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[Ru(bipy)₃]⁺is a key intermediate in the chemistry of the ubiquitous [Ru(bipy)₃]²⁺, including in recent photoredox applications. Isolation helps to illuminate the monocation’s structure and potential roles in catalytic reactivity.

 

Training for robotic surgery can be challenging due the complexity of the technology, as well as a high demand for the robotic systems that must be primarily used for clinical care. While robotic surgical skills are traditionally trained using the robotic hardware coupled with physical simulated tissue models and test-beds, there has been an increasing interest in using virtual reality simulators. Use of virtual reality (VR) comes with some advantages, such as the ability to record and track metrics associated with learning. However, evidence of skill transfer from virtual environments to physical robotic tasks has yet to be fully demonstrated. In this work, we evaluate the effect of virtual reality pre-training on performance during a standardized robotic dry-lab training curriculum, where trainees perform a set of tasks and are evaluated with a score based on completion time and errors made during the task. Results show that VR pre-training is weakly significant ([Formula: see text]) in reducing the number of repetitions required to achieve proficiency on the robotic task; however, it is not able to significantly improve performance in any robotic tasks. This suggests that important skills are learned during physical training with the surgical robotic system that cannot yet be replaced with VR training. 

Mass movements from glacial and lahar terraces in the middle and lower reaches of rivers draining the Washington Cascade Range to Puget Sound may represent a substantial but poorly quantified portion of those rivers' sediment supply and pose significant mass movement hazards. We used repeat LiDAR elevation data, aerial imagery, and well logs to quantify and characterize terrace sediment delivery in nine major watersheds over a median period of 12 years. In the 1,946 river kilometers for which repeat LiDAR was available (71% of the 2,736 total river kilometers flanked by terraces), 167 mass movements eroded 853,600 ± 19,400 m³/yr. Analysis of mass movement frequency and volume indicates that terrace sediment delivery is dominated by small, frequent mass movements, as opposed to large, infrequent ones like the 2014 Oso landslide. This sediment source is low in river networks, well connected to streams, and has a substantial coarse‐grained and durable component, all of which increase its significance to sedimentation in developed, lowland reaches. However, rates of terrace sediment delivery vary among basins and between adjacent terraces, which are stratigraphically laterally heterogeneous. While lateral fluvial erosion is usually necessary to initiate terrace mass movements, valley bottom geometry and terrace stratigraphy poorly predict erosion volume, which is better predicted by hillslope geometry and mass movement style. Effective management of sedimentation and mass movement hazard should acknowledge the importance of terrace sediment delivery and the variability among and within watersheds in sediment delivery, sediment characteristics, and failure mechanisms.

 

The trend for improved more precise diagnostics and management of disease heavily relies on the measurement of panels of biomarkers in physiological samples of patients. Ideally, the ultimate goal would be to detect as many clinically relevant biomarkers as possible in a single drop of blood, achieving quick, sensitive, reproducible, and affordable detection in small volume physiological samples. Bioluminescent (BL) proteins provide many of the desired characteristics required for such labels, including detection at extremely low concentrations, no interference from physiological fluids leading to excellent detection limits, and compatibility with many miniaturized systems. However, to date the use of BL proteins has been restricted by their limited multiplexing capabilities. BL proteins typically exhibit a single emission profile and decay kinetics making the simultaneous detection of multiple analytes difficult. Recent progresses in this area include the use of two different engineered luminescent proteins to achieve resolved signals via one-dimensional time resolution. This approach, however, to date only lead to a dual analyte detection. Herein, we have demonstrated that using a two-dimensional approach that combines both temporal and spatial resolution, we can expand the multiplexing capabilities of bioluminescent proteins. To that end, the photoprotein aequorin (AEQ) has been employed for the simultaneous detection of three separate analytes in a single well, differentiated through the use of three discrete time/wavelength windows. Through a combination of site-specific mutations and synthetic coelenterazines “semi-synthetic” AEQ variants have been developed with altered emission profiles and decay kinetics. In this study, two AEQ mutant proteins were genetically conjugated to three pro-inflammatory cytokines (tumor necrosis factor alpha, interleukins 6 and 8) resulting in AEQ-labeled cytokines. These fusion proteins were combined with synthetic coelenterazines resulting in proteins with differing emission maxima and half-lives to allow for the simultaneous detection of all three cytokines in a single sample. The validity of the assay was demonstrated in serum by employing human physiological samples and comparing our results with commercially available individual tests for each of the three cytokines. 

The small GTPase KRAS is localized at the plasma membrane where it functions as a molecular switch, coupling extracellular growth factor stimulation to intracellular signaling networks. In this process, KRAS recruits effectors, such as RAF kinase, to the plasma membrane where they are activated by a series of complex molecular steps. Defining the membrane-bound state of KRAS is fundamental to understanding the activation of RAF kinase and in evaluating novel therapeutic opportunities for the inhibition of oncogenic KRAS-mediated signaling. We combined multiple biophysical measurements and computational methodologies to generate a consensus model for authentically processed, membrane-anchored KRAS. In contrast to the two membrane-proximal conformations previously reported, we identify a third significantly populated state using a combination of neutron reflectivity, fast photochemical oxidation of proteins (FPOP), and NMR. In this highly populated state, which we refer to as “membrane-distal” and estimate to comprise ∼90% of the ensemble, the G-domain does not directly contact the membrane but is tethered via its C-terminal hypervariable region and carboxymethylated farnesyl moiety, as shown by FPOP. Subsequent interaction of the RAF1 RAS binding domain with KRAS does not significantly change G-domain configurations on the membrane but affects their relative populations. Overall, our results are consistent with a directional fly-casting mechanism for KRAS, in which the membrane-distal state of the G-domain can effectively recruit RAF kinase from the cytoplasm for activation at the membrane.