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The spliceosome undergoes extensive rearrangements as it assembles onto precursor messenger RNAs. In the earliest assembly step, U1snRNA identifies the 5′ splice site. However, U1snRNA leaves the spliceosome relatively early in assembly, and 5′ splice site identity is subsequently maintained through interactions with U6snRNA, protein factor PRP8, and other components during the rearrangements that build the catalytic site. Using a forward genetic screen in Caenorhabditis elegans, we have identified suppressors of a locomotion defect caused by a 5′ss mutation. Here we report three new suppressor alleles from this screen, two in PRP8 and one in SNRNP200/BRR2. mRNASeq studies of these suppressor strains indicate that they also affect specific native alternative 5′ss, especially for suppressor PRP8 D1549N. A strong suppressor at the unstructured N-terminus of SNRNP200, N18K, indicates a novel role for this region. By examining distinct changes in the splicing of native genes, examining double mutants between suppressors, comparing these new suppressors to previously identified splicing suppressors from yeast, and mapping conserved suppressor residues onto cryoEM structural models of assembling human spliceosomes, we conclude that there are multiple interactions at multiple stages in spliceosome assembly responsible for maintaining the initial 5′ss identified by U1snRNA for entry into the catalyticmore »core.

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The Great Oxidation Event was a period during which Earth’s atmospheric oxygen (O2) concentrations increased from ∼10−5 times its present atmospheric level (PAL) to near modern levels, marking the start of the Proterozoic geological eon 2.4 billion years ago. Using WACCM6, an Earth System Model, we simulate the atmosphere of Earth-analogue exoplanets with O2 mixing ratios between 0.1 and 150 per cent PAL. Using these simulations, we calculate the reflection spectra over multiple orbits using the Planetary Spectrum Generator. We highlight how observer angle, albedo, chemistry, and clouds affect the simulated observations. We show that inter-annual climate variations, as well short-term variations due to clouds, can be observed in our simulated atmospheres with a telescope concept such as LUVOIR or HabEx. Annual variability and seasonal variability can change the planet’s reflected flux (including the reflected flux of key spectral features such as O2 and H2O) by up to factors of 5 and 20, respectively, for the same orbital phase. This variability is best observed with a high-throughput coronagraph. For example, HabEx (4 m) with a starshade performs up to a factor of two times better than a LUVOIR B (6 m) style telescope. The variability and signal-to-noise ratio of some spectral features dependsmore »non-linearly on atmospheric O2 concentration. This is caused by temperature and chemical column depth variations, as well as generally increased liquid and ice cloud content for atmospheres with O2 concentrations of <1 per cent PAL.

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We have observed a significant enhancement in the energy deposition by 25–$$100~\textrm{GeV}$$$100\text{GeV}$photons in a$$1~\textrm{cm}$$$1\text{cm}$thick tungsten crystal oriented along its$$\langle 111 \rangle $$$⟨111⟩$lattice axes. At$$100~\textrm{GeV}$$$100\text{GeV}$, this enhancement, with respect to the value observed without axial alignment, is more than twofold. This effect, together with the measured huge increase in secondary particle generation is ascribed to the acceleration of the electromagnetic shower development by the strong axial electric field. The experimental results have been critically compared with a newly developed Monte Carlo adapted for use with crystals of multi-$$X_0$$$X_0$thickness. The results presented in this paper may prove to be of significant interest for the development of high-performance photon absorbers and highly compact electromagnetic calorimeters and beam dumps for use at the energy and intensity frontiers.

The Casimir effect in graphene systems is reviewed with a emphasis made on the large thermal correction to the Casimir force predicted at short separations between the test bodies. The computational results for the Casimir pressure and for the thermal correction are presented for both pristine graphene and real graphene sheets, which possess nonzero energy gap and chemical potential, obtained by means of exact polarization tensor. Two experiments on measuring the gradient of the Casimir force between an Au-coated sphere and graphene-coated substrates performed by using a modified atomic force microscope cantilever-based technique are described. It is shown that the measurement data of both experiments are in agreement with theoretical predictions of the Lifshitz theory using the polarization tensor. Additionally, several important improvements made in the second experiment, allowed to demonstrate the predicted large thermal effect in the Casimir interaction at short separations. Possible implications of this result to the resolution of long-term problems of Casimir physics are discussed.

The development of new modes at x-ray free electron lasers has inspired novel methods for studying fluctuations at different energies and timescales. For closely spaced x-ray pulses that can be varied on ultrafast time scales, we have constructed a pair of advanced instruments to conduct studies targeting quantum materials. We first describe a prototype instrument built to test the proof-of-principle of resonant magnetic scattering using ultrafast pulse pairs. This is followed by a description of a new endstation, the so-called fluctuation–dissipation measurement instrument, which was used to carry out studies with a fast area detector. In addition, we describe various types of diagnostics for single-shot contrast measurements, which can be used to normalize data on a pulse-by-pulse basis and calibrate pulse amplitude ratios, both of which are important for the study of fluctuations in materials. Furthermore, we present some new results using the instrument that demonstrates access to higher momentum resolution.

Subduction zones represent the interface between Earth’s interior (crust and mantle) and exterior (atmosphere and oceans), where carbon and other volatile elements are actively cycled between Earth reservoirs by plate tectonics. Helium is a sensitive tracer of volatile sources and can be used to deconvolute mantle and crustal sources in arcs; however it is not thought to be recycled into the mantle by subduction processes. In contrast, carbon is readily recycled, mostly in the form of carbon-rich sediments, and can thus be used to understand volatile delivery via subduction. Further, carbon is chemically-reactive and isotope fractionation can be used to determine the main processes controlling volatile movements within arc systems. Here, we report helium isotope and abundance data for 42 deeply-sourced fluid and gas samples from the Central Volcanic Zone (CVZ) and Southern Volcanic Zone (SVZ) of the Andean Convergent Margin (ACM). Data are used to assess the influence of subduction parameters (e.g., crustal thickness, subduction inputs, and convergence rate) on the composition of volatiles in surface volcanic fluid and gas emissions. He isotopes from the CVZ backarc range from 0.1 to 2.6 R A ( n = 23), with the highest values in the Puna and the lowest inmore »the Sub-Andean foreland fold-and-thrust belt. Atmosphere-corrected He isotopes from the SVZ range from 0.7 to 5.0 R A ( n = 19). Taken together, these data reveal a clear southeastward increase in 3 He/ 4 He, with the highest values (in the SVZ) falling below the nominal range associated with pure upper mantle helium (8 ± 1 R A ), approaching the mean He isotope value for arc gases of (5.4 ± 1.9 R A ). Notably, the lowest values are found in the CVZ, suggesting more significant crustal inputs (i.e., assimilation of 4 He) to the helium budget. The crustal thickness in the CVZ (up to 70 km) is significantly larger than in the SVZ, where it is just ∼40 km. We suggest that crustal thickness exerts a primary control on the extent of fluid-crust interaction, as helium and other volatiles rise through the upper plate in the ACM. We also report carbon isotopes from ( n = 11) sites in the CVZ, where δ 13 C varies between −15.3‰ and −1.2‰ [vs. Vienna Pee Dee Belemnite (VPDB)] and CO 2 / 3 He values that vary by over two orders of magnitude (6.9 × 10 8 –1.7 × 10 11 ). In the SVZ, carbon isotope ratios are also reported from ( n = 13) sites and vary between −17.2‰ and −4.1‰. CO 2 / 3 He values vary by over four orders of magnitude (4.7 × 10 7 –1.7 × 10 12 ). Low δ 13 C and CO 2 / 3 He values are consistent with CO 2 removal (e.g., calcite precipitation and gas dissolution) in shallow hydrothermal systems. Carbon isotope fractionation modeling suggests that calcite precipitation occurs at temperatures coincident with the upper temperature limit for life (122°C), suggesting that biology may play a role in C-He systematics of arc-related volcanic fluid and gas emissions.« less

In mechanics, the standard 3-credit, 45-hour course is sufficient to deliver standard lectures with prepared examples and questions. Moreover, it is not only feasible, but preferable, to employ any of a variety of active learning and teaching techniques. Nevertheless, even when active learning is strategically used, students and instructors alike experience pressure to accomplish their respective learning and teaching goals under the constraints of the academic calendar, raising questions as to whether the allocated time is sufficient to enable authentic learning. One way to assess learning progress is to examine the learning cycles through which students attempt, re-think, and re-attempt their work. This article provides data to benchmark the time required to learn key Statics concepts based on results of instruction of approximately 50 students in a Statics class at a public research university during the Fall 2020 semester. Two parallel techniques are employed to foster and understand student learning cycles. • Through a Mastery Based Learning model, 15 weekly pass/fail “Mastery Tests” are given. Students who do not pass may re-test with a different but similar test on the same topic each week until the semester’s conclusion. The tests are highly structured in that they are well posed andmore »highly focused. For example, some tests focus only on drawing Free Body Diagrams, with no equations or calculations. Other tests focus on writing equilibrium equations from a given Free Body Diagram. Passing the first six tests is required to earn the grade of D; passing the next three for C; the next three for B; and the final three for A. Evaluations include coding of student responses to infer student reasoning. Learning cycles occur as students repeat the same topics, and their progress is assessed by passing rates and by comparing evolving responses to the same test topics. • Concept Questions that elicit qualitative responses and written explanations are deployed at least weekly. The learning cycle here consists of students answering a question, seeing the overall class results (but without the correct answer), having a chance to explore the question with other students and the instructor, and finally an opportunity to re-answer the same question, perhaps a few minutes or up to a couple days later. Sometimes, that same question is given a third time to encourage further effort or progress. To date, results from both cycles appear to agree on one important conclusion: the rate of demonstrated learning is quite low. For example, each Mastery Test has a passing rate of 20%-30%, including for students with several repeats. With the Concept Questions, typically no more than half of the students who answered incorrectly change to the correct answer by the time of the final poll. The final article will provide quantitative and qualitative results from each type of cycle, including tracking coded responses on Mastery Tests, written responses on Concept Questions, and cross-comparisons thereof. Additional results will be presented from student surveys. Since the Mastery Tests and Concept Questions follow typical Statics topics, this work has potential to lead to a standardized set of benchmarks and standards for measuring student learning – and its rate – in Statics.« less