5632 research outputs found
Sort by
Label-free differential imaging of cellular components in mouse brain tissue by wide-band photoacoustic microscopy
No full textMapping diverse cellular components with high spatial resolution is important to interrogate biological systems and study disease pathogenesis. Conventional optical imaging techniques for mapping biomolecular profiles with differential staining and labeling methods are cumbersome. Different types of cellular components exhibit distinctive characteristic absorption spectra across a wide wavelength range. By virtue of this property, a lab-made wide-band optical-resolution photoacoustic microscopy (wbOR-PAM) system, which covers wavelengths from the ultraviolet and visible to the shortwave infrared regions, was designed and developed to capture multiple cellular components in 300-μm-thick brain slices at nine different wavelengths without repetitive staining and complicated processing. This wbOR-PAM system provides abundant spectral information. A reflective objective lens with an infinite conjugate design was applied to focus laser beams with different wavelengths, avoiding chromatic aberration. The molecular components of complex brain slices were probed without labeling. The findings of the present study demonstrated a distinctive absorption of phospholipids, a major component of the cell membrane, brain, and nervous system, at 1690 nm and revealed their precise distribution with microscopic resolution in a mouse brain, for the first time. This novel imaging modality provides a new opportunity to investigate important biomolecular components without either labeling or lengthy specimen processing, thus, laying the groundwork for revealing cellular mechanisms involved in disease pathogenesis
Restructuring of olfactory representations in the fly brain around odor relationships in natural sources
No full textA core challenge of olfactory neuroscience is to understand how neural representations of odor are generated and progressively transformed across different layers of the olfactory circuit into formats that support perception and behavior. The encoding of odor by odorant receptors in the input layer of the olfactory system reflects, at least in part, the chemical relationships between odor compounds. Neural representations of odor in higher order associative olfactory areas, generated by random feedforward networks, are expected to largely preserve these input odor relationships. We evaluated these ideas by examining how odors are represented at different stages of processing in the olfactory circuit of the vinegar fly D. melanogaster. We found that representations of odor in the mushroom body (MB), a third-order associative olfactory area in the fly brain, are indeed structured and invariant across flies. However, the structure of MB representational space diverged significantly from what is expected in a randomly connected network. In addition, odor relationships encoded in the MB were better correlated with a metric of the similarity of their distribution across natural sources compared to their similarity with respect to chemical features, and the converse was true for odor relationships encoded in primary olfactory receptor neurons (ORNs). Comparison of odor coding at primary, secondary, and tertiary layers of the circuit revealed that odors were significantly regrouped with respect to their representational similarity across successive stages of olfactory processing, with the largest changes occurring in the MB. The non-linear reorganization of odor relationships in the MB indicates that unappreciated structure exists in the fly olfactory circuit, and this structure may facilitate the generalization of odors with respect to their co-occurence in natural sources
LINKIN-associated proteins necessary for tissue integrity during collective cell migration
No full textCell adhesion plays essential roles in almost every aspect of metazoan biology. Previously, using the developmental migration of the nematode male gonad as a platform, LINKIN (Human: ITFG1,C. elegans: lnkn-1), a relatively understudied transmembrane protein conserved across the metazoa, was found to be necessary for tissue integrity during migration. InC. elegans, loss of lnkn-1 results in the detachment of the lead migratory cell from the rest of the developing male gonad. Three interactors of ITFG1/lnkn-1-RUVBL1/ruvb-1, RUVBL2/ruvb-2, and alpha-tubulin were identified by proteomic analysis using the human HEK293T cells and validated in the nematode male gonad. The ITFG1-RUVBL1 interaction has since been independently validated in a breast cancer cell line model that also implicates the involvement of the pair in metastasis. In this study, we showed that epitope-tagged ITFG1 localized to the cell surface of MDA-MB-231 breast cancer cells. Using unbiased mass spectrometry-based proteomics, we identified a new list of potential interactors of ITFG1. Loss-of-function analysis of their C. elegans orthologs found that three of the interactors - ATP9A/tat-5, NME1/ndk-1, and ANAPC2/apc-2 displayed migratory detachment phenotypes similar to that of lnkn-1. Taken together with the other genes whose reduction of function phenotype is the same as LINKIN (notably cohesion and condensin) suggests the involvement of membrane remodeling and chromosome biology in the tight adhesion dependent on LINKIN, and support the hypothesis for a structure role of chromosomes in post-mitotic cells
The telegraph process is not a subordinator
No full textInvestigations of transcriptional models by Amrhein et al. outline a strategy for connecting steady-state distributions to process dynamics. We clarify its limitations: the strategy holds for a very narrow class of processes, which excludes an example given by the authors
Weak upper-mantle base revealed by postseismic deformation of a deep earthquake
No full textMantle viscosity plays a key role in the Earth’s internal dynamics and thermal history. Geophysical inferences of the viscosity structure, however, have shown large variability depending on the types of observables used or the assumptions imposed. Here, we study the mantle viscosity structure by using the postseismic deformation following a deep (approximately 560 km) earthquake located near the bottom of the upper mantle. We apply independent component analysis to geodetic time series to successfully detect and extract the postseismic deformation induced by the moment magnitude 8.2, 2018 Fiji earthquake. To search for the viscosity structure that can explain the detected signal, we perform forward viscoelastic relaxation modelling with a range of viscosity structures. We find that our observation requires a relatively thin (approximately 100 km), low-viscosity (10¹⁷ to 10¹⁸ Pa s) layer at the bottom of the mantle transition zone. Such a weak zone could explain the slab flattening and orphaning observed in numerous subduction zones, which are otherwise challenging to explain in the whole mantle convection regime. The low-viscosity layer may result from superplasticity induced by the postspinel transition, weak CaSiO₃ perovskite, high water content or dehydration melting
Characterization of Integrase and Excisionase Activity in a Cell-Free Protein Expression System Using a Modeling and Analysis Pipeline
No full textWe present a full-stack modeling, analysis, and parameter identification pipeline to guide the modeling and design of biological systems starting from specifications to circuit implementations and parametrizations. We demonstrate this pipeline by characterizing the integrase and excisionase activity in a cell-free protein expression system. We build on existing Python tools─BioCRNpyler, AutoReduce, and Bioscrape─to create this pipeline. For enzyme-mediated DNA recombination in a cell-free system, we create detailed chemical reaction network models from simple high-level descriptions of the biological circuits and their context using BioCRNpyler. We use Bioscrape to show that the output of the detailed model is sensitive to many parameters. However, parameter identification is infeasible for this high-dimensional model; hence, we use AutoReduce to automatically obtain reduced models that have fewer parameters. This results in a hierarchy of reduced models under different assumptions to finally arrive at a minimal ODE model for each circuit. Then, we run sensitivity analysis-guided Bayesian inference using Bioscrape for each circuit to identify the model parameters. This process allows us to quantify integrase and excisionase activity in cell extracts enabling complex-circuit designs that depend on accurate control over protein expression levels through DNA recombination. The automated pipeline presented in this paper opens up a new approach to complex circuit design, modeling, reduction, and parametrization
Directional Sensitivity of DAS and Its Effect on Rayleigh-Wave Tomography: A Case Study in Oxnard, California
No full textDistributed acoustic sensing (DAS) provides dense arrays ideal for seismic tomography. However, DAS only records average axial strain change along the cable, which can complicate the interpretation of surface-wave observations. With a rectangular DAS array located in the City of Oxnard, California, we compare phase velocity dispersion at the same location illuminated by differently oriented virtual sources. The dispersion curves are consistent for colinear and noncolinear virtual sources, suggesting that surface-wave observations in most of the cross-correlations are dominated by Rayleigh waves. Our measurements confirm that colinear channel pairs provide higher Rayleigh-wave signal-to-noise ratio (SNR). For cross-correlations of noncolinear channel pairs, the travel time of each connecting ray path can still be obtained despite the lower SNR of Rayleigh wave signals. The inverted Rayleigh-wave dispersion map reveals an ancient river channel consistent with the local geologic map. Our results demonstrate the potential of DAS-based 2D surface-wave tomography without special treatment of directional sensitivity in areas where one type of wave is dominating or can be identified
An Earth-sized Planet around an M5 Dwarf Star at 22 pc
No full textWe report on the discovery of an Earth-sized transiting planet (R_p = 1.015 ± 0.051 R_⊕) in a P = 4.02 day orbit around K2-415 (EPIC 211414619), an M5V star at 22 pc. The planet candidate was first identified by analyzing the light-curve data obtained by the K2 mission, and it is here shown to exist in the most recent data from TESS. Combining the light curves with the data secured by our follow-up observations, including high-resolution imaging and near-infrared spectroscopy with IRD, we rule out false-positive scenarios, finding a low false-positive probability of 2 × 10⁻⁴. Based on IRD's radial velocities of K2-415, which were sparsely taken over three years, we obtain a planet mass of 3.0 ± 2.7 M_⊕ (M_p < 7.5 M_⊕ at 95% confidence) for K2-415b. Being one of the lowest-mass stars (≈0.16 M_⊙) known to host an Earth-sized transiting planet, K2-415 will be an interesting target for further follow-up observations, including additional radial velocity monitoring and transit spectroscopy
Trading Throughput for Freshness: Freshness-aware Traffic Engineering and In-Network Freshness Control
No full textWith the advent of the Internet of Things (IoT), applications are becoming increasingly dependent on networks to not only transmit content at high throughput but also deliver it when it is fresh, i.e., synchronized between source and destination. Existing studies have proposed the metric age of information (AoI) to quantify freshness and have system designs that achieve low AoI. However, despite active research in this area, existing results are not applicable to general wired networks for two reasons. First, they focus on wireless settings, where AoI is mostly affected by interference and collision, while queueing issues are more prevalent in wired settings. Second, traditional high-throughput/low-latency legacy drop-adverse (LDA) flows are not taken into account in most system designs; hence, the problem of scheduling mixed flows with distinct performance objectives is not addressed.
In this article, we propose a hierarchical system design to treat wired networks shared by mixed flow traffic, specifically LDA and AoI flows, and study the characteristics of achieving a good tradeoff between throughput and AoI. Our approach to the problem consists of two layers: freshness-aware traffic engineering (FATE) and in-network freshness control (IFC). The centralized FATE solution studies the characteristics of the source flow to derive the sending rate/update frequency for flows via the optimization problem LDA-AoI Coscheduling. The parameters specified by FATE are then distributed to IFC, which is implemented at each outport of the network’s nodes and used for efficient scheduling between LDA and AoI flows. We present a Linux implementation of IFC and demonstrate the effectiveness of FATE/IFC through extensive emulations. Our results show that it is possible to trade a little throughput (5% lower) for much shorter AoI (49% to 71% shorter) compared to state-of-the-art traffic engineering
Near-Body Measurements in Hypersonic Wedge Flows in the T5 Reflected Shock Tunnel by Tunable Diode Laser Absorption Spectroscopy
No full textWe report on spectroscopic measurements of nitric oxide (NO) rotational and vibrational temperatures and concentration in the hypersonic flow fields around two symmetric wedge test models in the Caltech T5 reflected shock tunnel. Three quantum cascade lasers (QCLs), targeting 13 distinct quantum rovibrational transitions of NO, probed the T5 flows at a measurement rate of 50 kHz. Via tunable diode laser absorption spectroscopy (TDLAS), absorption from these rovibrational transitions permitted the path-averaged inferences of temperature and NO concentration both in front of and behind the shocks around the test articles. The fractional proportion of laser absorption in front and behind the shocks was also determined, enabling the measurement of shock locations at several lines of sight in the flow. Two different symmetric wedge test articles were utilized, one characterized by a wedge angle of 48o, and the other 38o. Three different T5 flow conditions were interrogated, a M = 5.5, ∼8 MJ/kg stagnation enthalpy case, a M = 5.3, ∼11 MJ/kg stagnation enthalpy case, and a M = 4.9, ∼18 MJ/kg stagnation enthalpy case. Beam locations were specified relative to the wedge using alignment fins, Cartesian grids of holes which attached rigidly to the model endspans during alignment. The optical configuration allowed for independent characterization of the freestream and post-shock regions. Freestream measurements demonstrate general temperature and NO density decline over the duration of test time, typical of what has been previously measured in T5. Post-shock measurements demonstrate thermal equilibrium at elevated temperatures and high NO densities on the upstream sides of the wedges. Past the vertices of the wedges, post-shock measurements are colder, with thermal non-equilibrium sometimes detected