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At least 109 records · Page 6

Rapid Chemometric Filtering of Spectral Data

A method of rapid, programmable filtering of spectral transmittance, reflectance, or fluorescence data to measure the concentrations of chemical species has been proposed. By programmable is meant that a variety of spectral analyses can readily be performed and modified in software, firmware, and/or electronic hardware, without need to change optical filters or other optical hardware of the associated spectrometers. The method is intended to enable real-time identification of single or multiple target chemical species in applications that involve high-throughput screening of multiple samples. Examples of such applications include (but are not limited to) combinatorial chemistry, flow cytometry, bead assays, testing drugs, remote sensing, and identification of targets. The basic concept of the proposed method is to perform real-time crosscorrelations of a measured spectrum with one or more analytical function(s) of wavelength that could be, for example, the known spectra of target species. Assuming that measured spectral intensities are proportional to concentrations of target species plus background spectral intensities, then after subtraction of background levels, it should be possible to determine target species concentrations from cross-correlation values. Of course, the problem of determining the concentrations is more complex when spectra of different species overlap, but the problem can be solved by use of multiple analytical functions in combination with computational techniques that have been developed previously for analyses of this type. The method is applicable to the design and operation of a spectrometer in which spectrally dispersed light is measured by means of an active-pixel sensor (APS) array. The row or column dimension of such an array is generally chosen to be aligned along the spectral-dispersion dimension, so that each pixel intercepts light in a narrow spectral band centered on a wavelength that is a known function of the pixel position. The proposed method admits of two hardware implementations for computing cross-correlations in real time.

Beaman, Gregory↗

Coherent Doppler lidar for automated space vehicle rendezvous, stationkeeping and capture

The inherent spatial resolution of laser radar makes ladar or lidar an attractive candidate for Automated Rendezvous and Capture application. Previous applications were based on incoherent lidar techniques, requiring retro-reflectors on the target vehicle. Technology improvements (reduced size, no cryogenic cooling requirement) have greatly enhanced the construction of coherent lidar systems. Coherent lidar permits the acquisition of non-cooperative targets at ranges that are limited by the detection capability rather than by the signal-to-noise ratio (SNR) requirements. The sensor can provide translational state information (range, velocity, and angle) by direct measurement and, when used with any array detector, also can provide attitude information by Doppler imaging techniques. Identification of the target is accomplished by scanning with a high pulse repetition frequency (dependent on the SNR). The system performance is independent of range and should not be constrained by sun angle. An initial effort to characterize a multi-element detection system has resulted in a system that is expected to work to a minimum range of 1 meter. The system size, weight and power requirements are dependent on the operating range; 10 km range requires a diameter of 3 centimeters with overall size at 3 x 3 x 15 to 30 cm, while 100 km range requires a 30 cm diameter.

Bilbro, James A.↗

Method and apparatus for determining time, direction, and composition of impacting space particles

A space particle collector for recording the time specific particles are captured, and its direction at the time of capture, utilizes an array of targets, each comprised of an MOS capacitor on a chip charged from an external source and discharged upon impact by a particle through a tab on the chip that serves as a fuse. Any impacting particle creates a crater, but only the first will cause a discharge of the capacitor. A substantial part of the metal film around the first crater is burned off by the discharge current. The time of the impulse which burns the tab, and the identification of the target, is recorded together with data from flight instruments. The metal film is partitioned into pie sections to provide a plurality of targets on each of an array of silicon wafers, thus increasing the total number of identified particles that can be collected. It is thus certain which particles were captured at what specific times.

Kinard, William H.↗

Prioritizing Scientific Data for Transmission

A software system has been developed for prioritizing newly acquired geological data onboard a planetary rover. The system has been designed to enable efficient use of limited communication resources by transmitting the data likely to have the most scientific value. This software operates onboard a rover by analyzing collected data, identifying potential scientific targets, and then using that information to prioritize data for transmission to Earth. Currently, the system is focused on the analysis of acquired images, although the general techniques are applicable to a wide range of data modalities. Image prioritization is performed using two main steps. In the first step, the software detects features of interest from each image. In its current application, the system is focused on visual properties of rocks. Thus, rocks are located in each image and rock properties, such as shape, texture, and albedo, are extracted from the identified rocks. In the second step, the features extracted from a group of images are used to prioritize the images using three different methods: (1) identification of key target signature (finding specific rock features the scientist has identified as important), (2) novelty detection (finding rocks we haven t seen before), and (3) representative rock sampling (finding the most average sample of each rock type). These methods use techniques such as K-means unsupervised clustering and a discrimination-based kernel classifier to rank images based on their interest level.

Castano, Rebecca↗

A Proposal for an Integrated Geophysical Strategy to "Follow the Water" on Mars

The search for subsurface water has become a primary focus of Mars exploration. Its abundance and distribution (both as ground ice and groundwater) have important implications for understanding the geologic, hydrologic, and climatic evolution of the planet; the potential origin and continued survival of life; and the accessibility of a critical in situ resource for sustaining future human explorers. For these reasons, a principal goal of the Mars science, astrobiology, and the HEDS programs is to determine the 3-D distribution and state of subsurface H2O, at a resolution sufficient to permit reaching any desired volatile target by drilling. The three targets most often discussed are: groundwater, massive deposits of near-surface ground ice (associated with the ponded discharge of the outflow channels or the relic of a former ocean), and ice-saturated frozen ground. Based on the present best estimates of mean annual surface temperature, crustal thermal conductivity, geothermal heat flow, and groundwater freezing temperature, the mean thickness of frozen ground on Mars is expected to vary from approx. = 2.5 - 5 km at the equator to approx. = 6.5 - 13 km at the poles. However, natural variations in both crustal heat flow and thermal conductivity are likely to result in significant local departures from these predicted values. The recent discovery of "young" fluvial-like features, emanating from the slopes of local scarps, raises the possibility that liquid water may also exist episodically at shallow (approx. = 100 - 500 m) depth; however, the true nature and absolute age of these features remains highly uncertain. Although the belief that Mars is water-rich is supported by a wide variety geologic evidence, our ignorance about the heterogeneous nature and thermal evolution of the planet's crust effectively precludes geomorphic or theoretical attempts to quantitatively assess the current geographic and subsurface vertical distribution of ground ice and groundwater . For this reason, any exploration activity (such as drilling) whose success is contingent on the presence of subsurface water, must be preceded by a comprehensive high-resolution geophysical survey capable of assessing whether local reservoirs of water and ice actually exist. Terrestrial experience has demonstrated that the accurate identification of such targets is likely to require the application of multiple geophysical techniques. In this abstract we propose an integrated strategy for the geophysical exploration of Mars that we believe represents the fastest, most cost-effect, and technically capable approach to identifying the state and distribution of subsurface water. Additional information is contained in the original extended abstract.

Clifford, S. M.↗

Synthetic data-driven deep learning for label-free autonomous atomic force microscopy

Atomic force microscopy (AFM) is a widely used tool for nanoscale characterization across materials science, energy research, and biology. However, its adoption in high-throughput materials discovery and statistically driven studies remains limited by a strong dependence on expert operator input and by the scarcity of annotated experimental AFM datasets needed to enable data-driven automation. Here, we introduce SimuScan, a synthetic-data–driven framework that enables reliable AFM feature identification, segmentation, and targeted imaging without requiring large manually labeled experimental datasets. SimuScan generates tunable, high-fidelity synthetic AFM images of defined morphologies while incorporating realistic experimental artifacts, including tip–sample convolution, noise, flattening distortions, and surface debris. These datasets are shown to support scalable, label-free training of modern deep learning models for AFM analysis. When integrated into data-driven AFM workflows, SimuScan-trained models can locate and analyze nanoscale structures across large datasets and guide targeted follow-up imaging. We validate this approach on nanostructured surfaces, DNA assemblies, and bacterial cells, demonstrating robust generalization across diverse sample types with minimal operator intervention. More broadly, this work establishes a general strategy for generating explicitly conditioned, task-relevant synthetic data to improve the reliability of downstream models in autonomous microscopy.

Millan-Solsona, Ruben [Oak Ridge National Laborato↗

Integrated fluorescence light microscopy-guided cryo-focused ion beam-milling for in situ montage cryo-ET

Cryogenic-electron tomography (cryo-ET) permits the in situ visualization of biological macromolecules at the molecular level. Owing to the variable thickness of cells, tissues and organisms, frozen specimens may need to be thinned by cryo-focused ion beam (FIB) milling to produce thin (<500 nm) cryo-lamellae suitable for cryo-ET. Locating regions of interest remains a challenge because untargeted milling can lead to inadvertent ablation and removal of regions of interest. Correlative light and electron microscopy, combined with cryo-FIB milling, can guide the identification of labeled targets in the cellular milieu. Multiple transfers between cryo-imaging instruments, cumbersome correlation algorithms, limited accuracy and low throughput have hindered the routine adoption of cryo-FIB milling within a multimodal correlative workflow for in situ structural biology. Here, in this study, we present a workflow for 3D correlative cryo-fluorescence light microscopy-FIB-ET that streamlines fluorescence light microscopy-guided FIB milling, improving throughput while preserving both structural and contextual information. The complete integration of hardware and software described here minimizes sample contamination from cross-platform exchanges and greatly enhances the efficiency of 3D targeting in cryo-milling. We then describe procedures for implementing montage parallel array cryo-ET (MPACT), which can be easily adapted to any modern life-science transmission electron microscope. MPACT supports high-throughput cryo-ET acquisitions (10 tilt series in 1.5 h) for structure determination and comprehensive contextual understanding of macromolecules within their native surroundings. A complete session from sample preparation to MPACT data processing takes 5−7 d for an individual experienced in both cryo-EM and cryo-FIB milling.

Yang, Jie E. [Univ. of Wisconsin, Madison, WI (Uni↗

Enzalutamide response in a panel of prostate cancer cell lines reveals a role for glucocorticoid receptor in enzalutamide resistant disease

Representative in vitro model systems that accurately model response to therapy and allow the identification of new targets are important for improving our treatment of prostate cancer. Here we describe molecular characterization and drug testing in a panel of 20 prostate cancer cell lines. The cell lines cluster into distinct subsets based on RNA expression, which is largely driven by functional Androgen Receptor (AR) expression. KLK3 , the AR-responsive gene that encodes prostate specific antigen, shows the greatest variability in expression across the cell line panel. Other common prostate cancer associated genes such as TMPRSS2 and ERG show similar expression patterns. Copy number analysis demonstrates that many of the most commonly gained (including regions containing TERC and MYC ) and lost regions (including regions containing TP53 and PTEN) that were identified in patient samples by the TCGA are mirrored in the prostate cancer cell lines. Assessment of response to the anti-androgen enzalutamide shows a distinct separation of responders and non-responders, predominantly related to status of wild-type AR. Surprisingly, several AR-null lines responded to enzalutamide. These AR-null, enzalutamide-responsive cells were characterized by high levels of expression of glucocorticoid receptor (GR) encoded by NR3C1 . Treatment of these cells with the anti-GR agent mifepristone showed that they were more sensitive to this drug than enzalutamide, as were several of the enzalutamide non-responsive lines. This is consistent with several recent reports that suggest that GR expression is an alternative signaling mechanism that can bypass AR blockade. This study reinforces the utility of large cell line panels for the study of cancer and identifies several cell lines that represent ideal models to study AR-null cells that have upregulated GR to sustain growth.

59 BASIC BIOLOGICAL SCIENCES↗

An emerging multi-omic understanding of the genetics of opioid addiction

Opioid misuse, addiction, and associated overdose deaths remain global public health crises. Despite the tremendous need for pharmacological treatments, current options are limited in number, use, and effectiveness. Fundamental leaps forward in our understanding of the biology driving opioid addiction are needed to guide development of more effective medication-assisted therapies. This Review focuses on the omics-identified biological features associated with opioid addiction. Recent GWAS have begun to identify robust genetic associations, including variants in OPRM1, FURIN, and the gene cluster SCAI/PPP6C/RABEPK. An increasing number of omics studies of postmortem human brain tissue examining biological features (e.g., histone modification and gene expression) across different brain regions have identified broad gene dysregulation associated with overdose death among opioid misusers. Drawn together by meta-analysis and multi-omic systems biology, and informed by model organism studies, key biological pathways enriched for opioid addiction–associated genes are emerging, which include specific receptors (e.g., GABAB receptors, GPCR, and Trk) linked to signaling pathways (e.g., Trk, ERK/MAPK, orexin) that are associated with synaptic plasticity and neuronal signaling. Studies leveraging the agnostic discovery power of omics and placing it within the context of functional neurobiology will propel us toward much-needed, field-changing breakthroughs, including identification of actionable targets for drug development to treat this devastating brain disease.

60 APPLIED LIFE SCIENCES↗

Multi-omics data compendium of pancreatic islet and β cell responses to pro-inflammatory cytokines

In type 1 diabetes (T1D), autoimmune response and inflammation cause the death of pancreatic ß cells, leading to the body’s inability to produce insulin and maintain glucose homeostasis. This process is at least in part mediated by pro-inflammatory cytokines, such as interferon (IFN)a, IFN?, interleukin (IL)-1ß, and tumor necrosis factor (TNF)a, which induce ß-cell dysfunction and apoptosis. A deep understanding of the ß-cell signaling and regulatory networks induced by these cytokines could lead to the identification of therapeutic targets to prevent T1D development. To study cytokine-mediated islets/ß-cell signaling and regulatory networks, a variety of omics experiments have been conducted, including transcriptomics, epigenomics (DNA methylation, UMI-4C, ATAC-seq & ChIP-seq), proteomics (bottom-up, top-down, post-translational modification analysis), lipidomics, and metabolomics. The combination of these datasets can be instrumental in identifying signaling components and regulatory factors involved in ß-cell stress/death. Here, we aggregated these multiple omics datasets into a centralized location, providing a quality-controlled and statistically rigorous resource for investigators seeking to holistically study ß-cell regulation by pro-inflammatory cytokines.

Sarkar, Soumyadeep [Pacific Northwest National Lab↗

Multi-omics data compendium: Data package 10 (Pck010)

In type 1 diabetes (T1D), autoimmune response and inflammation cause the death of pancreatic ß cells, leading to the body’s inability to produce insulin and maintain glucose homeostasis. This process is at least in part mediated by pro-inflammatory cytokines, such as interferon (IFN)a, IFN?, interleukin (IL)-1ß, and tumor necrosis factor (TNF)a, which induce ß-cell dysfunction and apoptosis. A deep understanding of the ß-cell signaling and regulatory networks induced by these cytokines could lead to the identification of therapeutic targets to prevent T1D development. To study cytokine-mediated islets/ß-cell signaling and regulatory networks, a variety of omics experiments have been conducted, including transcriptomics, epigenomics (DNA methylation, UMI-4C, ATAC-seq & ChIP-seq), proteomics (bottom-up, top-down, post-translational modification analysis), lipidomics, and metabolomics. The combination of these datasets can be instrumental in identifying signaling components and regulatory factors involved in ß-cell stress/death. Here, we aggregated these multiple omics datasets into a centralized location, providing a quality-controlled and statistically rigorous resource for investigators seeking to holistically study ß-cell regulation by pro-inflammatory cytokines.

Sarkar, Soumyadeep [Pacific Northwest National Lab↗

Multi-omics data compendium: Data package 11 (Pck011)

In type 1 diabetes (T1D), autoimmune response and inflammation cause the death of pancreatic ß cells, leading to the body’s inability to produce insulin and maintain glucose homeostasis. This process is at least in part mediated by pro-inflammatory cytokines, such as interferon (IFN)a, IFN?, interleukin (IL)-1ß, and tumor necrosis factor (TNF)a, which induce ß-cell dysfunction and apoptosis. A deep understanding of the ß-cell signaling and regulatory networks induced by these cytokines could lead to the identification of therapeutic targets to prevent T1D development. To study cytokine-mediated islets/ß-cell signaling and regulatory networks, a variety of omics experiments have been conducted, including transcriptomics, epigenomics (DNA methylation, UMI-4C, ATAC-seq & ChIP-seq), proteomics (bottom-up, top-down, post-translational modification analysis), lipidomics, and metabolomics. The combination of these datasets can be instrumental in identifying signaling components and regulatory factors involved in ß-cell stress/death. Here, we aggregated these multiple omics datasets into a centralized location, providing a quality-controlled and statistically rigorous resource for investigators seeking to holistically study ß-cell regulation by pro-inflammatory cytokines.

Sarkar, Soumyadeep [Pacific Northwest National Lab↗

Multi-omics data compendium: Data package 12 (Pck012)

In type 1 diabetes (T1D), autoimmune response and inflammation cause the death of pancreatic ß cells, leading to the body’s inability to produce insulin and maintain glucose homeostasis. This process is at least in part mediated by pro-inflammatory cytokines, such as interferon (IFN)a, IFN?, interleukin (IL)-1ß, and tumor necrosis factor (TNF)a, which induce ß-cell dysfunction and apoptosis. A deep understanding of the ß-cell signaling and regulatory networks induced by these cytokines could lead to the identification of therapeutic targets to prevent T1D development. To study cytokine-mediated islets/ß-cell signaling and regulatory networks, a variety of omics experiments have been conducted, including transcriptomics, epigenomics (DNA methylation, UMI-4C, ATAC-seq & ChIP-seq), proteomics (bottom-up, top-down, post-translational modification analysis), lipidomics, and metabolomics. The combination of these datasets can be instrumental in identifying signaling components and regulatory factors involved in ß-cell stress/death. Here, we aggregated these multiple omics datasets into a centralized location, providing a quality-controlled and statistically rigorous resource for investigators seeking to holistically study ß-cell regulation by pro-inflammatory cytokines.

Sarkar, Soumyadeep [Pacific Northwest National Lab↗

Multi-omics data compendium: Data package 13 (Pck013)

In type 1 diabetes (T1D), autoimmune response and inflammation cause the death of pancreatic ß cells, leading to the body’s inability to produce insulin and maintain glucose homeostasis. This process is at least in part mediated by pro-inflammatory cytokines, such as interferon (IFN)a, IFN?, interleukin (IL)-1ß, and tumor necrosis factor (TNF)a, which induce ß-cell dysfunction and apoptosis. A deep understanding of the ß-cell signaling and regulatory networks induced by these cytokines could lead to the identification of therapeutic targets to prevent T1D development. To study cytokine-mediated islets/ß-cell signaling and regulatory networks, a variety of omics experiments have been conducted, including transcriptomics, epigenomics (DNA methylation, UMI-4C, ATAC-seq & ChIP-seq), proteomics (bottom-up, top-down, post-translational modification analysis), lipidomics, and metabolomics. The combination of these datasets can be instrumental in identifying signaling components and regulatory factors involved in ß-cell stress/death. Here, we aggregated these multiple omics datasets into a centralized location, providing a quality-controlled and statistically rigorous resource for investigators seeking to holistically study ß-cell regulation by pro-inflammatory cytokines.

Sarkar, Soumyadeep [Pacific Northwest National Lab↗

Multi-omics data compendium: Data package 14 (Pck014)

In type 1 diabetes (T1D), autoimmune response and inflammation cause the death of pancreatic ß cells, leading to the body’s inability to produce insulin and maintain glucose homeostasis. This process is at least in part mediated by pro-inflammatory cytokines, such as interferon (IFN)a, IFN?, interleukin (IL)-1ß, and tumor necrosis factor (TNF)a, which induce ß-cell dysfunction and apoptosis. A deep understanding of the ß-cell signaling and regulatory networks induced by these cytokines could lead to the identification of therapeutic targets to prevent T1D development. To study cytokine-mediated islets/ß-cell signaling and regulatory networks, a variety of omics experiments have been conducted, including transcriptomics, epigenomics (DNA methylation, UMI-4C, ATAC-seq & ChIP-seq), proteomics (bottom-up, top-down, post-translational modification analysis), lipidomics, and metabolomics. The combination of these datasets can be instrumental in identifying signaling components and regulatory factors involved in ß-cell stress/death. Here, we aggregated these multiple omics datasets into a centralized location, providing a quality-controlled and statistically rigorous resource for investigators seeking to holistically study ß-cell regulation by pro-inflammatory cytokines.

Sarkar, Soumyadeep [Pacific Northwest National Lab↗

Multi-omics data compendium: Data package 15 (Pck015)

In type 1 diabetes (T1D), autoimmune response and inflammation cause the death of pancreatic ß cells, leading to the body’s inability to produce insulin and maintain glucose homeostasis. This process is at least in part mediated by pro-inflammatory cytokines, such as interferon (IFN)a, IFN?, interleukin (IL)-1ß, and tumor necrosis factor (TNF)a, which induce ß-cell dysfunction and apoptosis. A deep understanding of the ß-cell signaling and regulatory networks induced by these cytokines could lead to the identification of therapeutic targets to prevent T1D development. To study cytokine-mediated islets/ß-cell signaling and regulatory networks, a variety of omics experiments have been conducted, including transcriptomics, epigenomics (DNA methylation, UMI-4C, ATAC-seq & ChIP-seq), proteomics (bottom-up, top-down, post-translational modification analysis), lipidomics, and metabolomics. The combination of these datasets can be instrumental in identifying signaling components and regulatory factors involved in ß-cell stress/death. Here, we aggregated these multiple omics datasets into a centralized location, providing a quality-controlled and statistically rigorous resource for investigators seeking to holistically study ß-cell regulation by pro-inflammatory cytokines.

Sarkar, Soumyadeep [Pacific Northwest National Lab↗

Multi-omics data compendium: Data package 16 (Pck016)

In type 1 diabetes (T1D), autoimmune response and inflammation cause the death of pancreatic ß cells, leading to the body’s inability to produce insulin and maintain glucose homeostasis. This process is at least in part mediated by pro-inflammatory cytokines, such as interferon (IFN)a, IFN?, interleukin (IL)-1ß, and tumor necrosis factor (TNF)a, which induce ß-cell dysfunction and apoptosis. A deep understanding of the ß-cell signaling and regulatory networks induced by these cytokines could lead to the identification of therapeutic targets to prevent T1D development. To study cytokine-mediated islets/ß-cell signaling and regulatory networks, a variety of omics experiments have been conducted, including transcriptomics, epigenomics (DNA methylation, UMI-4C, ATAC-seq & ChIP-seq), proteomics (bottom-up, top-down, post-translational modification analysis), lipidomics, and metabolomics. The combination of these datasets can be instrumental in identifying signaling components and regulatory factors involved in ß-cell stress/death. Here, we aggregated these multiple omics datasets into a centralized location, providing a quality-controlled and statistically rigorous resource for investigators seeking to holistically study ß-cell regulation by pro-inflammatory cytokines.

Sarkar, Soumyadeep [Pacific Northwest National Lab↗

Multi-omics data compendium: Data package 17 (Pck017)

In type 1 diabetes (T1D), autoimmune response and inflammation cause the death of pancreatic ß cells, leading to the body’s inability to produce insulin and maintain glucose homeostasis. This process is at least in part mediated by pro-inflammatory cytokines, such as interferon (IFN)a, IFN?, interleukin (IL)-1ß, and tumor necrosis factor (TNF)a, which induce ß-cell dysfunction and apoptosis. A deep understanding of the ß-cell signaling and regulatory networks induced by these cytokines could lead to the identification of therapeutic targets to prevent T1D development. To study cytokine-mediated islets/ß-cell signaling and regulatory networks, a variety of omics experiments have been conducted, including transcriptomics, epigenomics (DNA methylation, UMI-4C, ATAC-seq & ChIP-seq), proteomics (bottom-up, top-down, post-translational modification analysis), lipidomics, and metabolomics. The combination of these datasets can be instrumental in identifying signaling components and regulatory factors involved in ß-cell stress/death. Here, we aggregated these multiple omics datasets into a centralized location, providing a quality-controlled and statistically rigorous resource for investigators seeking to holistically study ß-cell regulation by pro-inflammatory cytokines.

Sarkar, Soumyadeep [Pacific Northwest National Lab↗