The use of magnetic nanorobots to activate chemotherapeutic prodrugs represents a promising alternative to current chemotherapeutic treatments. Here, a hybrid nanowire (NW) for targeted bioorthogonally driven activation of the latent chemotherapeutic prodrug 5‐fluoro‐1‐propargyl‐uracil (Pro‐5‐FU) in in vitro and in vivo cancer models is proposed. The NWs are composed of magnetic iron (Fe) and palladium (Pd), a known bioorthogonal catalyst. In vitro tests with a cancer cell line showed no significant cytotoxic effect by the NWs. In contrast, NWs combined with Pro‐5‐FU lead to a significant reduction of cell viability, similarly to the one induced by its active chemotherapeutic counterpart 5‐fluorouracil (5‐FU). The reduction in cell viability is attributed to the catalytic activation of Pro‐5‐FU into 5‐FU. To demonstrate their targeted therapeutic abilities, magnetic fields are used to attract the FePd NWs to a predefined area within a cultured cancer cell population, causing a local Pro‐5‐FU activation, and subsequent cell death in this region. As a proof of concept, NWs are injected in cancer tumor xenografts. The intraperitoneal injection of Pro‐5‐FU significantly retards tumour growth without causing significant side effects. This work presents a novel chemotherapeutic approach combining nanorobotics and bioorthogonal activation of prodrugs as an efficient alternative to conventional chemotherapy.

This paper shows that the revised loan loss provisioning based on the International Financial Reporting Standards (IFRS) and the Generally Accepted Accounting Principles (GAAP) implies a reduction of Tier 1 capital which levies an additional burden on banks.The paper finds in a counterfactual analysis that these changes are more severe (i) during economic downturns, (ii) for credit portfolios of low quality, (iii) for banks that do not tighten capital standards during downturns, and (iv) under a more lenient definition of significant increase in credit risk (SICR) under IFRS. Hence, the provisioning rules further increase the procyclicality of bank capital requirements. Adjustments of the SICR threshold or capital buffers are suggested as ways to mitigate a regulatory pressure that may emerges due to the reduction of regulatory capital.JEL classification: C51, G28, M48

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The New Basel Capital Accord will allow the determination of banks' regulatory capital requirements due to probabilities of default which are estimated and forecasted from internal ratings. Broadly, two rating philosophies are distinguished: Through the Cycle versus Point in Time Ratings. We employ a Likelihood-Ratio backtesting of both types with respect to their probability of default forecasts and correlations derived from a nonlinear random effects panel model using data from Standard & Poor's. The implications for risk capital using these different philosophies are demonstrated. It is shown that Point in Time Ratings will exhibit much lower correlations and, thus, default probability forecasts should be more precise. As a consequence, Value at Risk quantiles of default distributions should be lower than those generated by Through the Cycle Ratings. Nevertheless banks which use Point in Time Ratings may be punished in times of economic stress if the implied reduction of asset correlation is not taken into account.

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This paper provides evidence for the relationship between credit quality, recovery rate, and correlation. The paper finds that rating grade, rating shift, and macroeconomic factors provide a highly significant explanation for default risk and recovery risk of US bond issues. The empirical data suggest that default and recovery processes are highly correlated. Therefore, a joint approach is required for estimating time-varying default probabilities and recovery rates that are conditional on default. This paper develops and applies such a model.