2,065 research outputs found

    Liquefaction Analysis of Lower San Fernando Darn Using Strength Ratios

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    Olson (2000) evaluated 33 liquefaction flow failure case histories to assess the yield strength ratio and liquefied strength ratio mobilized during the failures. Using back-analysis procedures developed by Olson (2000), yield and liquefied shear strengths are shown to be proportional to the pre-failure vertical effective stress and are related to standard and cone penetration resistances. This paper examines the triggering of liquefaction and subsequent flow failure of Lower San Fernando Dam using yield and liquefied strength ratios. The yield strength ratio is used to correctly predict the occurrence of liquefaction in the upstream hydraulic fill of the dam, and the liquefied shear strength ratio is used to correctly predict the subsequent flow failure of the upstream slope. The relationships for the yield and liquefied ratios are presented, and their application to existing or new structures is illustrated using the Lower San Fernando Dam case history

    Dexmedetomidine Alters the Inflammatory Profile of Rat Microglia In Vitro

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    BACKGROUND: Microglia are a primary mediator of the neuroinflammatory response to neurologic injury, such as that in traumatic brain injury. Their response includes changes to their cytokine expression, metabolic profile, and immunophenotype. Dexmedetomidine (DEX) is an α METHODS: Primary microglia were isolated from Sprague-Dawley rats and cultured. Microglia were activated using multiple mediators: lipopolysaccharide (LPS), polyinosinic-polycytidylic acid (Poly I:C), and traumatic brain injury damage-associated molecular patterns (DAMP) from a rat that sustained a prior controlled cortical impact injury. After activation, cultures were treated with DEX. At the 24-h interval, the cell supernatant and cells were collected for the following studies: cytokine expression (tumor necrosis factor-α [TNFα], interleukin-10 [IL-10]) via enzyme-linked immunosorbent assay, 6-phosphofructokinase enzyme activity assay, and immunophenotype profiling with flow cytometry. Cytokine expression and metabolic enzyme activity data were analyzed using two-way analysis of variance. Cell surface marker expression was analyzed using FlowJo software. RESULTS: In LPS-treated cultures, DEX treatment decreased the expression of TNFα from microglia (mean difference = 121.5 ± 15.96 pg/mL; p \u3c 0.0001). Overall, DEX-treated cultures had a lower expression of IL-10 than nontreated cultures (mean difference = 39.33 ± 14.50 pg/mL, p \u3c 0.0001). DEX decreased IL-10 expression in LPS-stimulated microglia (mean difference = 74.93 ± 12.50 pg/mL, p = 0.0039) and Poly I:C-stimulated microglia (mean difference = 23.27 ± 6.405 pg/mL, p = 0.0221). In DAMP-stimulated microglia, DEX decreased the activity of 6-phosphofructokinase (mean difference = 18.79 ± 6.508 units/mL; p = 0.0421). The microglial immunophenotype was altered to varying degrees with different inflammatory stimuli and DEX treatment. CONCLUSIONS: DEX may alter the neuroinflammatory response of microglia. By altering the microglial profile, DEX may affect the progression of neurologic injury

    A Decade of Blood-Brain Barrier Permeability Assays: Revisiting Old Traumatic Brain Injury Rat Data for New Insights and Experimental Design

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    Increased microvascular permeability at the level of the blood-brain barrier (BBB) often leads to vasogenic brain edema following traumatic brain injury (TBI). These pathologic conditions compromise the integrity of the neurovascular unit resulting in severe brain dysfunction. To quantify this permeability and assess ionic equillibrium, preclinical researchers have relied on the use of various molecular weight permeable dyes such as Evans Blue that normally cannot enter the brain parenchyma under homeostatic conditions. Evans Blue, the most cited of the molecular weight dyes, has reported reproducibility issues because of harsh extraction processes, suboptimal detection via absorbance, and wide excitation fluorescence spectra associated with the dye. Our laboratory group transitioned to Alexa Fluor 680, a far-red dye with improved sensitivity compared to Evans Blue and thus improved reproducibility to alleviate this issue. To evaluate our reproducibility and increase the rigor of our experimental design, we retrospectively analyzed our controlled cortical impact (CCI) experiments over the past 10 years to evaluate effect size with larger samples and potential sources of variability. All of our BBB permeability experiments were performed with Male, Sprague Dawley rats weighing between 225–300 grams. Historically, Sprague Dawleys were randomly divided into treatment groups: SHAM, CCI, and a stem cell-based treatment from years 2007–2020. The assessment of microvascular hyperpermeability were evaluated by comparing the mean at minimum threshold, area at 1k-2k, and intensity density obtained from Alexa Fluor 680 permeability data. Studies utilizing Evans Blue were further compared by tip depth, diameter size, and the hemisphere of injury. Statistical evaluation utilizing the G Power software analysis did not yield a significant difference in sample size comparing experimental groups for Evans Blue and Alexa Fluor 680 analyzed brain tissue. Our analysis also demonstrated a trend in that recent studies (years 2018–2020) have yielded more compact sample sizes between experimental groups in Alexa Fluor 680 analyzed rats. This retrospective study further revealed that Alexa Fluor 680 image analysis provides greater sensitivity to BBB permeability following TBI in comparison to Evans Blue. Significant differences in sample size were not detected between Evans Blue and Alexa Fluor 680; there were significant differences found throughout year to year analysis at the lower range of thresholds

    Academic Budget Prioritization in a Shared Governance University

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    Academic program review and budget prioritization in a shared governance environment with transparency and results was critical for Minnesota State University-Mankato, in preparation for forecasted budget reductions. Using an interactive format, this session will review the development of program evaluation metrics, highlight the process and timeline used, present key lessons learned, and provide attendees an opportunity to consider application on their home campus

    Operation of rain gauge and ground-water monitoring networks for the Imperial Valley Water Authority, year six: September 1997 - August 1998

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    The Illinois State Water Survey (ISWS), under contract to the Imperial Valley Water Authority (IVWA), has operated a network of rain gauges in Mason and Tazewell Counties since August 1992. The ISWS also established a network of ground-water observation wells in the Mason-Tazewell area. The networks are located in the most heavily irrigated region of the state. Ground water in various aquifers are the major source of the irrigation and domestic water supplies in the region. Recent extreme weather events (e.g., the drought of 1988 and the great flood of 1993) resulted in large fluctuations of the ground-water levels in the Imperial Valley area. The purpose of the rain gauge network and the ground-water observation well network is to collect a long-term series of data to determine the rate of ground-water drawdown in dry periods and during the growing season, and the rate at which the aquifers recharge. Precipitation is recorded for each storm that traverses the Imperial Valley, and ground-water levels at the 13 observation wells are measured the first of each month. The database from these networks consists of 6 years of precipitation data and 4 years of ground-water observations. At the beginning of the ground-water observations in 1995, the water levels were at the highest in the four years of observation. These high ground-water levels were the result of the very wet 1992-1995 period when annual precipitation was above the 30-year normals at both Havana and Mason City. From September 1995-August 1997 precipitation in the region was below the 30-year normal. The 1997-1998 observation year had rainfall above the 30-year normal. Ground-water levels in the observation wells mirrored these rainfall patterns, showing a general downward trend during the dry years and a recovery in the wet 1997-1998 year. Seasonal increases in the ground-water levels were observed at most wells during the late spring and early summer, followed by decreases in August-November ground water levels. Analysis indicates that the ground-water levels are affected by both the precipitation in the Imperial Valley area and the Illinois River stages. The observation wells closest to the Illinois River show an increase in water levels whenever the river stage is high. Generally, the water levels in the wells correlate best with precipitation and Illinois River stages one to two months before the water levels are measured, i.e., the June ground-water levels are most highly correlated with the Illinois River stage or precipitation that occurs in either April or May. The analyses conducted indicate the need for continued operation of both networks due to inconsistencies associated with ground-water levels, precipitation, and the Illinois River stage. For instance, the Mason-Tazwell observation well number 2 (MTOW-2) is located near the center of Mason County well away from the Illinois River, but it has an equal correlation with the Illinois River stage and the precipitation in the area. Additional analysis needs to be undertaken to explain this unusual finding

    Enhancing Mesenchymal Stromal Cell Potency: Inflammatory Licensing via Mechanotransduction

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    Mesenchymal stromal cells (MSC) undergo functional maturation upon their migration from bone marrow and introduction to a site of injury. This inflammatory licensing leads to heightened immune regulation via cell-to-cell interaction and the secretion of immunomodulatory molecules, such as anti-inflammatory mediators and antioxidants. Pro-inflammatory cytokines are a recognized catalyst of inflammatory licensing; however, biomechanical forces, such as fluid shear stress, are a second, distinct class of stimuli that incite functional maturation. Here we show mechanotransduction, achieved by exposing MSC to various grades of wall shear stress (WSS) within a scalable conditioning platform, enhances the immunomodulatory potential of MSC independent of classical pro-inflammatory cytokines. A dose-dependent effect of WSS on potency is evidenced by production of prostaglandin E2 (PGE2) and indoleamine 2,3 dioxygenase 1 (IDO1), as well as suppression of tumor necrosis factor-α (TNF- α) and interferon-γ (IFN-γ) production by activated immune cells. Consistent, reproducible licensing is demonstrated in adipose tissue and bone marrow human derived MSC without significant impact on cell viability, cellular yield, or identity. Transcriptome analysis of WSS-conditioned BM-MSC elucidates the broader phenotypic implications on the differential expression of immunomodulatory factors. These results suggest mechanotransduction as a viable, scalable pre-conditioning alternative to pro-inflammatory cytokines. Enhancing the immunomodulatory capacity of MSC via biomechanical conditioning represents a novel cell therapy manufacturing approach

    Hyperspectral Data Processing Improves PpIX Contrast During Fluorescence Guided Surgery of Human Brain Tumors.

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    Fluorescence guided surgery (FGS) using aminolevulinic-acid (ALA) induced protoporphyrin IX (PpIX) provides intraoperative visual contrast between normal and malignant tissue during resection of high grade gliomas. However, maps of the PpIX biodistribution within the surgical field based on either visual perception or the raw fluorescence emissions can be masked by background signals or distorted by variations in tissue optical properties. This study evaluates the impact of algorithmic processing of hyperspectral imaging acquisitions on the sensitivity and contrast of PpIX maps. Measurements in tissue-simulating phantoms showed that (I) spectral fitting enhanced PpIX sensitivity compared with visible or integrated fluorescence, (II) confidence-filtering automatically determined the lower limit of detection based on the strength of the PpIX spectral signature in the collected emission spectrum (0.014–0.041 μg/ml in phantoms), and (III) optical-property corrected PpIX estimates were more highly correlated with independent probe measurements (r = 0.98) than with spectral fitting alone (r = 0.91) or integrated fluorescence (r = 0.82). Application to in vivo case examples from clinical neurosurgeries revealed changes to the localization and contrast of PpIX maps, making concentrations accessible that were not visually apparent. Adoption of these methods has the potential to maintain sensitive and accurate visualization of PpIX contrast over the course of surgery

    Degenerate dispersive equations arising in the study of magma dynamics

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    An outstanding problem in Earth science is understanding the method of transport of magma in the Earth's mantle. Models for this process, transport in a viscously deformable porous media, give rise to scalar degenerate, dispersive, nonlinear wave equations. We establish a general local well-posedness for a physical class of data (roughly H1H^1) via fixed point methods. The strategy requires positive lower bounds on the solution. This is extended to global existence for a subset of possible nonlinearities by making use of certain conservation laws associated with the equations. Furthermore, we construct a Lyapunov energy functional, which is locally convex about the uniform state, and prove (global in time) nonlinear dynamic stability of the uniform state for any choice of nonlinearity. We compare the dynamics to that of other problems and discuss open questions concerning a larger range of nonlinearities, for which we conjecture global existence.Comment: 27 Pages, 7 figures are not present in this version. See http://www.columbia.edu/~grs2103/ for a PDF with figures. Submitted to Nonlinearit

    Peripheral Blood Monocytes as a Therapeutic Target for Marrow Stromal Cells in Stroke Patients

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    BACKGROUND: Systemic administration of marrow stromal cells METHODS: Peripheral blood from stroke patients was collected at 5-7 days ( RESULTS: Our results show that there is a higher release of IFN-γ and IL-10 from monocytes isolated from peripheral blood at day 5-7 after stroke compared with monocytes from healthy controls. In trans-well co-cultures of MSCs and monocytes isolated from stroke patients, we found statistically significant increased levels of IL-4 and MCP-1, and decreased levels of IL-6, IL-1β, and TNF-α. Addition of MSCs to monocytes increased the secretions of Fractalkine, IL-6, and MCP-1, while the secretions of TNF-α decreased, as compared to the secretions from monocytes alone. When MSCs were added to monocytes from stroke patients, they decreased the levels of IL-1β, and increased the levels of IL-10 significantly more as compared to when they were added to monocytes from control patients. CONCLUSION: The systemic circulation of stroke patients may differentially interact with MSCs to release soluble factors integral to their paracrine mechanisms of benefit. Our study finds that the effect of MSCs on Mϕ is different on those derived from stroke patients blood as compared to healthy controls. These findings suggest immunomodulation of peripheral immune cells as a therapeutic target for MSCs in patients with acute stroke
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