Computationally designed sensors detect endogenous Ras activity and signaling effectors at subcellular resolution.

The utility of genetically encoded biosensors for sensing the activity of signaling proteins has been hampered by a lack of strategies for matching sensor sensitivity to the physiological concentration range of the target. Here we used computational protein design to generate intracellular sensors of Ras activity (LOCKR-based Sensor for Ras activity (Ras-LOCKR-S)) and proximity labelers of the Ras signaling environment (LOCKR-based, Ras activity-dependent Proximity Labeler (Ras-LOCKR-PL)). These tools allow the detection of endogenous Ras activity and labeling of the surrounding environment at subcellular resolution. Using these sensors in human cancer cell lines, we identified Ras-interacting proteins in oncogenic EML4-Alk granules and found that Src-Associated in Mitosis 68-kDa (SAM68) protein specifically enhances Ras activity in the granules. The ability to subcellularly localize endogenous Ras activity should deepen our understanding of Ras function in health and disease and may suggest potential therapeutic strategies.

Cesium Lead Halide Perovskites with Improved Stability for Tandem Solar Cells.

A semiconductor that can be processed on a large scale with a bandgap around 1.8 eV could enable the manufacture of highly efficient low cost double-junction solar cells on crystalline Si. Solution-processable organic-inorganic halide perovskites have recently generated considerable excitement as absorbers in single-junction solar cells, and though it is possible to tune the bandgap of (CH3NH3)Pb(BrxI1-x)3 between 2.3 and 1.6 eV by controlling the halide concentration, optical instability due to photoinduced phase segregation limits the voltage that can be extracted from compositions with appropriate bandgaps for tandem applications. Moreover, these materials have been shown to suffer from thermal degradation at temperatures within the processing and operational window. By replacing the volatile methylammonium cation with cesium, it is possible to synthesize a mixed halide absorber material with improved optical and thermal stability, a stabilized photoconversion efficiency of 6.5%, and a bandgap of 1.9 eV.

Enhancing the hole-conductivity of spiro-OMeTAD without oxygen or lithium salts by using spiro(TFSI)2 in perovskite and dye-sensitized solar cells.

2,2',7,7'-Tetrakis(N,N-di-p-methoxyphenylamine)-9,9'-spirobifluorene (spiro-OMeTAD), the prevalent organic hole transport material used in solid-state dye-sensitized solar cells and perovskite-absorber solar cells, relies on an uncontrolled oxidative process to reach appreciable conductivity. This work presents the use of a dicationic salt of spiro-OMeTAD, named spiro(TFSI)2, as a facile means of controllably increasing the conductivity of spiro-OMeTAD up to 10(-3) S cm(-1) without relying on oxidation in air. Spiro(TFSI)2 enables the first demonstration of solid-state dye-sensitized solar cells fabricated and operated with the complete exclusion of oxygen after deposition of the sensitizer with higher and more reproducible device performance. Perovskite-absorber solar cells fabricated with spiro(TFSI)2 show improved operating stability in an inert atmosphere. Gaining control of the conductivity of the HTM in both dye-sensitized and perovskite-absorber solar cells in an inert atmosphere using spiro(TFSI)2 is an important step toward the commercialization of these technologies.

The importance of dye chemistry and TiCl4 surface treatment in the behavior of Al2O3 recombination barrier layers deposited by atomic layer deposition in solid-state dye-sensitized solar cells.

Atomic layer deposition (ALD) was used to fabricate Al(2)O(3) recombination barriers in solid-state dye-sensitized solar cells (ss-DSSCs) employing an organic hole transport material (HTM) for the first time. Al(2)O(3) recombination barriers of varying thickness were incorporated into efficient ss-DSSCs utilizing the Z907 dye adsorbed onto a 2 µm-thick nanoporous TiO(2) active layer and the HTM spiro-OMeTAD. The impact of Al(2)O(3) barriers was also studied in devices employing different dyes, with increased active layer thicknesses, and with substrates that did not undergo the TiCl(4) surface treatment. In all instances, electron lifetimes (as determined by transient photovoltage measurements) increased and dark current was suppressed after Al(2)O(3) deposition. However, only when the TiCl(4) treatment was eliminated did device efficiency increase; in all other instances efficiency decreased due to a drop in short-circuit current. These results are attributed in the former case to the similar effects of Al(2)O(3) ALD and the TiCl(4) surface treatment whereas the insulating properties of Al(2)O(3) hinder charge injection and lead to current loss in TiCl(4)-treated devices. The impact of Al(2)O(3) barrier layers was unaffected by doubling the active layer thickness or using an alternative ruthenium dye, but a metal-free donor-π-acceptor dye exhibited a much smaller decrease in current due to its higher excited state energy. We develop a model employing prior research on Al(2)O(3) growth and dye kinetics that successfully predicts the reduction in device current as a function of ALD cycles and is extendable to different dye-barrier systems.

Selective heteronuclear Hartmann-Hahn: a multiple-pulse sequence for selective magnetization transfer in the structural elucidation of "isotagged" oligosaccharides.

A new selective heteronuclear Hartmann-Hahn (SHEHAHA) multiple-pulse mixing sequence is proposed for the solution structure elucidation of milligram amounts of peracetylated oligosaccharides in which the acetyl groups are enriched in carbon-13, so-called "isotags". SHEHAHA accomplishes exclusive in-phase magnetization transfer between the isotag carbonyl (13)C and the proximal proton on the sugar ring. Relayed transfer around the sugar rings by proton-proton TOCSY is suppressed, while the heteronuclear transfer from the labeled carbonyl carbon to the proximal ring proton is maintained. The sequence is broadband in the sense that all acetyl groups simultaneously give good signal transfer to their respective nearest proton neighbors. The (1)H-detected spectra have decent sensitivity and excellent resolution, giving patterns that unambiguously identify common structural subunits in human glycans. Peracetylated maltitol is shown as a test case of the method. Lineshapes are pure absorption, allowing facile measurement of vicinal proton-proton couplings. Linkage points can be deduced, and the 2D correlation spectra may be useful for more ambitious prediction algorithms and machine identification by a spectral database.