2,048 research outputs found

    Methods for Control, Calibration, and Performance Optimization of Phased Array Systems

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    Phased array radar systems have proven advantageous in a variety of research applications, offering faster volume scans and unparalleled time-resolution as compared to traditional parabolic dish antenna systems that rely solely on mechanical systems for controlling the direction of radiation. As such, research has accelerated the development of practical phased array systems to realize their full vision. In particular, next generation phased array systems aim to provide additional advantages in the form of re-configurable beam patterns, adaptive digital beamforming, multiple-input multiple-output (MIMO) radar modes, and other software-defined technologies. However, to fully realize a paradigm shift in phased array technology, especially as the ratio of array to sub-array size becomes greater, this requires a corresponding increase in novel digital backend architectures to fully achieve this vision. Therefore, new methods for control, calibration, and performance optimization are required to enable next-generation phased array systems to reach their potential. In this thesis, a variety of practical engineering challenges related to phased array system design are discussed, with system-level implications and relevant theory included where necessary. For instance, for the first time, as explained in this thesis, a GPS disciplined, time-interleaved measurement technique that leveraged real-time control of a beamformer was developed to enable accurate post-processing correction of the phase drift that results from clocking differences between noncoherent physically separated bistatic nodes. In addition, laboratory efficacy of digital predistortion using the memory-polynomial model has been confirmed for the purpose of maximizing an element's usable power while minimizing spectral spreading and achieving desirable output linearity during operation, and a novel method for training predistortion models comprised of a combined software-defined and physical mechanism for measuring transmitter front-end distortion for elements within a digital-at-every element array has been proposed and verified in the lab

    Cost-Comparison of Two Trabecular Micro-Bypass Stents Versus Selective Laser Trabeculoplasty or Medications Only for Intraocular Pressure Control for Patients with Open-Angle Glaucoma

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    Aim: Patients with open-angle glaucoma (OAG) whose intraocular pressure is not adequately controlled by one medication have several treatment options in the US. This analysis evaluated direct costs of unilateral eye treatment with two trabecular micro-bypass stents (two iStents) compared to selective laser trabeculoplasty (SLT) or medications only. Materials and methods: A population-based, annual state-transition, probabilistic, cost-of-care model was used to assess OAG-related costs over 5 years. Patients were modeled to initiate treatment in year zero with two iStents, SLT, or medications only. In years 1–5, patients could remain on initial treatment or move to another treatment option(s), or filtration surgery. Treatment strategy change probabilities were identified by a clinician panel. Direct costs were included for drugs, procedures, and complications. Results: The projected average cumulative cost at 5 years was lower in the two-stent treatment arm (4,420)comparedtotheSLTarm(4,420) compared to the SLT arm (4,730) or medications-only arm (6,217).InitialyearzerocostswerehigherwithtwoiStents(6,217). Initial year-zero costs were higher with two iStents (2,810) than with SLT (842)ormedicationsonly(842) or medications only (996). Average marginal annual costs in years 1–5 were 322fortwoiStents,322 for two iStents, 777 for SLT, and 1,044formedicationsonly.ThecumulativecostdifferencesbetweentwoiStentsvsSLTormedicationsonlydecreasedovertime,withbreakevenby5or3yearspostinitiation,respectively.Byyear5,cumulativesavingswithtwoiStentsoverSLTormedicationsonlywas1,044 for medications only. The cumulative cost differences between two iStents vs SLT or medications only decreased over time, with breakeven by 5 or 3 years post-initiation, respectively. By year 5, cumulative savings with two iStents over SLT or medications only was 309 or $1,797, respectively. Limitations: This analysis relies on clinical expert panel opinion and would benefit from real-world evidence on use of multiple procedures and treatment switching after two-stent treatment, SLT, or polypharmaceutical initial approaches. Conclusions: Despite higher costs in year zero, annual costs thereafter were lowest in the two-stent treatment arm. Two-stent treatment may reduce OAG-related health resource use, leading to direct savings, especially over medications only or at longer time horizons

    Oxygenated Aromatic Compounds are Important Precursors of Secondary Organic Aerosol in Biomass Burning Emissions

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    Biomass burning is the largest combustion-related source of volatile organic compounds (VOCs) to the atmosphere. We describe the development of a state-of-the-science model to simulate the photochemical formation of secondary organic aerosol (SOA) from biomass-burning emissions observed in dry (RH <20%) environmental chamber experiments. The modeling is supported by (i) new oxidation chamber measurements, (ii) detailed concurrent measurements of SOA precursors in biomass-burning emissions, and (iii) development of SOA parameters for heterocyclic and oxygenated aromatic compounds based on historical chamber experiments. We find that oxygenated aromatic compounds, including phenols and methoxyphenols, account for slightly less than 60% of the SOA formed and help our model explain the variability in the organic aerosol mass (R² = 0.68) and O/C (R² = 0.69) enhancement ratios observed across 11 chamber experiments. Despite abundant emissions, heterocyclic compounds that included furans contribute to ∼20% of the total SOA. The use of pyrolysis-temperature-based or averaged emission profiles to represent SOA precursors, rather than those specific to each fire, provide similar results to within 20%. Our findings demonstrate the necessity of accounting for oxygenated aromatics from biomass-burning emissions and their SOA formation in chemical mechanisms

    A Decline in p38 MAPK Signaling Underlies Immunosenescence in Caenorhabditis elegans

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    The decline in immune function with aging, known as immunosenescence, has been implicated in evolutionarily diverse species, but the underlying molecular mechanisms are not understood. During aging in Caenorhabditis elegans, intestinal tissue deterioration and the increased intestinal proliferation of bacteria are observed, but how innate immunity changes during C. elegans aging has not been defined. Here we show that C. elegans exhibits increased susceptibility to bacterial infection with age, and we establish that aging is associated with a decline in the activity of the conserved PMK-1 p38 mitogen-activated protein kinase pathway, which regulates innate immunity in C. elegans. Our data define the phenomenon of innate immunosenescence in C. elegans in terms of the age-dependent dynamics of the PMK-1 innate immune signaling pathway, and they suggest that a cycle of intestinal tissue aging, immunosenescence, and bacterial proliferation leads to death in aging C. elegans

    Long-lived magnetism on chondrite parent bodies

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    publisher: Elsevier articletitle: Long-lived magnetism on chondrite parent bodies journaltitle: Earth and Planetary Science Letters articlelink: http://dx.doi.org/10.1016/j.epsl.2017.07.035 content_type: article copyright: © 2017 The Authors. Published by Elsevier B.V.© 2017 The Authors. Published by Elsevier B.V. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/). The attached file is the published version of the article

    Combining the Tyrosine Kinase Inhibitor Cabozantinib and the mTORC1/2 Inhibitor Sapanisertib Blocks ERK Pathway Activity and Suppresses Tumor Growth in Renal Cell Carcinoma.

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    UNLABELLED: Current treatment approaches for renal cell carcinoma (RCC) face challenges in achieving durable tumor responses due to tumor heterogeneity and drug resistance. Combination therapies that leverage tumor molecular profiles could offer an avenue for enhancing treatment efficacy and addressing the limitations of current therapies. To identify effective strategies for treating RCC, we selected ten drugs guided by tumor biology to test in six RCC patient-derived xenograft (PDX) models. The multitargeted tyrosine kinase inhibitor (TKI) cabozantinib and mTORC1/2 inhibitor sapanisertib emerged as the most effective drugs, particularly when combined. The combination demonstrated favorable tolerability and inhibited tumor growth or induced tumor regression in all models, including two from patients who experienced treatment failure with FDA-approved TKI and immunotherapy combinations. In cabozantinib-treated samples, imaging analysis revealed a significant reduction in vascular density, and single-nucleus RNA sequencing (snRNA-seq) analysis indicated a decreased proportion of endothelial cells in the tumors. SnRNA-seq data further identified a tumor subpopulation enriched with cell-cycle activity that exhibited heightened sensitivity to the cabozantinib and sapanisertib combination. Conversely, activation of the epithelial-mesenchymal transition pathway, detected at the protein level, was associated with drug resistance in residual tumors following combination treatment. The combination effectively restrained ERK phosphorylation and reduced expression of ERK downstream transcription factors and their target genes implicated in cell-cycle control and apoptosis. This study highlights the potential of the cabozantinib plus sapanisertib combination as a promising treatment approach for patients with RCC, particularly those whose tumors progressed on immune checkpoint inhibitors and other TKIs. SIGNIFICANCE: The molecular-guided therapeutic strategy of combining cabozantinib and sapanisertib restrains ERK activity to effectively suppress growth of renal cell carcinomas, including those unresponsive to immune checkpoint inhibitors

    Cancer Genome Sequencing and Its Implications for Personalized Cancer Vaccines

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    New DNA sequencing platforms have revolutionized human genome sequencing. The dramatic advances in genome sequencing technologies predict that the $1,000 genome will become a reality within the next few years. Applied to cancer, the availability of cancer genome sequences permits real-time decision-making with the potential to affect diagnosis, prognosis, and treatment, and has opened the door towards personalized medicine. A promising strategy is the identification of mutated tumor antigens, and the design of personalized cancer vaccines. Supporting this notion are preliminary analyses of the epitope landscape in breast cancer suggesting that individual tumors express significant numbers of novel antigens to the immune system that can be specifically targeted through cancer vaccines
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