12, 13 along with a large set of observational constraints. Within this framework, we explore a broad range of economically feasible greenhouse gas scenarios from the integrated assessment community14, 15, 16, 17 to determine the likelihood of meeting a combination of specific global and regional targets under various assumptions. For any given likelihood of meeting a set of such targets, the allowable cumulative emissions are greatly reduced from those inferred from the temperature target alone. Therefore, temperature targets alone are unable to comprehensively limit the risks from anthropogenic emissions.

Beyond monitoring: After-effects of responding to prospective memory targets

Responding to bivalent stimuli (i.e., stimuli with features relevant for different tasks) slows subsequent performance. In prospective memory research, prospective memory targets can be considered as bivalent stimuli because they typically involve features relevant for both the prospective memory task and the ongoing task. The purpose of this study was to investigate how responding to a prospective memory target slows subsequent performance. In two experiments, we embedded the prospective memory task in a task-switching paradigm and we manipulated the degree of task-set overlap between the prospective memory task and the ongoing task. The results showed consistent after-effects of responding to prospective memory targets. The specific trajectory of the slowing depended on the amount of task-set overlap. These results demonstrate that responding to prospective memory targets results in after-effects, a so far neglected cost on ongoing task performance.

Three-dimensional printing creates models for surgical planning of aortic valve replacement after previous coronary bypass grafting.

PURPOSE Resternotomy for aortic valve replacement in patients with previous coronary artery bypass grafting and an internal mammary artery graft may be a surgical problem. Thus, we are exploring the effect of using rapid prototyping techniques for surgical planning and intraoperative orientation during aortic valve replacement after previous coronary artery bypass grafting (CABG). DESCRIPTION As a proof of concept, we studied a patient who had undergone CABG 5 years earlier. At that time the patient received a left internal mammary artery graft to the left anterior descending artery and a venous graft to the right coronary artery. Now the patient required aortic valve replacement due to symptomatic aortic valve stenosis. The left internal mammary artery bypass and the right coronary artery bypass were patent and showed good flow in the angiography. The patient was examined by 128-slice computed tomography. The image data were visualized and reconstructed. Afterwards, a replica showing the anatomic structures was fabricated using a rapid prototyping machine. EVALUATION Using data derived from 128-slice computed tomography angiography linked to proprietary software, we were able to create three-dimensional reconstructions of the vascular anatomy after the previous CABG. The models were sterilized and taken to the operating theatre for orientation during the surgical procedure. CONCLUSIONS Stereolithographic replicas are helpful for choosing treatment strategies in surgical planning and for intraoperative orientation during reoperations of patients with previous CABG.

Emerging metabolic targets in the therapy of hematological malignancies

During the last decade, the development of anticancer therapies has focused on targeting neoplastic-related metabolism. Cancer cells display a variety of changes in their metabolism, which enable them to satisfy the high bioenergetic and biosynthetic demands for rapid cell division. One of the crucial alterations is referred to as the "Warburg effect", which involves a metabolic shift from oxidative phosphorylation towards the less efficient glycolysis, independent of the presence of oxygen. Although there are many examples of solid tumors having altered metabolism with high rates of glucose uptake and glycolysis, it was only recently reported that this phenomenon occurs in hematological malignancies. This review presents evidence that targeting the glycolytic pathway at different levels in hematological malignancies can inhibit cancer cell proliferation by restoring normal metabolic conditions. However, to achieve cancer regression, high concentrations of glycolytic inhibitors are used due to limited solubility and biodistribution, which may result in toxicity. Besides using these inhibitors as monotherapies, combinatorial approaches using standard chemotherapeutic agents could display enhanced efficacy at eradicating malignant cells. The identification of the metabolic enzymes critical for hematological cancer cell proliferation and survival appears to be an interesting new approach for the targeted therapy of hematological malignancies.

An mRNA-Derived Noncoding RNA Targets and Regulates the Ribosome.

The structural and functional repertoire of small non-protein-coding RNAs (ncRNAs) is central for establishing gene regulation networks in cells and organisms. Here, we show that an mRNA-derived 18-nucleotide-long ncRNA is capable of downregulating translation in Saccharomyces cerevisiae by targeting the ribosome. This 18-mer ncRNA binds to polysomes upon salt stress and is crucial for efficient growth under hyperosmotic conditions. Although the 18-mer RNA originates from the TRM10 locus, which encodes a tRNA methyltransferase, genetic analyses revealed the 18-mer RNA nucleotide sequence, rather than the mRNA-encoded enzyme, as the translation regulator. Our data reveal the ribosome as a target for a small regulatory ncRNA and demonstrate the existence of a yet unkown mechanism of translation regulation. Ribosome-targeted small ncRNAs are found in all domains of life and represent a prevalent but so far largely unexplored class of regulatory molecules.

An mRNA-derived ncRNA targets and regulates the ribosome

Small non-protein-coding RNA (ncRNA) molecules have been recognized recently as major contributors to regulatory networks in controlling gene expression in a highly efficient manner. While the list of validated ncRNAs that regulate crucial cellular processes grows steadily, not a single ncRNA has been identified that directly interacts and regulates the ribosome during protein biosynthesis (with the notable exceptions of 7SL RNA and tmRNA). All of the recently discovered regulatory ncRNAs that act on translation (e.g. microRNAs, siRNAs or antisense RNAs) target the mRNA rather than the ribosome. This is unexpected, given the central position the ribosome plays during gene expression. To investigate whether such a class of regulatory ncRNAs does exist we performed genomic screens for small ribosome-associated RNAs in various model organisms of all three domains [1,2]. Here we focus on the functional characterisation of an 18 nucleotide long ncRNA candidate derived from an open reading frame (ORF) of an annotated S. cerevisiae gene, which encodes a tRNA methyltransferase. Yeast cells lacking this tRNA methyltransferase showed clear growth defects in high salt containing media. Genetic analysis showed that the absence of the mRNA-derived ncRNA rather than the absence of the tRNA methyltransferase activity is responsible for the observed phenotype. Since we performed a screen for small ribosome-associated RNAs we examined the regulatory potential of the synthetic 18mer during translation in vitro and in vivo. Metabolic labeling experiments in the presence of the synthetic 18mer RNA revealed an inhibitory potential on the global protein biosynthesis rate. In vitro translation and northern blot analysis further strengthen the hypothesis, that this RNA is a ribosome-associated regulatory ncRNA. Our studies in pro- and eukaryotic model organisms reveal the ribosome as a novel target for small regulatory ncRNAs in all domains of life. Ribosome-bound ncRNAs are capable of fine tuning translation and might represent a so far largely unexplored class of regulatory ncRNAs.

An application of combinatorial optimization in the printing industry

Offset printing is a common method to produce large amounts of printed matter. We consider a real-world offset printing process that is used to imprint customer-specific designs on napkin pouches. The print- ing technology used yields a number of specific constraints. The planning problem consists of allocating designs to printing-plate slots such that the given customer demand for each design is fulfilled, all technologi- cal and organizational constraints are met and the total overproduction and setup costs are minimized. We formulate this planning problem as a mixed-binary linear program, and we develop a multi-pass matching-based savings heuristic. We report computational results for a set of problem instances devised from real-world data.