A single transcription factor is sufficient to induce and maintain secretory cell architecture

We hypothesized that basic helix–loop–helix (bHLH) MIST1 (BHLHA15) is a “scaling factor” that universally establishes secretory morphology in cells that perform regulated secretion. Here, we show that targeted deletion of MIST1 caused dismantling of the secretory apparatus of diverse exocrine cells. Parietal cells (PCs), whose function is to pump acid into the stomach, normally lack MIST1 and do not perform regulated secretion. Forced expression of MIST1 in PCs caused them to expand their apical cytoplasm, rearrange mitochondrial/lysosome trafficking, and generate large secretory granules. Mist1 induced a cohort of genes regulated by MIST1 in multiple organs but did not affect PC function. MIST1 bound CATATG/CAGCTG E boxes in the first intron of genes that regulate autophagosome/lysosomal degradation, mitochondrial trafficking, and amino acid metabolism. Similar alterations in cell architecture and gene expression were also caused by ectopically inducing MIST1 in vivo in hepatocytes. Thus, MIST1 is a scaling factor necessary and sufficient by itself to induce and maintain secretory cell architecture. Our results indicate that, whereas mature cell types in each organ may have unique developmental origins, cells performing similar physiological functions throughout the body share similar transcription factor-mediated architectural “blueprints.

Ionization and Ionization-Excitation of Helium to the n=1-4 States of He⁺ by Electron Impact

We present experimental and theoretical results for the electron-impact-induced ionization of ground-state helium atoms. Using a high-sensitivity toroidal electron spectrometer, we measured cross-section ratios for transitions leading to the first three excited states of the residual helium ion relative to the transition leaving the ion in the ground state. Measurements were performed for both symmetric- and asymmetric-energy-sharing kinematics. By presenting results as a ratio, a direct comparison can be made between theoretical and experimental predictions without recourse to normalization. The experimental data are compared to theoretical predictions employing various first-order models and a second-order hybrid distorted-wave + convergent R matrix with pseudostates (close-coupling) approach. All the first-order models fail in predicting even the approximate size of the cross-section ratios. The second-order calculations are found to describe the experimental data for asymmetric-energy-sharing with reasonable fidelity, although significant disparities are evident for the symmetric-energy-sharing cases. These comparisons demonstrate the need for further theoretical developments, in which all four charged particles are treated on an equal footing

Group trust dynamics during a risky driving experience in a Tesla Model X

The growing concern about the risk and safety of autonomous vehicles (AVs) has made it vital to understand driver trust and behavior when operating AVs. While research has uncovered human factors and design issues based on individual driver performance, there remains a lack of insight into how trust in automation evolves in groups of people who face risk and uncertainty while traveling in AVs. To this end, we conducted a naturalistic experiment with groups of participants who were encouraged to engage in conversation while riding a Tesla Model X on campus roads. Our methodology was uniquely suited to uncover these issues through naturalistic interaction by groups in the face of a risky driving context. Conversations were analyzed, revealing several themes pertaining to trust in automation: (1) collective risk perception, (2) experimenting with automation, (3) group sense-making, (4) human-automation interaction issues, and (5) benefits of automation. Our findings highlight the untested and experimental nature of AVs and confirm serious concerns about the safety and readiness of this technology for on-road use. The process of determining appropriate trust and reliance in AVs will therefore be essential for drivers and passengers to ensure the safe use of this experimental and continuously changing technology. Revealing insights into social group–vehicle interaction, our results speak to the potential dangers and ethical challenges with AVs as well as provide theoretical insights on group trust processes with advanced technology

Toward a more realistic representation of surface albedo in NASA CERES-derived surface radiative fluxes: A comparison with the MOSAiC field campaign

Accurate multidecadal radiative flux records are vital to understand Arctic amplification and constrain climate model uncertainties. Uncertainty in the NASA Clouds and the Earth&rsquo;s Radiant Energy System (CERES)-derived irradiances is larger over sea ice than any other surface type and comes from several sources. The year-long Multidisciplinary drifting Observatory for the Study of Arctic Climate (MOSAiC) expedition in the central Arctic provides a rare opportunity to explore uncertainty in CERES-derived radiative fluxes. First, a systematic and statistically robust assessment of surface shortwave and longwave fluxes was conducted using in situ measurements from MOSAiC flux stations. The CERES Synoptic 1degree (SYN1deg) product overestimates the downwelling shortwave flux by +11.40 Wm&ndash;2 and underestimates the upwelling shortwave flux by &ndash;15.70 Wm&ndash;2 and downwelling longwave fluxes by &ndash;12.58 Wm&ndash;2 at the surface during summer. In addition, large differences are found in the upwelling longwave flux when the surface approaches the melting point (approximately 0&deg;C). The biases in downwelling shortwave and longwave fluxes suggest that the atmosphere represented in CERES is too optically thin. The large negative bias in upwelling shortwave flux can be attributed in large part to lower surface albedo (&ndash;0.15) in satellite footprint relative to surface sensors. Additionally, the results show that the spectral surface albedo used in SYN1deg overestimates albedo in visible and mid-infrared bands. A series of radiative transfer model perturbation experiments are performed to quantify the factors contributing to the differences. The CERES-MOSAiC broadband albedo differences (approximately 20 Wm&ndash;2) explain a larger portion of the upwelling shortwave flux difference than the spectral albedo shape differences (approximately 3 Wm&ndash;2). In addition, the differences between perturbation experiments using hourly and monthly MOSAiC surface albedo suggest that approximately 25% of the sea ice surface albedo variability is explained by factors not correlated with daily sea ice concentration variability. Biases in net shortwave and longwave flux can be reduced to less than half by adjusting both albedo and cloud inputs toward observed values. The results indicate that improvements in the surface albedo and cloud data would substantially reduce the uncertainty in the Arctic surface radiation budget derived from CERES data products. &nbsp;</p

Hyperfine Spectroscopy of Isotopically Engineered Group-IV Color Centers in Diamond

A quantum register coupled to a spin-photon interface is a key component in quantum communication and information processing. Group-IV color centers in diamond (SiV, GeV, and SnV) are promising candidates for this application, comprising an electronic spin with optical transitions coupled to a nuclear spin as the quantum register. However, the creation of a quantum register for these color centers with deterministic and strong coupling to the spin-photon interface remains challenging. Here, we make first-principles predictions of the hyperfine parameters of the group-IV color centers, which we verify experimentally with a comprehensive comparison between the spectra of spin active and spin neutral intrinsic dopant nuclei in single GeV and SnV emitters. In line with the theoretical predictions, detailed spectroscopy on large sample sizes reveals that hyperfine coupling causes a splitting of the optical transition of SnV an order of magnitude larger than the optical linewidth and provides a magnetic-field insensitive transition. This strong coupling provides access to a new regime for quantum registers in diamond color centers, opening avenues for novel spin-photon entanglement and quantum sensing schemes for these well-studied emitters

Multi-Frequency Electrocochleography and Electrode Scan to Identify Electrode Insertion Trauma during Cochlear Implantation

Intraoperative electrocochleography (ECOG) is performed using a single low-frequency acoustic stimulus (e.g., 500 Hz) to monitor cochlear microphonics (CM) during cochlear implant (CI) electrode insertion. A decrease in CM amplitude is commonly associated with cochlear trauma and is used to guide electrode placement. However, advancement of the recording electrode beyond the sites of CM generation can also lead to a decrease in CM amplitude and is sometimes interpreted as cochlear trauma, resulting in unnecessary electrode manipulation and increased risk of cochlear trauma during CI electrode placement. In the present study, multi-frequency ECOG was used to monitor CM during CI electrode placement. The intraoperative CM tracings were compared with electrode scan measurements, where CM was measured for each of the intracochlear electrodes. Comparison between the peak CM amplitude measured during electrode placement and electrode scan measurements was used to differentiate between different mechanisms for decrease in CM amplitude during CI electrode insertion. Analysis of the data shows that both multi-frequency electrocochleography and electrode scan could potentially be used to differentiate between different mechanisms for decreasing CM amplitude and providing appropriate feedback to the surgeon during CI electrode placement

A warm Jet in a cold ocean

Unprecedented quantities of heat are entering the Pacific sector of the Arctic Ocean through Bering Strait, particularly during summer months. Though some heat is lost to the atmosphere during autumn cooling, a significant fraction of the incoming warm, salty water subducts (dives beneath) below a cooler fresher layer of near-surface water, subsequently extending hundreds of kilometers into the Beaufort Gyre. Upward turbulent mixing of these sub-surface pockets of heat is likely accelerating sea ice melt in the region. This Pacific-origin water brings both heat and unique biogeochemical properties, contributing to a changing Arctic ecosystem. However, our ability to understand or forecast the role of this incoming water mass has been hampered by lack of understanding of the physical processes controlling subduction and evolution of this this warm water. Crucially, the processes seen here occur at small horizontal scales not resolved by regional forecast models or climate simulations; new parameterizations must be developed that accurately represent the physics. Here we present novel high resolution observations showing the detailed process of subduction and initial evolution of warm Pacific-origin water in the southern Beaufort Gyre

Spontaneous vortices in the formation of Bose-Einstein condensates

Phase transitions are ubiquitous in nature, ranging from protein folding and denaturisation, to the superconductor-insulator quantum phase transition, to the decoupling of forces in the early universe. Remarkably, phase transitions can be arranged into universality classes, where systems having unrelated microscopic physics exhibit identical scaling behaviour near the critical point. Here we present an experimental and theoretical study of the Bose-Einstein condensation phase transition of an atomic gas, focusing on one prominent universal element of phase transition dynamics: the spontaneous formation of topological defects during a quench through the transition. While the microscopic dynamics of defect formation in phase transitions are generally difficult to investigate, particularly for superfluid phase transitions, Bose-Einstein condensates (BECs) offer unique experimental and theoretical opportunities for probing such details. Although spontaneously formed vortices in the condensation transition have been previously predicted to occur, our results encompass the first experimental observations and statistical characterisation of spontaneous vortex formation in the condensation transition. Using microscopic theories that incorporate atomic interactions and quantum and thermal fluctuations of a finite-temperature Bose gas, we simulate condensation and observe vortex formation in close quantitative agreement with our experimental results. Our studies provide further understanding of the development of coherence in superfluids, and may allow for direct investigation of universal phase-transition dynamics.Comment: 14 pages, 6 figures. Accepted for publication in Nature. Supplementary movie files are available at http://www.physics.uq.edu.au/people/mdavis/spontaneous_vortice

Prostaglandin I2 Signaling Drives Th17 Differentiation and Exacerbates Experimental Autoimmune Encephalomyelitis

BACKGROUND: Prostaglandin I(2) (PGI(2)), a lipid mediator currently used in treatment of human disease, is a critical regulator of adaptive immune responses. Although PGI(2) signaling suppressed Th1 and Th2 immune responses, the role of PGI(2) in Th17 differentiation is not known. METHODOLOGY/PRINCIPAL FINDINGS: In mouse CD4(+)CD62L(+) naïve T cell culture, the PGI(2) analogs iloprost and cicaprost increased IL-17A and IL-22 protein production and Th17 differentiation in vitro. This effect was augmented by IL-23 and was dependent on PGI(2) receptor IP signaling. In mouse bone marrow-derived CD11c(+) dendritic cells (BMDCs), PGI(2) analogs increased the ratio of IL-23/IL-12, which is correlated with increased ability of BMDCs to stimulate naïve T cells for IL-17A production. Moreover, IP knockout mice had delayed onset of a Th17-associated neurological disease, experimental autoimmune encephalomyelitis (EAE), and reduced infiltration of IL-17A-expressing mononuclear cells in the spinal cords compared to wild type mice. These results suggest that PGI(2) promotes in vivo Th17 responses. CONCLUSION: The preferential stimulation of Th17 differentiation by IP signaling may have important clinical implications as PGI(2) and its analogs are commonly used to treat human pulmonary hypertension