985 research outputs found
An optimal 9-point, finite-difference, frequency-space, 2-D scalar wave extrapolator
In this study, a new finite-difference technique is
designed to reduce the number of grid points needed in
frequency-space domain modeling. The new algorithm
uses optimal nine-point operators for the approximation
of the Laplacian and the mass acceleration terms. The
coefficients can be found by using the steepest descent
method so that the best normalized phase curves can be
obtained.
ABSTRACT
This method reduces the number of grid points per
wavelength to 4 or less, with consequent reductions of
computer memory and CPU time that are factors of tens
less than those involved in the conventional secondorder
approximation formula when a band type solver is
used on a scalar machine
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Activity of hippocampal adult-born neurons regulates alcohol withdrawal seizures.
Alcohol withdrawal (AW) after chronic alcohol exposure produces a series of symptoms, with AW-associated seizures being among the most serious and dangerous. However, the mechanism underlying AW seizures has yet to be established. In our mouse model, a sudden AW produced 2 waves of seizures: the first wave includes a surge of multiple seizures that occurs within hours to days of AW, and the second wave consists of sustained expression of epileptiform spikes and wave discharges (SWDs) during a protracted period of abstinence. We revealed that the structural and functional adaptations in newborn dentate granule cells (DGCs) in the hippocampus underlie the second wave of seizures but not the first wave. While the general morphology of newborn DGCs remained unchanged, AW increased the dendritic spine density of newborn DGCs, suggesting that AW induced synaptic connectivity of newborn DGCs with excitatory afferent neurons and enhanced excitability of newborn DGCs. Indeed, specific activation and suppression of newborn DGCs by the chemogenetic DREADD method increased and decreased the expression of epileptiform SWDs, respectively, during abstinence. Thus, our study unveiled that the pathological plasticity of hippocampal newborn DGCs underlies AW seizures during a protracted period of abstinence, providing critical insight into hippocampal neural circuits as a foundation to understand and treat AW seizures
Antibiotic resistance mechanisms inform discovery: identification and characterization of a novel amycolatopsis strain producing ristocetin.
Discovering new antibiotics is a major scientific challenge, made increasingly urgent by the continued development of resistance in bacterial pathogens. A fundamental understanding of the mechanisms of bacterial antibiotic resistance will be vital for the future discovery or design of new, more effective antibiotics. We have exploited our intimate knowledge of the molecular mechanism of glycopeptide antibiotic resistance in the harmless bacterium Streptomyces coelicolor to develop a new two-step cell wall bioactivity screen, which efficiently identified a new actinomycete strain containing a previously uncharacterized glycopeptide biosynthetic gene cluster. The screen first identifies natural product extracts capable of triggering a generalized cell wall stress response and then specifically selects for glycopeptide antibacterials by assaying for the induction of glycopeptide resistance genes. In this study, we established a diverse natural product extract library from actinomycete strains isolated from locations with widely varying climates and ecologies, and we screened them using the novel two-step bioassay system. The bioassay ultimately identified a single strain harboring the previously unidentified biosynthetic gene cluster for the glycopeptide ristocetin, providing a proof of principle for the effectiveness of the screen. This is the first report of the ristocetin biosynthetic gene cluster, which is predicted to include some interesting and previously uncharacterized enzymes. By focusing on screening libraries of microbial extracts, this strategy provides the certainty that identified producer strains are competent for growth and biosynthesis of the detected glycopeptide under laboratory conditions.This work was supported by funding from the Royal Society, UK (516002.K5877/ROG), the Medical Research council, UK (G0700141) and St. Johnās College, University of CambridgeThis the the author accepted manuscript. The final version is available from ASM at http://aac.asm.org/content/early/2014/07/09/AAC.03349-14.abstract
Rudder Gap Flow Control for Cavitation Suppression
For the suppression of rudder cavitation, especially within and around the gap between the stationary and movable parts, flow control devices were developed. In the present study, both experimental and computational analyses of the flow control devices were carried out. The new rudder system is equipped with cam devices, which effectively close the gap between the stationary horn/pintle and movable flaps. Model scale experiments of surface pressure measurements, flow field visualization near the gap using PIV, and cavitation behavior observation were conducted in a cavitation tunnel. The experiments were simulated using a computational fluid dynamics tool and the results are compared for validation. It is confirmed that the flow control devices effectively suppresses the rudder gap cavitation and, at the same time, augments lifthttp://deepblue.lib.umich.edu/bitstream/2027.42/84266/1/CAV2009-final70.pd
Longitudinal assessment of urinary ALCAM, HPX, and PRDX6 in Korean patients with systemic lupus erythematosus: implications for disease activity monitoring and treatment response
IntroductionThis study aimed to demonstrate the potential of activated leukocyte cell adhesion molecule (ALCAM), hemopexin (HPX), and peroxiredoxin 6 (PRDX6) as urine biomarkers for systemic lupus erythematosus (SLE).MethodsUrine samples were collected from 138 Korean patients with SLE from the Ajou Lupus Cohort and 39 healthy controls (HC). The concentrations of urine biomarkers were analyzed using enzyme-linked immunosorbent assay kits specific for ALCAM, HPX, and PRDX6, respectively. Receiver operating characteristic (ROC) curve analysis was performed to evaluate the diagnostic utility, and Pearsonās correlation analysis was conducted to assess the relationships between the disease activity and urine biomarkers.ResultsPatients with SLE and patients with lupus nephritis (LN) showed significantly elevated ALCAM, HPX, and PRDX6 levels compared with HCs. ALCAM, HPX, and PRDX6 showed significant diagnostic values, especially for lupus nephritis (LN), with areas under the receiver operating characteristic curve for LN was 0.850 for ALCAM (95% CI, 0.778ā0.921), 0.781 for HPX (95% CI, 0.695ā0.867), and 0.714 for PRDX6 (95% CI, 0.617ā0.812). Correlation analysis revealed that all proteins were significantly associated with anti-double stranded DNA antibody (ALCAM, r = 0.350, p < 0.001; HPX, r = 0.346, p < 0.001; PRDX6, r = 0.191, p = 0.026) and SLEDAI (ALCAM, r = 0.526, p < 0.001; HPX, r = 0.479, p < 0.001; PRDX6, r = 0.262, p = 0.002). Results from the follow-up of the three biomarker levels in these patients revealed a significant decrease, showing a positive correlation with changes in SLEDAI-2k scores (ALCAM, r = 0.502, p < 0.001; HPX, r = 0.475, p < 0.001; PRDX6, r = 0.245, p = 0.026), indicating their potential as indicators for tracking disease activity.DiscussionsUrinary ALCAM, HPX, and PRDX6 levels have diagnostic value and reflect disease activity in Korean patients with SLE, emphasizing their potential for non-invasive monitoring and treatment response evaluation
Abnormalities of Rest-Activity and Light Exposure Rhythms Associated with Cognitive Function in Patients with Mild Cognitive Impairment (MCI)
We aimed to examine the difference in rest-activity rhythm (RAR) and light exposure rhythm (LER) between patients with mild cognitive impairment (MCI) and normal controls (NC), and to verify their relationships with cognitive functions. The neuropsychological battery was administered to participants above 50 years old. The MCI diagnosis was made according to Petersenās criteria. Ten patients with MCI (77.90 Ā± 6.95 years) and eight NC (74.75 Ā± 5.06 years) were studied. Actigraphy (Actiwatch 2; Philips Respironics) was recorded at home for 5 days. RAR and LER variables, including interdaily stability (IS), intradaily variability (IV) and relative amplitude, were calculated using nonparametric analyses. The associations between cognitive performance and RAR and LER variables were explored using generalized linear models. There were no significant differences in RAR or LER variables between MCI and NC. There was a significant main effect of RAR-IS on the Stroop Color and Word Test (SCWT), indicating a positive relationship between RAR stability and SCWT performance. There was a significant group by RAR-IS interaction on Trail Making Test-A, indicating a negative relationship in MCI compared to NC. There was a significant group by LER-IV interaction on the Boston Naming Test, indicating a positive relationship in MCI compared to NC. There was no disruption in RAR and LER in patients with MCI. Our study showed that circadian rhythm abnormality was associated with a decline in executive function. However, circadian rhythm abnormality was not associated with declines in processing speed and language function in patients with MCI, implying an altered pathophysiology compared to NC
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