Magnetic Bearings at Draper Laboratory

Magnetic bearings, unlike traditional mechanical bearings, consist of a series of components mated together to form a stabilized system. The correct design of the actuator and sensor will provide a cost effective device with low power requirements. The proper choice of a control system utilizes the variables necessary to control the system in an efficient manner. The specific application will determine the optimum design of the magnetic bearing system including the touch down bearing. Draper for the past 30 years has been a leader in all these fields. This paper summarizes the results carried out at Draper in the field of magnetic bearing development. A 3-D radial magnetic bearing is detailed in this paper. Data obtained from recently completed projects using this design are included. One project was a high radial load (1000 pound) application. The second was a high speed (35,000 rpm), low loss flywheel application. The development of a low loss axial magnetic bearing is also included in this paper

SERT: A Transfomer Based Model for Spatio-Temporal Sensor Data with Missing Values for Environmental Monitoring

Environmental monitoring is crucial to our understanding of climate change, biodiversity loss and pollution. The availability of large-scale spatio-temporal data from sources such as sensors and satellites allows us to develop sophisticated models for forecasting and understanding key drivers. However, the data collected from sensors often contain missing values due to faulty equipment or maintenance issues. The missing values rarely occur simultaneously leading to data that are multivariate misaligned sparse time series. We propose two models that are capable of performing multivariate spatio-temporal forecasting while handling missing data naturally without the need for imputation. The first model is a transformer-based model, which we name SERT (Spatio-temporal Encoder Representations from Transformers). The second is a simpler model named SST-ANN (Sparse Spatio-Temporal Artificial Neural Network) which is capable of providing interpretable results. We conduct extensive experiments on two different datasets for multivariate spatio-temporal forecasting and show that our models have competitive or superior performance to those at the state-of-the-art.Comment: 11 pages, 7 figure

Mechanisms for Controlling HIV-1 Infection: A Gene Therapy Approach

Current anti-retroviral treatment (ART) for HIV-1 is highly effectively at controlling the infection. However, during early infection the virus establishes a latent reservoir, which is not impacted by ART. Any treatment interruption rapidly results in virus rebound from the latent reservoir to pre-therapy levels and thus ART does not constitute an HIV-1 cure. Alternate treatments are currently being explored in the form of gene therapy, following the success of the Berlin patient who has had undetectable virus since 2007. This review will describe the contrasting cure approaches that are currently the focus of multiple studies to control HIV, then focus in on functional cure gene therapy strategies; specifically, epigenetic silencing of HIV-1 by various methods, including RNA-directed transcriptional gene silencing. The various delivery strategies for targeting cells of the latent reservoir will be reviewed and finally, the clinical status and current challenges for ex vivo versus in vivo gene therapy delivery approaches will be discussed

Characterization of time-resolved laser differential phase using 3D complementary cumulative distribution functions

An experimental method for characterizing the time-resolved phase noise of a fast switching tunable laser is discussed. The method experimentally determines a complementary cumulative distribution function of the laser's differential phase as a function of time after a switching event. A time resolved bit error rate of differential quadrature phase shift keying formatted data, calculated using the phase noise measurements, was fitted to an experimental time-resolved bit error rate measurement using a field programmable gate array, finding a good agreement between the time-resolved bit error rates

Phenotypic and functional characteristics of highly differentiated CD57 +NKG2C + NK cells in HIV-1- infected individuals

Natural killer (NK) cells are important anti-viral effector cells. The function and phenotype of the NK cells that constitute an individual’s NK cell repertoire can be influenced by ongoing and/or previous viral infections. Indeed, infection with human cytomegalovirus (HCMV) drives the expansion of a highly differentiated NK cell population characterized by expression of CD57 and the activating NKG2C receptor. This NK cell population has also been noted to occur in HIV-1-infected individuals. We evaluated the NK cells of HIV-1-infected and –uninfected individuals to determine the relative frequency of highly differentiated CD57 +NKG2C + NK cells and characterize these cells for their receptor expression and responsiveness to diverse stimuli. Highly differentiated CD57 +NKG2C + NK cells occurred at higher frequencies in HCMV-infected donors relative to HCMV-uninfected donors and were dramatically expanded in HIV-1/HCMV co-infected donors. The expanded CD57 +NKG2C + NK cell population in HIV-1-infected donors remained stable following antiretroviral therapy. CD57 +NKG2C + NK cells derived from HIV-1-infected individuals were robustly activated by antibody-dependent stimuli that contained anti-HIV-1 antibodies or therapeutic anti-CD20 antibody, and these NK cells mediated cytolysis through NKG2C. Lastly, CD57 +NKG2C + NK cells from HIV-1-infected donors were characterized by reduced expression of the inhibitory NKG2A receptor. The abundance of highly functional CD57 +NKG2C + NK cells in HIV-1-infected individuals raises the possibility that these NK cells could play a role in HIV-1 pathogenesis or serve as effector cells for therapeutic/cure strategies

T Follicular Helper Cells Have Distinct Modes of Migration and Molecular Signatures in Naive and Memory Immune Responses

SummaryB helper follicular T (Tfh) cells are critical for long-term humoral immunity. However, it remains unclear how these cells are recruited and contribute to secondary immune responses. Here we show that primary Tfh cells segregate into follicular mantle (FM) and germinal center (GC) subpopulations that display distinct gene expression signatures. Restriction of the primary Tfh cell subpopulation in the GC was mediated by downregulation of chemotactic receptor EBI2. Following collapse of the GC, memory T cells persisted in the outer follicle where they scanned CD169+ subcapsular sinus macrophages. Reactivation and intrafollicular expansion of these follicular memory T cells in the subcapsular region was followed by their extrafollicular dissemination via the lymphatic flow. These data suggest that Tfh cells integrate their antigen-experience history to focus T cell help within the GC during primary responses but act rapidly to provide systemic T cell help after re-exposure to the antigen

Circulating gluten-specific FOXP3 + CD39 + regulatory T cells have impaired suppressive function in patients with celiac disease

Background Celiac disease is a chronic immune-mediated inflammatory disorder of the gut triggered by dietary gluten. Although the effector T-cell response in patients with celiac disease has been well characterized, the role of regulatory T (Treg) cells in the loss of tolerance to gluten remains poorly understood. Objective We sought to define whether patients with celiac disease have a dysfunction or lack of gluten-specific forkhead box protein 3 (FOXP3)+ Treg cells. Methods Treated patients with celiac disease underwent oral wheat challenge to stimulate recirculation of gluten-specific T cells. Peripheral blood was collected before and after challenge. To comprehensively measure the gluten-specific CD4+ T-cell response, we paired traditional IFN-γ ELISpot with an assay to detect antigen-specific CD4+ T cells that does not rely on tetramers, antigen-stimulated cytokine production, or proliferation but rather on antigen-induced coexpression of CD25 and OX40 (CD134). Results Numbers of circulating gluten-specific Treg cells and effector T cells both increased significantly after oral wheat challenge, peaking at day 6. Surprisingly, we found that approximately 80% of the ex vivo circulating gluten-specific CD4+ T cells were FOXP3+CD39+ Treg cells, which reside within the pool of memory CD4+CD25+CD127lowCD45RO+ Treg cells. Although we observed normal suppressive function in peripheral polyclonal Treg cells from patients with celiac disease, after a short in vitro expansion, the gluten-specific FOXP3+CD39+ Treg cells exhibited significantly reduced suppressive function compared with polyclonal Treg cells. Conclusion This study provides the first estimation of FOXP3+CD39+ Treg cell frequency within circulating gluten-specific CD4+ T cells after oral gluten challenge of patients with celiac disease. FOXP3+CD39+ Treg cells comprised a major proportion of all circulating gluten-specific CD4+ T cells but had impaired suppressive function, indicating that Treg cell dysfunction might be a key contributor to disease pathogenesis

A Randomised Trial Comparing Genotypic and Virtual Phenotypic Interpretation of HIV Drug Resistance: The CREST Study

OBJECTIVES: The aim of this study was to compare the efficacy of different HIV drug resistance test reports (genotype and virtual phenotype) in patients who were changing their antiretroviral therapy (ART). DESIGN: Randomised, open-label trial with 48-week followup. SETTING: The study was conducted in a network of primary healthcare sites in Australia and New Zealand. PARTICIPANTS: Patients failing current ART with plasma HIV RNA > 2000 copies/mL who wished to change their current ART were eligible. Subjects were required to be > 18 years of age, previously treated with ART, have no intercurrent illnesses requiring active therapy, and to have provided written informed consent. INTERVENTIONS: Eligible subjects were randomly assigned to receive a genotype (group A) or genotype plus virtual phenotype (group B) prior to selection of their new antiretroviral regimen. OUTCOME MEASURES: Patient groups were compared for patterns of ART selection and surrogate outcomes (plasma viral load and CD4 counts) on an intention-to-treat basis over a 48-week period. RESULTS: Three hundred and twenty seven patients completing > one month of followup were included in these analyses. Resistance tests were the primary means by which ART regimens were selected (group A: 64%, group B: 62%; p = 0.32). At 48 weeks, there were no significant differences between the groups for mean change from baseline plasma HIV RNA (group A: 0.68 log copies/mL, group B: 0.58 log copies/mL; p = 0.23) and mean change from baseline CD4+ cell count (group A: 37 cells/mm(3), group B: 50 cells/mm(3); p = 0.28). CONCLUSIONS: In the absence of clear demonstrated benefits arising from the use of the virtual phenotype interpretation, this study suggests resistance testing using genotyping linked to a reliable interpretive algorithm is adequate for the management of HIV infection

SARS Coronavirus-2 microneutralisation and commercial serological assays correlated closely for some but not all enzyme immunoassays

Serological testing for SARS-CoV-2-specific antibodies provides important research and diagnostic information relating to COVID-19 prevalence, incidence and host immune response. A greater understanding of the relationship between functionally neutralising antibodies detected using microneutralisation assays and binding antibodies detected using scalable enzyme immunoassays (EIA) is needed in order to address protective immunity post-infection or vaccination, and assess EIA suitability as a surrogate test for screening of convalescent plasma donors. We assessed whether neutralising antibody titres correlated with signal cut-off ratios in five commercially available EIAs, and one in-house assay based on expressed spike protein targets. Sera from recovered patients or convalescent plasma donors who reported laboratory-confirmed SARS-CoV-2 infection (n = 200), and negative control sera collected prior to the COVID-19 pandemic (n = 100), were assessed in parallel. Performance was assessed by calculating EIA sensitivity and specificity with reference to microneutralisation. Neutralising antibodies were detected in 166 (83%) samples. Compared with this, the most sensitive EIAs were the Cobas Elecsys Anti-SARS-CoV-2 (98%) and Vitros Immunodiagnostic Anti-SARS-CoV-2 (100%), which detect total antibody targeting the N and S1 antigens, respectively. The assay with the best quantitative relationship with microneutralisation was the Euroimmun IgG. These results suggest the marker used (total Ab vs. IgG vs. IgA) and the target antigen are important determinants of assay performance. The strong correlation between microneutralisation and some commercially available assays demonstrates their potential for clinical and research use in assessing protection following infection or vaccination, and use as a surrogate test to assess donor suitability for convalescent plasma donation

Results of external quality assessment for proviral DNA testing of HIV tropism in the Maraviroc switch collaborative study

The Maraviroc Switch collaborative study (MARCH) is a study in aviremic patients on stable antiretroviral therapy and utilizes population-based sequencing of proviral DNA to determine HIV tropism and susceptibility to maraviroc. An external quality assessment (EQA) program was implemented to ensure competency in assessing the tropism of clinical samples conducted by MARCH laboratories (n = 14). The MARCH EQA has three prestudy phases assessing V3 loop sequencing and tropism determination using the bioinformatic algorithm geno2pheno, which generates a false-positive rate (FPR). DNA sequences with low FPRs are more likely to be from CXCR4-using (X4) viruses. Phase 1 of the EQA involved chromatogram interpretation. Phases 2, 2/3, and 3 involved patient and clonal samples. Clinical samples used in these phases were from treatment-experienced HIVinfected volunteers; 18/20 had viral loads o