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A TAle of Two Pathways: Tail-Anchored Protein Insertion at the Endoplasmic Reticulum
No full textTail-anchored (TA) proteins are an essential class of integral membrane proteins required for many aspects of cellular physiology. TA proteins contain a single carboxy-terminal transmembrane domain that must be post-translationally recognized, guided to, and ultimately inserted into the correct cellular compartment. The majority of TA proteins begin their biogenesis in the endoplasmic reticulum (ER) and utilize two parallel strategies for targeting and insertion: the guided-entry of tail-anchored proteins (GET) and ER-membrane protein complex (EMC) pathways. Here we focus on how these two sets of machinery target, transfer, and insert TAs into the lipid bilayer in close collaboration with quality control machinery. Additionally, we highlight the unifying features of the insertion process as revealed by recent structures of the GET and EMC membrane protein complexes
The extent of intergalactic metal enrichment from galactic winds during the Cosmic Dawn
No full textOne of the key processes driving galaxy evolution during the Cosmic Dawn is supernova feedback. This likely helps regulate star formation inside of galaxies, but it can also drive winds that influence the large-scale intergalactic medium. Here, we present a simple semi-analytic model of supernova-driven galactic winds and explore the contributions of different phases of galaxy evolution to cosmic metal enrichment in the high-redshift (z ≳ 6) Universe. We show that models calibrated to the observed galaxy luminosity function at z ∼ 6–8 have filling factors ∼1% at z ∼ 6 and ∼0.1% at z ∼ 12, with different star formation prescriptions providing about an order of magnitude uncertainty. Despite the small fraction of space filled by winds, these scenarios predict an upper limit to the abundance of metal-line absorbers in quasar spectra at z ≳ 5 which is comfortably above that currently observed. We also consider enrichment through winds driven by Pop III star formation in minihalos. We find that these can dominate the total filling factor at z ≳ 10 and even compete with winds from normal galaxies at z ∼ 6, at least in terms of the total enriched volume. But these regions have much lower overall metallicities, because each one is generated by a small burst of star formation. Finally, we show that Compton cooling of these supernova-driven winds at z ≳ 6 has only a small effect on the cosmic microwave background
A 28-GHz, Multi-Beam, Decentralized Relay Array
No full textMulti-beam relays can be used to overcome the non-line-of-sight (NLOS) issues in millimeter-wave (mm-wave) communication networks that serve many users in an obstruction-rich environment. We demonstrate a modular multi-beam relay array at 28 GHz, which is scalable and fully decentralized. The individual branches of the array are independent and do not need to share a timing reference or be physically located on the same substrate. Multi-beam capability is facilitated by a multi-channel baseband signal conditioning chain that includes a reconfigurable, passive, inductorless, 3rd-order N-path filter with programmable frequency-independent phase shift. This baseband signal conditioning chain enables beams concurrently multiplexed in spatial and frequency domains. We present the theory, design, and operation of the custom RFIC, which enables independent multi-beam relaying. Multiple RFICs are used to create relay arrays. A four-element relay array demonstrates three independently steered beams that utilize the full array aperture with a total wireless throughput of 625 Mb/s
A puffy polar planet. The low density, hot Jupiter TOI-640 b is on a polar orbit
No full textTOI-640 b is a hot, puffy Jupiter with a mass of 0.57 ± 0.02 MJ and radius of 1.72 ± 0.05 RJ, orbiting a slightly evolved F-type star with a separation of 6.33_(−0.06)^(+0.07) R⋆. Through spectroscopic in-transit observations made with the HARPS spectrograph, we measured the Rossiter-McLaughlin effect, analysing both in-transit radial velocities and the distortion of the stellar spectral lines. From these observations, we find the host star to have a projected obliquity of λ = 184 ± 3°. From the TESS light curve, we measured the stellar rotation period, allowing us to determine the stellar inclination, i⋆ = 23_(−2)^(+3°), meaning we are viewing the star pole-on. Combining this with the orbital inclination allowed us to calculate the host star obliquity, ψ = 104 ± 2°. TOI-640 b joins a group of planets orbiting over stellar poles within the range 80°–125°. The origin of this orbital configuration is not well understood
Ultrafast Excited State Aromatization in Dihydroazulene
No full textExcited-state aromatization dynamics in the photochemical ring opening of dihydroazulene (DHA) is investigated by nonadiabatic molecular dynamics simulations in connection with the mixed-reference spin-flip (MRSF)-TDDFT method. It is found that, in the main reaction channel, the ring opening occurs in the excited state in a sequence of steps with increasing aromaticity. The first stage lasting ca. 200 fs produces an 8π semiaromatic S1 minimum (S_(1, min)) through an ultrafast damped bond length alternation (BLA) movement synchronized with a partial planarization of the cycloheptatriene ring. An additional ca. 200 fs are required to gain the vibrational energy needed to overcome a ring-opening transition state characterized by an enhanced Baird aromaticity. Unlike other BLA motions of ππ* state, it was shown that their damping is a characteristic feature of aromatic bond-equalization process. In addition, some minor channels of the reaction have also been discovered, where noticeably higher barriers of the S1non/antiaromatic transition structures must be surmounted. These anti-Baird channels led to reformation of DHA or other closed-ring products. The observed competition between the Baird and anti-Baird channels suggests that the quantum yield of photochemical products can be controllable by tipping their balance. Hence, here we suggest including the concept of anti-Baird, which would expand the applicability of Baird rule to much broader situations
Bias Correction and Statistical Modeling of Variable Oceanic Forcing of Greenland Outlet Glaciers
No full textVariability in oceanic conditions directly impacts ice loss from marine outlet glaciers in Greenland, influencing the ice sheet mass balance. Oceanic conditions are available from Atmosphere-Ocean Global Climate Model (AOGCM) output, but these models require extensive computational resources and lack the fine resolution needed to simulate ocean dynamics on the Greenland continental shelf and close to glacier marine termini. Here, we develop a statistical approach to generate ocean forcing for ice sheet model simulations, which incorporates natural spatiotemporal variability and anthropogenic changes. Starting from raw AOGCM ocean heat content, we apply: (a) a bias-correction using ocean reanalysis, (b) an extrapolation accounting for on-shelf ocean dynamics, and (c) stochastic time series models to generate realizations of natural variability. The bias-correction reduces model errors by ∼25% when compared to independent in-situ measurements. The bias-corrected time series are subsequently extrapolated to fjord mouth locations using relations constrained from available high-resolution regional ocean model results. The stochastic time series models reproduce the spatial correlation, characteristic timescales, and the amplitude of natural variability of bias-corrected AOGCMs, but at negligible computational expense. We demonstrate the efficiency of this method by generating >6,000 time series of ocean forcing for >200 Greenland marine-terminating glacier locations until 2100. As our method is computationally efficient and adaptable to any ocean model output and reanalysis product, it provides flexibility in exploring sensitivity to ocean conditions in Greenland ice sheet model simulations. We provide the output and workflow in an open-source repository, and discuss advantages and future developments for our method
Temporally resolved transcriptional recording in E. coli DNA using a Retro-Cascorder
No full textBiological signals occur over time in living cells. Yet most current approaches to interrogate biology, particularly gene expression, use destructive techniques that quantify signals only at a single point in time. A recent technological advance, termed the Retro-Cascorder, overcomes this limitation by molecularly logging a record of gene expression events in a temporally organized genomic ledger. The Retro-Cascorder works by converting a transcriptional event into a DNA barcode using a retron reverse transcriptase and then storing that event in a unidirectionally expanding clustered regularly interspaced short palindromic repeats (CRISPR) array via acquisition by CRISPR–Cas integrases. This CRISPR array-based ledger of gene expression can be retrieved at a later point in time by sequencing. Here we describe an implementation of the Retro-Cascorder in which the relative timing of transcriptional events from multiple promoters of interest is recorded chronologically in Escherichia coli populations over multiple days. We detail the molecular components required for this technology, provide a step-by-step guide to generate the recording and retrieve the data by Illumina sequencing, and give instructions for how to use custom software to infer the relative transcriptional timing from the sequencing data. The example recording is generated in 2 d, preparation of sequencing libraries and sequencing can be accomplished in 2–3 d, and analysis of data takes up to several hours. This protocol can be implemented by someone familiar with basic bacterial culture, molecular biology and bioinformatics. Analysis can be minimally run on a personal computer
Incorporating Full Elastodynamic Effects and Dipping Fault Geometries in Community Code Verification Exercises for Simulations of Earthquake Sequences and Aseismic Slip (SEAS)
No full textNumerical modeling of earthquake dynamics and derived insight for seismic hazard relies on credible, reproducible model results. The sequences of earthquakes and aseismic slip (SEAS) initiative has set out to facilitate community code comparisons, and verify and advance the next generation of physics-based earthquake models that reproduce all phases of the seismic cycle. With the goal of advancing SEAS models to robustly incorporate physical and geometrical complexities, here we present code comparison results from two new benchmark problems: BP1-FD considers full elastodynamic effects, and BP3-QD considers dipping fault geometries. Seven and eight modeling groups participated in BP1-FD and BP3-QD, respectively, allowing us to explore these physical ingredients across multiple codes and better understand associated numerical considerations. With new comparison metrics, we find that numerical resolution and computational domain size are critical parameters to obtain matching results. Codes for BP1-FD implement different criteria for switching between quasi-static and dynamic solvers, which require tuning to obtain matching results. In BP3-QD, proper remote boundary conditions consistent with specified rigid body translation are required to obtain matching surface displacements. With these numerical and mathematical issues resolved, we obtain excellent quantitative agreements among codes in earthquake interevent times, event moments, and coseismic slip, with reasonable agreements made in peak slip rates and rupture arrival time. We find that including full inertial effects generates events with larger slip rates and rupture speeds compared to the quasi-dynamic counterpart. For BP3-QD, both dip angle and sense of motion (thrust versus normal faulting) alter ground motion on the hanging and foot walls, and influence event patterns, with some sequences exhibiting similar-size characteristic earthquakes, and others exhibiting different-size events. These findings underscore the importance of considering full elastodynamics and nonvertical dip angles in SEAS models, as both influence short- and long-term earthquake behavior and are relevant to seismic hazard
Exponentially Convergent Multiscale Finite Element Method
No full textWe provide a concise review of the exponentially convergent multiscale finite element method (ExpMsFEM) for efficient model reduction of PDEs in heterogeneous media without scale separation and in high-frequency wave propagation. The ExpMsFEM is built on the non-overlapped domain decomposition in the classical MsFEM while enriching the approximation space systematically to achieve a nearly exponential convergence rate regarding the number of basis functions. Unlike most generalizations of the MsFEM in the literature, the ExpMsFEM does not rely on any partition of unity functions. In general, it is necessary to use function representations dependent on the right-hand side to break the algebraic Kolmogorov n-width barrier to achieve exponential convergence. Indeed, there are online and offline parts in the function representation provided by the ExpMsFEM. The online part depends on the right-hand side locally and can be computed in parallel efficiently. The offline part contains basis functions that are used in the Galerkin method to assemble the stiffness matrix; they are all independent of the right-hand side, so the stiffness matrix can be used repeatedly in multi-query scenarios
Multi-stage Stern–Gerlach experiment modeled
No full textIn the classic multi-stage Stern–Gerlach experiment conducted by Frisch and Segrè, the Majorana (Landau–Zener) and Rabi formulae diverge far from the experimental observation while the physical mechanism for electron-spin collapse remains unidentified. Here, introducing the physical co-quantum concept provides a plausible physical mechanism and predicts the experimental observation in absolute units without fitting (i.e. no parameters adjusted), with a p-value less than one per million, which is the probability that the co-quantum theory happens to match the experimental observation purely by chance. Further, the co-quantum concept is corroborated by exactly statistically reproducing the wave function, density operator, and uncertainty relation for electron spin in Stern–Gerlach experiments