2,708 research outputs found
Combined Structural Optimization and Aeroelastic Analysis of a Vertical Axis Wind Turbine
Floating offshore wind energy poses challenges on the turbine design. A possible solution is vertical axis wind turbines, which are possibly easier to scale-up and require less components (lower maintenance) and a smaller floating structure than horizontal axis wind turbines. This paper presents a structural optimization and aeroelastic analysis of an optimized Troposkein vertical axis wind turbine to minimize the relation between the rotor mass and the swept area. The aeroelastic behavior of the different designs has been analyzed using a modified version of the HAWC2 code with the Actuator Cylinder model to compute the aerodynamics of the vertical axis wind turbine. The combined shape and topology optimization of a vertical axis wind turbine show a minimum mass to area ratio of 1.82 kg/m2 for blades with varying blade sections from a NACA 0040 at the attachment points to a NACA 0015 in the equatorial region. During an aeroelastic analysis of the wind turbine a maximum flapwise deflection of 0.45 m and a maximum edgewise deflection of 0.47 m were found. While the turbine is aeroelastically stable, an oscillation as a result of resonance reduces the fatigue life
Single-cell multi-omics analysis reveals IFN-driven alterations in T lymphocytes and natural killer cells in systemic lupus erythematosus
Background: The characterisation of the peripheral immune system in the autoimmune disease systemic lupus erythematosus (SLE) at the single-cell level has been limited by the reduced sensitivity of current whole-transcriptomic technologies. Here we employ a targeted single-cell multi-omics approach, combining protein and mRNA quantification, to generate a high-resolution map of the T lymphocyte and natural killer (NK) cell populations in blood from SLE patients.
Methods: We designed a custom panel to quantify the transcription of 534 genes in parallel with the expression of 51 surface protein targets using the BD Rhapsody AbSeq single-cell system. We applied this technology to profile 20,656 T and NK cells isolated from peripheral blood from an SLE patient with a type I interferon (IFN)-induced gene expression signature (IFNhi), and an age- and sex- matched IFNlow SLE patient and healthy donor.
Results: We confirmed the presence of a rare cytotoxic CD4+ T cell (CTL) subset, which was exclusively present in the IFNhi patient. Furthermore, we identified additional alterations consistent with increased immune activation in this patient, most notably a shift towards terminally differentiated CD57+ CD8+ T cell and CD16+ NKdim phenotypes, and the presence of a subset of recently-activated naïve CD4+ T cells.
Conclusions: Our results identify IFN-driven changes in the composition and phenotype of T and NK cells that are consistent with a systemic immune activation within the IFNhi patient, and underscore the added resolving power of this multi-omics approach to identify rare immune subsets. Consequently, we were able to find evidence for novel cellular peripheral biomarkers of SLE disease activity, including a subpopulation of CD57+ CD4+ CTLs
Stain Consistency Learning: Handling Stain Variation for Automatic Digital Pathology Segmentation
Stain variation is a unique challenge associated with automated analysis of
digital pathology. Numerous methods have been developed to improve the
robustness of machine learning methods to stain variation, but comparative
studies have demonstrated limited benefits to performance. Moreover, methods to
handle stain variation were largely developed for H&E stained data, with
evaluation generally limited to classification tasks. Here we propose Stain
Consistency Learning, a novel framework combining stain-specific augmentation
with a stain consistency loss function to learn stain colour invariant
features. We perform the first, extensive comparison of methods to handle stain
variation for segmentation tasks, comparing ten methods on Masson's trichrome
and H&E stained cell and nuclei datasets, respectively. We observed that stain
normalisation methods resulted in equivalent or worse performance, while stain
augmentation or stain adversarial methods demonstrated improved performance,
with the best performance consistently achieved by our proposed approach. The
code is available at: https://github.com/mlyg/stain_consistency_learnin
A dynamical framework for the origin of the diagonal South Pacific and South Atlantic convergence zones
The South Pacific Convergence Zone (SPCZ) and South Atlantic Convergence Zone (SACZ) are diagonal bands of precipitation that extend from the equator southeastward into the Southern Hemisphere over the western Pacific and Atlantic Oceans, respectively. With mean precipitation rates over 5 mm day−1, they are a major component of the tropical and global climate in austral summer. However, their basic formation mechanism is not fully understood. Here, a conceptual framework for the diagonal convergence zones is developed, based on calculations of the vorticity budget from reanalysis and Rossby wave theory. Wave trains propagate eastward along the Southern Hemisphere subtropical jet, with initially quasi-circular vorticity centres. In the zonally sheared environment on the equatorward flank of the jet, these vorticity centres become elongated and develop a northwest-southeast tilt. Ray tracing diagnostics in a non-divergent, barotropic Rossby wave framework then explain the observed equatorward propagation of these diagonal vorticity structures toward the westerly ducts over the equatorial Pacific and Atlantic. The baroclinic component of these circulations leads to destabilisation and ascent ahead of the cyclonic vorticity anomaly in the wave, triggering deep convection because of the high sea surface temperatures in this region. Latent heat release then forces additional ascent and strong upper-tropospheric divergence, with an associated anticyclonic vorticity tendency. A vorticity budget shows that this cancels out the advective cyclonic vorticity tendency in the wave train over the SPCZ, and dissipates the wave within a day. The mean SPCZ is consequently comprised of the sum of these pulses of diagonal bands of precipitation. Similar mechanisms also operate in the SACZ. However, the vorticity anomalies in the wave trains are stronger, and the precipitation and negative feedback from the divergence and anticyclonic vorticity tendency are weaker, resulting in continued propagation of the wave and a more diffuse diagonal convergence zone
CD56bright natural killer cells preferentially kill proliferating CD4+ T cells
Human CD56br natural killer (NK) cells represent a small subset of CD56+ NK cells in circulation and are largely tissue-resident. The frequency and number of CD56br NK cells in blood has been shown to increase following administration of low-dose IL-2 (LD-IL2), a therapy aimed to specifically expand CD4+ regulatory T cells (Tregs). Given the potential clinical application of LD-IL-2 immunotherapy across several immune diseases, including the autoimmune disease type 1 diabetes, a better understanding of the functional consequences of this expansion is urgently needed. In this study, we developed an in vitro co-culture assay with activated CD4+ T cells to measure NK cell killing efficiency. We show that CD56br and CD56dim NK cells show similar efficiency at killing activated CD4+ conventional T (Tconv) and Treg cell subsets. However, in contrast to CD56dim cells, CD56br NK cells preferentially target highly proliferative cells. We hypothesize that CD56br NK cells have an immunoregulatory role through the elimination of proliferating autoreactive CD4+ Tconv cells that have escaped Treg suppression. These results have implications for the interpretation of current and future trials of LD-IL-2 by providing evidence for a new, possibly beneficial immunomodulatory mechanism of LD-IL-2-expanded CD56br NK cells
Two-Stage, 90-GHz, Low-Noise Amplifier
A device has been developed for coherent detection of the polarization of the cosmic microwave background (CMB). A two-stage amplifier has been designed that covers 75-110 GHz. The device uses the emerging 35-nm InP HEMT technology recently developed at Northrop Grumman Corporation primarily for use at higher frequencies. The amplifier has more than 18 dB gain and less than 35 K noise figure across the band. These devices have noise less than 30 K at 100 GHz. The development started with design activities at JPL, as well as characterization of multichip modules using existing InP. Following processing, a test campaign was carried out using single-chip modules at 100 GHz. Successful development of the chips will lead to development of multichip modules, with simultaneous Q and U Stokes parameter detection. This MMIC (monolithic microwave integrated circuit) amplifier takes advantage of performance improvements intended for higher frequencies, but in this innovation are applied at 90 GHz. The large amount of available gain ultimately leads to lower possible noise performance at 90 GHz
The cellular and synaptic architecture of the mechanosensory dorsal horn
The deep dorsal horn is a poorly characterized spinal cord region implicated in processing low-threshold mechanoreceptor (LTMR) information. We report an array of mouse genetic tools for defining neuronal components and functions of the dorsal horn LTMR-recipient zone (LTMR-RZ), a role for LTMR-RZ processing in tactile perception, and the basic logic of LTMR-RZ organization. We found an unexpectedly high degree of neuronal diversity in the LTMR-RZ: seven excitatory and four inhibitory subtypes of interneurons exhibiting unique morphological, physiological, and synaptic properties. Remarkably, LTMRs form synapses on between four and 11 LTMR-RZ interneuron subtypes, while each LTMR-RZ interneuron subtype samples inputs from at least one to three LTMR classes, as well as spinal cord interneurons and corticospinal neurons. Thus, the LTMR-RZ is a somatosensory processing region endowed with a neuronal complexity that rivals the retina and functions to pattern the activity of ascending touch pathways that underlie tactile perception
Multi-parametric flow cytometric and genetic investigation of the peripheral B cell compartment in human type 1 diabetes.
The appearance of circulating islet-specific autoantibodies before disease diagnosis is a hallmark of human type 1 diabetes (T1D), and suggests a role for B cells in the pathogenesis of the disease. Alterations in the peripheral B cell compartment have been reported in T1D patients; however, to date, such studies have produced conflicting results and have been limited by sample size. In this study, we have performed a detailed characterization of the B cell compartment in T1D patients (n = 45) and healthy controls (n = 46), and assessed the secretion of the anti-inflammatory cytokine interleukin (IL)-10 in purified B cells from the same donors. Overall, we found no evidence for a profound alteration of the B cell compartment or in the production of IL-10 in peripheral blood of T1D patients. We also investigated age-related changes in peripheral B cell subsets and confirmed the sharp decrease with age of transitional CD19(+) CD27(-) CD24(hi) CD38(hi) B cells, a subset that has recently been ascribed a putative regulatory function. Genetic analysis of the B cell compartment revealed evidence for association of the IL2-IL21 T1D locus with IL-10 production by both memory B cells (P = 6·4 × 10(-4) ) and islet-specific CD4(+) T cells (P = 2·9 × 10(-3) ). In contrast to previous reports, we found no evidence for an alteration of the B cell compartment in healthy individuals homozygous for the non-synonymous PTPN22 Trp(620) T1D risk allele (rs2476601; Arg(620) Trp). The IL2-IL21 association we have identified, if confirmed, suggests a novel role for B cells in T1D pathogenesis through the production of IL-10, and reinforces the importance of IL-10 production by autoreactive CD4(+) T cells
Role of a Ubiquitously Expressed Receptor in the Vertebrate Olfactory System
Odorant cues are recognized by receptors expressed on olfactory sensory neurons, the primary sensory neurons of the olfactory epithelium. Odorant receptors typically obey the “one receptor, one neuron” rule, in which the receptive field of the olfactory neuron is determined by the singular odorant receptor that it expresses. Odor-evoked receptor activity across the population of olfactory neurons is then interpreted by the brain to identify the molecular nature of the odorant stimulus. In the present study, we characterized the properties of a C family G-protein-coupled receptor that, unlike most other odorant receptors, is expressed in a large population of microvillous sensory neurons in the zebrafish olfactory epithelium and the mouse vomeronasal organ. We found that this receptor, OlfCc1 in zebrafish and its murine ortholog Vmn2r1, is a calcium-dependent, low-sensitivity receptor specific for the hydrophobic amino acids isoleucine, leucine, and valine. Loss-of-function experiments in zebrafish embryos demonstrate that OlfCc1 is required for olfactory responses to a diverse mixture of polar, nonpolar, acidic, and basic amino acids. OlfCc1 was also found to promote localization of other OlfC receptor family members to the plasma membrane in heterologous cells. Together, these results suggest that the broadly expressed OlfCc1 is required for amino acid detection by the olfactory system and suggest that it plays a role in the function and/or intracellular trafficking of other olfactory and vomeronasal receptors with which it is coexpressed
The distribution of estuarine fish larvae: nutritional condition and co-occurrence with predators and prey
Fish larvae were collected monthly between March and September 1997 in the Mira and Guadiana estuaries (southern Portugal). Hydrological parameters were registered and zooplankton samples were obtained simultaneously. Densities of fish larvae (ind.100 m(-3)) were calculated from 211 samples and larval nutritional condition measured as RNA/DNA ratios were obtained for 346 individuals, using a fluorimetric method for nucleic acid quantification. Correlating variables were further studied using multiple regression analysis in order to assess the relative importance of abiotic and biotic factors affecting within-year trends in abundance and nutritional condition of estuarine fish larvae. Results indicated that: 1) the abundance of fish larvae seems conditioned by temperature and predation; and 2) their nutritional condition is dependent on temperature and prey availability. Temperature is an important variable structuring estuaries and therefore conditions the behaviour and physiology of fish larvae. Furthermore, the co-occurrence of predators and larvae might be related to similar feeding patterns or comensalism. Whenever feeding conditions are suitable, they usually determine enhanced growth and nutritional condition. However, predation seems to control this latter relationship through its effect on larval mortality. (C) 2000 Editions scientifiques et Medicales Elsevier SAS.info:eu-repo/semantics/publishedVersio
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