Cytokine Registry Database of Stroke Patients (CRISP)

Purpose/Background: The aim of the study is to identify molecular biomarkers involve in patients who present with stroke and to determine their clinical usefulness as potential biomarkers in stroke patients as compared to patients without stroke. Materials & Methods: All patients presenting with ischemic stroke and hemorrhagic stroke at University of New Mexico Hospital (UNMH) will be screened for potential participation in this study based on following inclusion and exclusion criteria: Inclusion criteria: male/female of ages ≥ 18 years, patients whose standard stroke admission order sets are obtained for clinical care. Exclusion criteria: Patients \u3c18 year, with the history of prior stroke or any neurodegenerative or neuroinflammatory disease except multiple sclerosis (MS), pregnant women and prisoners. Cytokines will be measured in serum at two different time points: on admission and after 24 hours of admission. The biomarkers which will measured in serum will include interleukin (IL)-1, 4, 6, 10, 17, 23, 33, 36, 37, PDGF, VEGFM, TNF-a, ANNULIN, MMP-9, 12, NFk-B, MPO and glial factors; GMF, SI000-B and GM-6001. These biomarkers will be evaluated using enzyme linked immunosorbent assay (ELISA). Twenty-five percent of the total stroke patient serum samples will be matched by controls without ischemic or hemorrhagic stroke. The study was approved by UNM institutional review board (IRB). All sample and data collection is being done after patient or legally authorized individual sign the informed consent form. All the data is being collected on secured RedCAP database. Results: A total of 105 patients will be enrolled during the study period. Two sets of samples; one at baseline and the other after 24 hours of admission, will collected from each enrolled patient. At present, two patients are enrolled and their samples have been collected and stored per study protocol. The study is currently under recruitment phase and it is anticipated that the enrollment will be completed within next 2 months. Biomarker analysis will be done sequentially as patients will be enrolled per study protocol. Discussion/Conclusion: The CRISP study will give us understanding about the role of various cytokines and/or other biomarkers in the pathogenesis of formation of stroke. These biomarkers can potentially serve as identifiers in the clinical surveillance for acute stroke patients. The data from this study can be beneficial in the acute management of stroke patients

Multi‐frequency averaging (MFA) model of a generic electric vehicle powertrain suitable under variable frequency of averaging developed for remote operability

© The Institution of Engineering and Technology 2020. Geographically distributed hardware-in-the-loop (HIL) testing has the potential to allow hybrid vehicle powertrain components (battery, motor drive, and engine) to be developed at geographically remote locations but tested concurrently and coupled. Inter-location internet communication links can allow non-ideal behaviour observed in a physical component in one location (e.g. an electrical drive) to be imposed on another physical component elsewhere (e.g. an ICE), and vice-versa. A key challenge is how to represent the behaviour of a remote, physical component under testing in a local HIL environment. Internet communications are too slow and unreliable to transmit waveforms in real-time and so one solution is to use a local 'slave' model whose behaviour and parameters are tuned based on observations at the remote location. This study proposes a multifrequency averaging (MFA) slave model of an electric motor drive system for use in this application; it addresses a weakness in previously published work by extending the MFA model to variable frequency operation. The model was benchmarked against experimental operation (and its equivalent simulation model) in open-loop and closed-loop space vector pulse-width modulation control strategy, fixed and variable frequency operation. Results show significant reconciliation of model and experiment

Search for gravitational-lensing signatures in the full third observing run of the LIGO-Virgo network

Gravitational lensing by massive objects along the line of sight to the source causes distortions of gravitational wave-signals; such distortions may reveal information about fundamental physics, cosmology and astrophysics. In this work, we have extended the search for lensing signatures to all binary black hole events from the third observing run of the LIGO--Virgo network. We search for repeated signals from strong lensing by 1) performing targeted searches for subthreshold signals, 2) calculating the degree of overlap amongst the intrinsic parameters and sky location of pairs of signals, 3) comparing the similarities of the spectrograms amongst pairs of signals, and 4) performing dual-signal Bayesian analysis that takes into account selection effects and astrophysical knowledge. We also search for distortions to the gravitational waveform caused by 1) frequency-independent phase shifts in strongly lensed images, and 2) frequency-dependent modulation of the amplitude and phase due to point masses. None of these searches yields significant evidence for lensing. Finally, we use the non-detection of gravitational-wave lensing to constrain the lensing rate based on the latest merger-rate estimates and the fraction of dark matter composed of compact objects

Search for eccentric black hole coalescences during the third observing run of LIGO and Virgo

Despite the growing number of confident binary black hole coalescences observed through gravitational waves so far, the astrophysical origin of these binaries remains uncertain. Orbital eccentricity is one of the clearest tracers of binary formation channels. Identifying binary eccentricity, however, remains challenging due to the limited availability of gravitational waveforms that include effects of eccentricity. Here, we present observational results for a waveform-independent search sensitive to eccentric black hole coalescences, covering the third observing run (O3) of the LIGO and Virgo detectors. We identified no new high-significance candidates beyond those that were already identified with searches focusing on quasi-circular binaries. We determine the sensitivity of our search to high-mass (total mass M>70 M⊙) binaries covering eccentricities up to 0.3 at 15 Hz orbital frequency, and use this to compare model predictions to search results. Assuming all detections are indeed quasi-circular, for our fiducial population model, we place an upper limit for the merger rate density of high-mass binaries with eccentricities 0<e≤0.3 at 0.33 Gpc−3 yr−1 at 90\% confidence level

Ultralight vector dark matter search using data from the KAGRA O3GK run

Among the various candidates for dark matter (DM), ultralight vector DM can be probed by laser interferometric gravitational wave detectors through the measurement of oscillating length changes in the arm cavities. In this context, KAGRA has a unique feature due to differing compositions of its mirrors, enhancing the signal of vector DM in the length change in the auxiliary channels. Here we present the result of a search for U(1)B−L gauge boson DM using the KAGRA data from auxiliary length channels during the first joint observation run together with GEO600. By applying our search pipeline, which takes into account the stochastic nature of ultralight DM, upper bounds on the coupling strength between the U(1)B−L gauge boson and ordinary matter are obtained for a range of DM masses. While our constraints are less stringent than those derived from previous experiments, this study demonstrates the applicability of our method to the lower-mass vector DM search, which is made difficult in this measurement by the short observation time compared to the auto-correlation time scale of DM

Effect of Hypothyroidism on Different Forms of Actin in Rat Cerebral Neuronal Cultures Studied by an Improved DNase I Inhibition Assay

An improved DNase I inhibition assay for the filamentous actin (F-actin) and monomeric actin (G-actin) in brain cells has been developed. Unlike other methods, the cell lysis conditions and postlysis treatments, established by us, inhibited the temporal inactivation of actin in the cell lysate and maintained a stable F-actin/G-actin ratio for at least 4-5 h after lysis. The new procedure allowed separate quantitation of the noncytoskeletal F-actin in the Tritonsoluble fraction (12,000 g, 10 min supernatant) that did not readily sediment with the Triton-insoluble cytoskeletal Factin (12,000 g, 10 min pellet). We have applied this modified assay system to study the effect of hypothyroidism on different forms of actin using primary cultures of neurons derived from cerebra of neonatal normal and hypothyroid rats. Our results showed a 20% increase in the Triton-insoluble cytoskeletal F-actin in cultures from hypothyroid brain relative to normal controls. In the Triton-soluble fraction, containing the G-actin and the noncytoskeletal F-actin, cultures from hypothyroid brain showed a 15% increase in G-actin, whereas the F-actin remained unaltered. The 10% increase in total actin observed in this fraction from hypothyroid brain could be totally accounted for by the enhancement of G-actin. The mean F-actin/G-actin ratio in this fraction was about 30% higher in the cultures from normal brain compared to that of the hypothyroid system, which indicates that hypothyroidism tends to decrease the proportion of noncytoskeletal F-actin relative to G-actin

Thyroid Hormone-Induced Maturation of Astrocytes Is Associated with the Expression of New Variants of Vimentin and Their Phosphorylation

The role of thyroid hormone (TH)-induced vimentin expression in promoting the maturation of astrocytes has been investigated. Comparative immunocytochemical staining with vimentin antibody demonstrated distinctly different patterns of expression of vimentin during the progressive maturation of astrocytes of normal and TH-deficient astrocyte cultures. [35S]Methionine labeling of cells showed a significant decline in the level of vimentin in the hypothyroid cultures at all ages from day 5 to 20. Western blot analysis suggested that the maturation of normal astrocytes was associated with the appearance of several acidic and basic variants of vimentin, whose expression was significantly delayed or reduced in the TH-deficient astrocytes. In normal astrocyte cultures, two acidic variants of vimentin, one of similar molecular weight and the other of lower molecular weight, were found to be phosphorylated during the final transformation of the epithelioid form into the mature stellate form. None of these phosphorylated forms was evident in the TH-deficient astrocytes. This was further confirmed by negative immunocytochemical staining of 5- to 18-dayold cultures of TH-deficient astrocytes with antibody TM71, specific to phosphorylated vimentin, compared with age-matched normal astrocytes, which displayed consistent positive staining. The overall results indicate that TH-induced expression of phosphorylated forms of vimentin may be essential for the intracellular organization of the cytoskeleton in a way conducive to the morphological maturation of astrocytes. Key Words: Astrocytes— Morphology—Hypothyroidism—Vimentin— Variants—Phosphorylation

Role of Thyroid Hormone in the Morphological Differentiation and Maturation of Astrocytes: Temporal Correlation with Synthesis and Organization of Actin

Morphological changes and the molecular mechanisms associated with the maturation of astrocytes were studied under normal and thyroid hormone-deficient conditions using long-term (30 days) primary cultures derived from the neonatal rat brain. lmmunocytochemical staining of cells with a monoclonal antibody specific to glial fibrillary acidic protein demonstrated for the first time that, similar to their maturation in vivo, astrocytes maintained in normal serum-containing medium can undergo complete maturation involving two distinct stages of morphological differentiation (from radial glia to flat polygonal cells with epithelioid morphology and then to mature process-bearing cells with stellate morphology). Deficiency of thyroid hormone delays the first step and totally blocks the second stage of differentiation in the maturation process. Comparative staining of normal and thyroid hormone-deficient astrocytes with filamentous actin-specific fluorescein isothiocyanate-phalloidin and quantitation of the various forms of intracellular actin using an improved DNase I assay demonstrated that maturation of astroglial cells is associated with characteristic alterations in the level of cytoskeletal and non- cytoskeletal filamentous (F) actin. In particular, the maintenance of the epithelioid form of the hypothyroid astrocytes is associated with a progressive increase in the level of cytoskeletal F-actin and a concomitant decline in the level of non-cytoskeletal F-actin. Quantitation of actin mRNA by Northern blot analysis and studies on the rate of actin synthesis at various stages of differentiation showed that the initial transformation into the epithelioid form is associated with an increase in the rate of synthesis of actin and the expression of its mRNA, while the final transformation into the mature process-bearing form is correlated with a decline in these parameters. The results indicate that thyroid hormone plays an obligatory role in promoting the differentiation and maturation of astrocytes, and that during this process the hormone regulates the expression of actin and its intracellular organization in a way conducive to morphological differentiation