Potential consequences of climate change on crop production can be studied using mechanistic crop simulation models. While a broad variety of maize simulation models exist, it is not known whether different models diverge on grain yield responses to changes in climatic factors, or whether they agree in their general trends related to phenology, growth, and yield. With the goal of analyzing the sensitivity of simulated yields to changes in temperature and atmospheric carbon dioxide concentrations [CO2 ], we present the largest maize crop model intercomparison to date, including 23 different models. These models were evaluated for four locations representing a wide range of maize production conditions in the world: Lusignan (France), Ames (USA), Rio Verde (Brazil) and Morogoro (Tanzania). While individual models differed considerably in absolute yield simulation at the four sites, an ensemble of a minimum number of models was able to simulate absolute yields accurately at the four sites even with low data for calibration, thus suggesting that using an ensemble of models has merit. Temperature increase had strong negative influence on modeled yield response of roughly -0.5 Mg ha(-1) per °C. Doubling [CO2 ] from 360 to 720 μmol mol(-1) increased grain yield by 7.5% on average across models and the sites. That would therefore make temperature the main factor altering maize yields at the end of this century. Furthermore, there was a large uncertainty in the yield response to [CO2 ] among models. Model responses to temperature and [CO2 ] did not differ whether models were simulated with low calibration information or, simulated with high level of calibration information.

The objective of this study was to clarify whether the neutrophil-lymphocyte ratio (NLR) and the platelet-lymphocyte ratio (PLR) are significant prognostic markers in patients with resectable colorectal cancer (CRC). A total of 200 patients who underwent curative resection for CRC were enrolled. The NLR and PLR were positively correlated (p < 0.001). Both the NLR and PLR were shown to be good prognostic biomarkers of overall survival (OS) (p=0.002 and p=0.001, respectively). The PLR was an independent prognostic factor of OS based on multivariate analysis (hazard ratio, 1.971; 95% confidence interval, 1.102-3.335; p=0.021).

Advances in genetic engineering tools have contributed to the development of strategies for utilizing biologically derived vesicles as nanomedicines for achieving cell-specific drug delivery. Here, we describe bioengineered bacterial outer membrane vesicles (OMVs) with low immunogenicity that can target and kill cancer cells in a cell-specific manner by delivering small interfering RNA (siRNA) targeting kinesin spindle protein (KSP). A mutant Escherichia coli strain that exhibits reduced endotoxicity toward human cells was engineered to generate OMVs displaying a human epidermal growth factor receptor 2 (HER2)-specific affibody in the membrane as a targeting ligand. Systemic injection of siRNA-packaged OMVs caused targeted gene silencing and induced highly significant tumor growth regression in an animal model. Importantly, the modified OMVs were well tolerated and showed no evidence of nonspecific side effects. We propose that bioengineered OMVs have great potential as cell-specific drug-delivery vehicles for treating various cancers.

Angiopoietin-1 (Ang1) has potential therapeutic applications in inducing angiogenesis, enhancing endothelial cell survival, and preventing vascular leakage. However, production of Ang1 is hindered by aggregation and insolubility resulting from disulfidelinked higher-order structures. Here, by replacing the N-terminal portion of Ang1 with the short coiled-coil domain of cartilage oligomeric matrix protein (COMP), we have generated a soluble, stable, and potent Ang1 variant, COMP-Ang1. This variant is more potent than native Ang1 in phosphorylating the tyrosine kinase with Ig and epidermal growth factor homology domain 2 (Tie2) receptor and Akt in primary cultured endothelial cells, enhancing angiogenesis in vitro and increasing adult angiogenesis in vivo. Thus, COMP-Ang1 is an effective alternative to native Ang1 for therapeutic angiogenesis in vivo.