310 research outputs found

    Predicting Communication Rates: Efficacy of a Scanning Model

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    Interaction with the surrounding environment is an essential element of ever day life. For individuals' with severe motor and communicative disabilities, single switch scanning is used as method to control their environment and communicate. Despite being very slow, it is often the only option for individuals who cannot use other interfaces. The alteration of timing parameters and scanning system configurations impacts the communication rate of those using single switch scanning. The ability to select and recommend an efficient configuration for an individual with a disability is essential. Predictive models could assist in the goal of achieving the best possible match between user and assistive technology device, but consideration of an individual's single switch scanning tendencies has not been included in communication rate prediction models. Modeling software developed as part of this research study utilizes scan settings, switch settings, error tendencies, error correction strategies, and the matrix configuration to calculate and predict a communication rate. Five participants with disabilities who use single switch scanning were recruited for this study. Participants were asked to transcribe sentences using an on-screen keyboard configured with settings used on their own communication devices. The participant's error types, frequencies, and correction methods were acquired as well as their text entry rate (TER) during sentence transcription. These individual tendencies and system configuration were used as baseline input parameters to a scanning model application that calculated a TER based upon those parameters. The scanning model was used with the participant's tendencies and at least three varied system configurations. Participants were asked to transcribe sentences with these three configurations The predicted TERs of the model were compared to the actual TERs observed during sentence transcription for accuracy. Results showed that prediction were 90% accurate on average. Model TER predictions were less than one character per minute different from observed baseline TER for each participant. Average model predictions for configuration scenarios were less than one character per minute different from observed configuration TER

    Double Flow Refrigeration Compressor Inlet Piping Design and Analysis

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    Case StudyObjective: • Design an inlet piping system for a double flow centrifugal compressor that effectively utilizes existing site spacing constraints: • Distributes flow to each inlet evenly with minimal pressure loss and without gas swirl or other flow disturbances that may cause long term compressor performance and mechanical reliability issues. • Utilizes standard piping components for construction and minimizing piping support structure to minimize capital investment. • Offers simple control methodology eliminating the need for flow control valves and a complicated control system. • Provide most effective design solution with minimal engineering hours and reviews

    Monospecific and bispecific monoclonal SARS-CoV-2 neutralizing antibodies that maintain potency against B.1.617

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    COVID-19 pathogen SARS-CoV-2 has infected hundreds of millions and caused over 5 million deaths to date. Although multiple vaccines are available, breakthrough infections occur especially by emerging variants. Effective therapeutic options such as monoclonal antibodies (mAbs) are still critical. Here, we report the development, cryo-EM structures, and functional analyses of mAbs that potently neutralize SARS-CoV-2 variants of concern. By high-throughput single cell sequencing of B cells from spike receptor binding domain (RBD) immunized animals, we identify two highly potent SARS-CoV-2 neutralizing mAb clones that have single-digit nanomolar affinity and low-picomolar avidity, and generate a bispecific antibody. Lead antibodies show strong inhibitory activity against historical SARS-CoV-2 and several emerging variants of concern. We solve several cryo-EM structures at ~3 Å resolution of these neutralizing antibodies in complex with prefusion spike trimer ectodomain, and reveal distinct epitopes, binding patterns, and conformations. The lead clones also show potent efficacy in vivo against authentic SARS-CoV-2 in both prophylactic and therapeutic settings. We also generate and characterize a humanized antibody to facilitate translation and drug development. The humanized clone also has strong potency against both the original virus and the B.1.617.2 Delta variant. These mAbs expand the repertoire of therapeutics against SARS-CoV-2 and emerging variants

    Natural Host Genetic Resistance to Lentiviral CNS Disease: A Neuroprotective MHC Class I Allele in SIV-Infected Macaques

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    Human immunodeficiency virus (HIV) infection frequently causes neurologic disease even with anti-retroviral treatment. Although associations between MHC class I alleles and acquired immunodeficiency syndrome (AIDS) have been reported, the role MHC class I alleles play in restricting development of HIV-induced organ-specific diseases, including neurologic disease, has not been characterized. This study examined the relationship between expression of the MHC class I allele Mane-A*10 and development of lentiviral-induced central nervous system (CNS) disease using a well-characterized simian immunodeficiency (SIV)/pigtailed macaque model. The risk of developing CNS disease (SIV encephalitis) was 2.5 times higher for animals that did not express the MHC class I allele Mane-A*10 (P = 0.002; RR = 2.5). Animals expressing the Mane-A*10 allele had significantly lower amounts of activated macrophages, SIV RNA, and neuronal dysfunction in the CNS than Mane-A*10 negative animals (P<0.001). Mane-A*10 positive animals with the highest CNS viral burdens contained SIV gag escape mutants at the Mane-A*10-restricted KP9 epitope in the CNS whereas wild type KP9 sequences dominated in the brain of Mane-A*10 negative animals with comparable CNS viral burdens. These concordant findings demonstrate that particular MHC class I alleles play major neuroprotective roles in lentiviral-induced CNS disease

    Toxicity potential of heartwood extractives from two mulberry species against Heterotermes indicola

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    Choice and no-choice tests were run to evaluate natural resistance of the woods of two Morus species (Morus alba and Morus nigra) against the subterranean, by Heterotermes indicola under field conditions. Toxicity, antifeedant and repellency potential of the heartwood extractives was also investigated under laboratory conditions. Heartwood extractives were removed from wood shavings by using methanol or an ethanol: toluene (2:1) mixture. Results of choice and no-choice tests with sap and heartwood blocks exposed to termites, showed that both mulberry species were resistant to termites but in comparison. Morus alba wood was more resistant than Morus nigra to termite feeding as it showed &lt;5 % weight loss after 90 days. Termites exhibited a concentration dependent mortality after exposure to either mulberry species’ heartwood extractives. The highest termite mortality occurred after termites were exposed to filter paper treated with Morus alba extractives at a concentration of 5%. . At this concentration, antifeedancy and repellency were calculated to be 91.67 and 84 %respectively. . Our results also showed that extractives from either mulberry species imparted resistance to vacuum-pressure treated non-durable Populus deltoides wood. Termite mortality was greater than 75 % after feeding on Populus deltoides wood treated with extractives from Morus alba. Solvent only (methanol) treated Populus deltoides controls, showed a minimum weight loss of 2.69 % after 28 days. These results suggest that Morus alba extractives have antitermitic properties and may be potentially useful in the development of environment friendly termiticides

    Plasma deconvolution identifies broadly neutralizing antibodies associated with hepatitis C virus clearance

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    A vaccine for hepatitis C virus (HCV) is urgently needed. Development of broadly neutralizing plasma antibodies during acute infection is associated with HCV clearance, but the viral epitopes of these plasma antibodies are unknown. Identifying these epitopes could define the specificity and function of neutralizing antibodies (NAbs) that should be induced by a vaccine. Here, we present the development and application of a high-throughput method that deconvolutes polyclonal anti-HCV NAbs in plasma, delineating the epitope specificities of anti-HCV NAbs in acute-infection plasma of 44 humans with subsequent clearance or persistence of HCV. Remarkably, we identified multiple broadly neutralizing antibody combinations that were associated with greater plasma neutralizing breadth and with HCV clearance. These studies have the potential to inform new strategies for vaccine development by identifying broadly neutralizing antibody combinations in plasma associated with the natural clearance of HCV, while also providing a high-throughput assay that could identify these responses after vaccination trials

    Coordinated Regulation of SIV Replication and Immune Responses in the CNS

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    Central nervous system (CNS) invasion during acute-stage HIV-infection has been demonstrated in a small number of individuals, but there is no evidence of neurological impairment at this stage and virus infection in brain appears to be controlled until late-stage disease. Using our reproducible SIV macaque model to examine the earliest stages of infection in the CNS, we identified immune responses that differentially regulate inflammation and virus replication in the brain compared to the peripheral blood and lymphoid tissues. SIV replication in brain macrophages and in brain of SIV-infected macaques was detected at 4 days post-inoculation (p.i.). This was accompanied by upregulation of innate immune responses, including IFNβ, IFNβ-induced gene MxA mRNA, and TNFα. Additionally, IL-10, the chemokine CCL2, and activation markers in macrophages, endothelial cells, and astrocytes were all increased in the brain at four days p.i. We observed synchronous control of virus replication, cytokine mRNA levels and inflammatory markers (MHC Class II, CD68 and GFAP) by 14 days p.i.; however, control failure was followed by development of CNS lesions in the brain. SIV infection was accompanied by induction of the dominant-negative isoform of C/EBPβ, which regulates SIV, CCL2, and IL6 transcription, as well as inflammatory responses in macrophages and astrocytes. This synchronous response in the CNS is in part due to the effect of the C/EBPβ on virus replication and cytokine expression in macrophage-lineage cells in contrast to CD4+ lymphocytes in peripheral blood and lymphoid tissues. Thus, we have identified a crucial period in the brain when virus replication and inflammation are controlled. As in HIV-infected individuals, though, this control is not sustained in the brain. Our results suggest that intervention with antiretroviral drugs or anti-inflammatory therapeutics with CNS penetration would sustain early control. These studies further suggest that interventions should target HIV-infected individuals with increased CCL2 levels or HIV RNA in the CNS

    Northeastern united states species treated with copper-based preservatives: Durability in mississippi stake tests

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    This paper reports on the ground-contact durability of lesser-used wood species of the northeastern United States after treatment with copper-based preservatives. Stakes (19 by 19 by 457 mm) cut from balsam-fir (Abies balsamea), eastern hemlock (Tsuga canadensis), eastern spruce (mixture of Picea glauca, Picea mariana and Picea rubens), red maple (Acer rubrum) or eastern white pine (Pinus strobus) were treated with one of four concentrations of chromated copper arsenate type C (CCA-C), copper citrate (CC), alkaline copper quat type C (ACQ-C) or copper azole type A (CBA-A) and placed into the ground at a test site in southern Mississippi. Similarly treated southern pine (Pinus spp.) stakes were included for comparison. The stakes were rated for decay and termite attack after 1, 2, 3, 4, 5, 8, 10 and 12 years. Eastern white pine and incised eastern hemlock and balsam-fir had durability similar to southern pine when treated with CCA or the other copper-based preservatives. Eastern spruce was less durable than the other softwood species, apparently because of low preservative uptake. Red maple had the least durability at all retentions and for all preservatives. This study indicates that several northeastern softwoods can be adequately durable when pressure-treated with CCA-C or copper-based preservatives
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