14 research outputs found

    Sensor Characteristics Reference Guide

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    The Buildings Technologies Office (BTO), within the U.S. Department of Energy (DOE), Office of Energy Efficiency and Renewable Energy (EERE), is initiating a new program in Sensor and Controls. The vision of this program is: • Buildings operating automatically and continuously at peak energy efficiency over their lifetimes and interoperating effectively with the electric power grid. • Buildings that are self-configuring, self-commissioning, self-learning, self-diagnosing, self-healing, and self-transacting to enable continuous peak performance. • Lower overall building operating costs and higher asset valuation. The overarching goal is to capture 30% energy savings by enhanced management of energy consuming assets and systems through development of cost-effective sensors and controls. One step in achieving this vision is the publication of this Sensor Characteristics Reference Guide. The purpose of the guide is to inform building owners and operators of the current status, capabilities, and limitations of sensor technologies. It is hoped that this guide will aid in the design and procurement process and result in successful implementation of building sensor and control systems. DOE will also use this guide to identify research priorities, develop future specifications for potential market adoption, and provide market clarity through unbiased informatio

    Further studies on the synthesis of 24(S),25-epoxycholesterol. A new, efficient preparation of desmosterol

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    Efforts to improve the synthesis of 24(S),25-epoxycholesterol from stigmasterol have included identification of 6α-hydroxy-i-steroid (I) (R1 = OH, R2 = αOH) as a byproduct from the ozonolysis of steroid (II) and an attempt to effect conversion of sulfone I (R1 = SO2Ph, R2 = βOMe) (III) to diol (IV) via Payne rearrangement and nucleophilic trapping of (S)-2-hydroxymethyl-3,3-dimethylepoxide, which led instead to (V) (R3 = α or β OH) (97% yield). A more efficient synthesis of 24(S),25-epoxycholesterol was achieved via coupling of cuprate I (R1 = CuCNLi, R2 = βOMe) (VI) with allylic acetate H2C=CHCMe2OAc to give 73% of I (R1 = CH2CH=CMe2, R2 = βOMe) (VII), in the most efficient conversion yet of a C22 intermediate to desmosterol or its acetate

    Lung and colon cancer detection from CT images using deep learning

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    Cancer is a deadly disease that has gained a reputation as a global health concern. Further, lung cancer has been widely reported as the most deadly cancer type globally, while colon cancer comes second. Meanwhile, early detection is one of the primary ways to prevent lung and colon cancer fatalities. To aid the early detection of lung and colon cancer, we propose a computer-aided diagnostic approach that employs a Deep Learning (DL) architecture to enhance the detection of these cancer types from Computed Tomography (CT) images of suspected body parts. Our experimental dataset (LC25000) contains 25 000 CT images of benign and malignant lung and colon cancer tissues. We used weights from a pre-trained DL architecture for computer vision, EfficientNet, to build and train a lung and colon cancer detection model. EfficientNet is a Convolutional Neural Network architecture that scales all input dimensions such as depth, width, and resolution at the same time. Our research findings showed detection accuracies of 99.63%, 99.50%, and 99.72% for training, validation, and test sets, respectively

    Further studies on synthesis of 24(S),25-epoxycholesterol : new efficient preparation of desmosterol

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    Our synthesis of the regulatory oxysterol 24(S),25-epoxycholesterol (1) from stigmasterol has been improved by the discovery that cuprate 2 can be coupled with allylic acetate 3 to give in 73% yield in the key step of the most effecient conversion yet of a C22 intermediate to desmosteryl acetate (4). Efforts to prep. diol 5 from sulfone 6 via Payne rearrangement of epoxide 7 will also be presented. [on SciFinder(R)

    Neurologic sequelae of COVID-19 are determined by immunologic imprinting from previous coronaviruses

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    Coronavirus disease 2019 (COVID-19), which is caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), remains a global public health emergency. Although SARS-CoV-2 is primarily a respiratory pathogen, extra-respiratory organs, including the central nervous system (CNS), can also be affected. Neurologic symptoms have been observed not only during acute SARS-CoV-2 infection, but also at distance from respiratory disease, also known as long-COVID or neurological post-acute sequelae of COVID-19 (neuroPASC). The pathogenesis of neuroPASC is not well understood, but hypotheses include SARS-CoV-2-induced immune dysfunctions, hormonal dysregulations, and persistence of SARS-CoV-2 reservoirs. In this prospective cohort study, we used a high throughput systems serology approach to dissect the humoral response to SARS-CoV-2 (and other common Coronaviruses - 229E, HKU1, NL63, OC43) in the serum and cerebrospinal fluid (CSF) from 112 infected individuals who developed (n = 18) or did not develop (n = 94) neuroPASC. Unique SARS-CoV-2 humoral profiles were observed in the CSF of neuroPASC, compared to serum responses. All antibody isotypes (IgG, IgM, IgA) and subclasses (IgA1-2; IgG1-4) were detected in serum, whereas CSF was characterized by focused IgG1 (and absence of IgM). These data argue in favor of compartmentalized brain-specific responses against SARS-CoV-2 through selective transfer of antibodies from the serum to the CSF across the blood-brain-barrier, rather than intrathecal synthesis, where more diversity in antibody classes/subclasses would be expected. Compared to individuals who did not develop post-acute complications following infection, individuals with neuroPASC had similar demographic features (median age 65 vs 66.5 years, respectively, p = 0.55; females 33% vs 44%, p = 0.52), but exhibited attenuated systemic antibody responses against SARS-CoV-2, characterized by decreased capacity to activate antibody-dependent complement deposition (ADCD), NK cell activation (ADNKA) and to bind Fcγ receptors. However, surprisingly, neuroPASC individuals showed significantly expanded antibody responses to other common Coronaviruses, including 229E, HKU1, NL63, and OC43. This biased humoral activation across coronaviruses was particularly enriched in neuroPASC individuals with poor outcome, suggesting an original antigenic sin (or immunologic imprinting), where pre-existing immune responses against related viruses shape the response to current infection, as a key prognostic marker of neuroPASC disease. Overall, these findings point to a pathogenic role for compromised anti-SARS-CoV-2 responses in the CSF, likely resulting in incomplete virus clearance from the brain and persistent neuroinflammation, in the development of post-acute neurologic complications of SARS-CoV-2 infection

    Beta-spike-containing boosters induce robust and functional antibody responses to SARS-CoV-2 in macaques primed with distinct vaccines

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    Summary: The reduced effectiveness of COVID-19 vaccines due to the emergence of variants of concern (VOCs) necessitated the use of vaccine boosters to bolster protection against disease. However, it remains unclear how boosting expands protective breadth when primary vaccine platforms are distinct and how boosters containing VOC spike(s) broaden humoral responses. Here, we report that boosters composed of recombinant spike antigens of ancestral (prototype) and Beta VOCs elicit a robust, pan-VOC, and multi-functional humoral response in non-human primates largely independent of the primary vaccine series platform. Interestingly, Beta-spike-containing boosters stimulate immunoglobulin A (IgA) with a greater breadth of recognition in protein-primed recipients when administered with adjuvant system 03 (AS03). Our results highlight the utility of a component-based booster strategy for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) for broad humoral recognition, independent of primary vaccine series. This is of high global health importance given the heterogeneity of primary vaccination platforms distributed

    Functional compartmentalization of antibodies in the central nervous system during chronic HIV infection

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    Abstract The central nervous system (CNS) has emerged as a critical HIV reservoir. Thus, interventions aimed at controlling and eliminating HIV must include CNS-targeted strategies. Given the inaccessibility of the brain, efforts have focused on cerebrospinal fluid (CSF), aimed at defining biomarkers of HIV-disease in the CNS, including HIV-specific antibodies. However, how antibodies traffic between the blood and CNS, and whether specific antibody profiles track with HIV-associated neurocognitive disorders (HAND) remains unclear. Here, we comprehensively profiled HIV-specific antibodies across plasma and CSF from 20 antiretroviral therapy (ART) naive or treated persons with HIV. CSF was populated by IgG1 and IgG3 antibodies, with reduced Fc-effector profiles. While ART improved plasma antibody functional coordination, CSF profiles were unaffected by ART and were unrelated to HAND severity. These data point to a functional sieving of antibodies across the blood-brain barrier, providing previously unappreciated insights for the development of next-generation therapeutics targeting the CNS reservoir.</jats:p
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