A simple valuation model that allows for time variation in investment opportunities is developed and estimated. The model assumes that the investment opportunity set is completely described by two state variables, the real interest rate and the maximum Sharpe ratio, which follow correlated Ornstein-Uhlenbeck processes. The model parameters and time series of the state variables are estimated using data on US Treasury bond yields and inflation for the period January 1952 to December 2000. The estimated state variables are shown to be related to the equity premium and to the level of stock prices as measured by the dividend yield. Innovations in the estimated state variables are shown to be related to the returns on the Fama-French arbitrage portfolios, HML and SMB, providing a possible explanation for the risk premia on these portfolios. When tracking portfolios for the state variable innovations are constructed using returns on 6 size and book-to market equity sorted portfolios, the tracking portfolios explain the risk premia on HML and SMB, and these state variable tracking portfolios perform about as well as HML and SMB in explaining the cross-section of returns on the 25 size and book-to market equity sorted value weighted portfolios. An additional test of the ICAPM using returns on 30 industrial portfolios does not reject the model while the CAPM and the Fama-French 3 factor model are rejected using the same data.

SUMMARY Mdn1 is an essential AAA (ATPase Associated with various Activities) protein that removes assembly factors from distinct precursors of the ribosomal 60S subunit. However, Mdn1’s large size (~5000aa) and its limited homology to other well-studied proteins have restricted our understanding of its remodeling functions. Here, we present structures for S. pombe Mdn1 in the presence of AMPPNP at up to ~4Å, or ATP plus Rbin-1, a chemical inhibitor, at ~8Å. These data reveal that Mdn1’s MIDAS domain is tethered to its ring-shaped AAA domain through an ~20nm long structured linker and a flexible ~500aa Asp/Glu-rich motif. We find that the MIDAS domain, which also binds other ribosome-assembly factors, docks onto the AAA ring in a nucleotide state-specific manner. Together, our findings reveal how conformational changes in the AAA ring can be directly transmitted to the MIDAS domain and thereby drive the targeted release of assembly factors from ribosomal 60S-subunit precursors.

Bacteria use a process called quorum sensing to communicate and orchestrate collective behaviors including virulence factor secretion and biofilm formation. Quorum sensing relies on production, release, accumulation, and population-wide detection of signal molecules called autoinducers. Here, we develop concepts to coat surfaces with quorum-sensing-manipulation molecules as a method to control collective behaviors. We probe this strategy using Staphylococcus aureus. Pro- and anti-quorum-sensing molecules can be covalently attached to surfaces using click chemistry, where they retain their abilities to influence bacterial behaviors. We investigate key features of the compounds, linkers, and surfaces necessary to appropriately position molecules to interact with cognate receptors, and the ability of modified surfaces to resist long-term storage, repeated infections, host plasma components, and flow-generated stresses. Our studies highlight how this surface approach can be used to make colonization-resistant materials against S. aureus and other pathogens and how the approach can be adapted to promote beneficial behaviors of bacteria on surfaces.

G-quadruplex (G4) is a noncanonical secondary structure of DNA or RNA which can enhance or repress gene expression, yet the underlying molecular mechanism remains uncertain. Here we show that when positioned downstream of transcription start site, the orientation of potential G4 forming sequence (PQS), but not the sequence alters transcriptional output. Ensemble in vitro transcription assays indicate that PQS in the non-template increases mRNA production rate and yield. Using sequential single molecule detection stages, we demonstrate that while binding and initiation of T7 RNA polymerase is unchanged, the efficiency of elongation and the final mRNA output is higher when PQS is in the non-template. Strikingly, the enhanced elongation arises from the transcription-induced R-loop formation, which in turn generates G4 structure in the non-template. The G4 stabilized R-loop leads to increased transcription by a mechanism involving successive rounds of R-loop formation.