99 research outputs found
LTB formation in porcine neutrophils was unaffected by RCM-101 (1, 10 and 100 μg ml)
No full text<p><b>Copyright information:</b></p><p>Taken from "Inhibition of Release of Vasoactive and Inflammatory Mediators in Airway and Vascular Tissues and Macrophages By a Chinese Herbal Medicine Formula for Allergic Rhinitis"</p><p></p><p>Evidence-based Complementary and Alternative Medicine 2006;4(2):209-217.</p><p>Published online 27 Nov 2006</p><p>PMCID:PMC1876611.</p><p>© 2006 The Author(s).</p> Nordihydroguaiaretic acid (NDGA; 0.1, 1 and 10 μg ml) produced concentration-dependent inhibition of LTB formation. Data plotted are means ± SEM ( = 8 in each case). < 0.05, one-way ANOVA and Dunnet's test
Stiffness reduction of cantilever I-beams through lateral torsional buckling for compliant beams
No full textLateral torsional buckling (LTB) of I-beams is an established buckling phenomenon in civil and structural engineering known for causing structural failures. However when a buckling instability is present the structure contains a form of negative stiffness. Due to the observed tendency of I-beams subject to LTB to twist about their longitudinal axis it is suspected that such I-beams contain a form of negative rotational stiffness about their longitudinal axis. Rather than considering LTB as a failure mode for structures, this work aims to investigate the potential of cantilever I-beams subject to LTB having a reduced rotational stiffness about their longitudinal axis with minimal lateral deflection on demand by subjecting the beam to LTB. By minimising the lateral deflection the longitudinal twisting behaviour approaches the behaviour of a compliant rotational joint. The occurrence of negative rotational stiffness in the buckled state is verified and a parameter study is executed to evaluate the stiffness reduction and co-occurring lateral deflection by means of 1-dimensional finite element modelling. Finally an optimisation is performed to obtain a beam with minimal lateral deflection and a significant reduction in longitudinal rotational stiffness. The simulated behaviour is experimentally validated. The simulation and experiment showed that rotational stiffness can be significantly reduced through LTB. Additionally the experiment verified the significant reduction of lateral deflection for the optimised beam. Overall this work forms an initial step towards the use of reduced rotational stiffness of beams by exploiting lateral torsional buckling.Mechanical Engineerin
Adjuvant-Mediated Epitope Specificity and Enhanced Neutralizing Activity of Antibodies Targeting Dengue Virus Envelope Protein
No full textabstract: The heat-labile toxins (LT) produced by enterotoxigenic Escherichia coli display adjuvant effects to coadministered antigens, leading to enhanced production of serum antibodies. Despite extensive knowledge of the adjuvant properties of LT derivatives, including in vitro-generated non-toxic mutant forms, little is known about the capacity of these adjuvants to modulate the epitope specificity of antibodies directed against antigens. This study characterizes the role of LT and its non-toxic B subunit (LTB) in the modulation of antibody responses to a coadministered antigen, the dengue virus (DENV) envelope glycoprotein domain III (EDIII), which binds to surface receptors and mediates virus entry into host cells. In contrast to non-adjuvanted or alum-adjuvanted formulations, antibodies induced in mice immunized with LT or LTB showed enhanced virus-neutralization effects that were not ascribed to a subclass shift or antigen affinity. Nonetheless, immunosignature analyses revealed that purified LT-adjuvanted EDIII-specific antibodies display distinct epitope-binding patterns with regard to antibodies raised in mice immunized with EDIII or the alum-adjuvanted vaccine. Notably, the analyses led to the identification of a specific EDIII epitope located in the EF to FG loop, which is involved in the entry of DENV into eukaryotic cells. The present results demonstrate that LT and LTB modulate the epitope specificity of antibodies generated after immunization with coadministered antigens that, in the case of EDIII, was associated with the induction of neutralizing antibody responses. These results open perspectives for the more rational development of vaccines with enhanced protective effects against DENV infections.View the article as published at https://www.frontiersin.org/articles/10.3389/fimmu.2017.01175/ful
Point Protection of Primary Beams of Steel Grillages Against Lateral Torsional Buckling
No full textThe paper deals with the analysis of lateral torsional buckling (LTB) of steel beams that are components of grillages. Such structures are constructed from primary substring beams and secondary coupling beams. One of the functions performed by secondary beams in grillages is point protection of primary beams against overall stability failure. Based on the LTB analysis of primary beams, the condition specified in the code PN-EN 1993-1-1 (EC-3) was verified. The condition concerns the maximum spacing of point lateral bracings that stabilise compression flanges of beams. Critical moments of LTB for those beams were determined employing two methods. The first method involved the use of equivalent (simplified) loading diagram and the author-developed analytic formula. The other method employed LTBeamN and Abaqus (FEM) software, in which the whole beam was modelled together with bracings. Beam loading diagrams most frequently used in engineering practice were taken into account. Coefficients of LTB were determined in accordance with EC-3. A good congruence of results was obtained, which confirmed the correctness of the equivalent (simplified) beam loading diagram. The condition specified in the code PN-EN 1993-1-1 (EC-3) was also confirmed
Lateral torsional buckling of welded wide flange beams under constant moment
No full textThe structural steel design specification in Canada, CSA S16-14, uses the same equations for the design of rolled and welded shape beams for lateral torsional buckling (LTB). A recent study has shown that the current design equations might overestimate the capacity of welded wide flange (WWF) beams. This paper evaluates the performance of the current design equations in providing LTB capacities of welded I-shape beams (WWF beams). An extensive FE analysis is performed for simply supported WWF beams subjected to constant moment. In total, 256 FE models are analysed and it is observed that both CSA and AISC overestimate the LTB capacity of welded I-shape beams by as much as 37%, particularly when residual stress measured at Lehigh is used in analysis. Also, the Eurocode is found to be conservative and the proposed equation by MacPhedran and Grondin (2011) provides better predictions of LTB strengths of WWF shapes than the current CSA approach.The accepted manuscript in pdf format is listed with the files at the bottom of this page. The presentation of the authors' names and (or) special characters in the title of the manuscript may differ slightly between what is listed on this page and what is listed in the pdf file of the accepted manuscript; that in the pdf file of the accepted manuscript is what was submitted by the author
EFFECTS OF SHEAR STRESS ON PLATELET - POLYMORPHONUCLEAR LEUKOCYTE INTERACTIONS (LTB(4), AGGREGATION)
No full textThe effects of shear stress on platelet - polymorphonuclear leukocyte (PMNL) interactions were studied to ascertain whether mechanical trauma induces PMNL aggregation or degranulation. PMNL suspensions were exposed to shear stresses up to 150 dynes/cm('2) at room temperature for 1 minute. PMNL responses were monitored by the following measurements. The large particle percentage was calculated from Coulter counter data to indicate shear-induced aggregation. (beta)-glucuronidase in the extracellular fluid was assayed to indicate azurophilic granule release. Lactate dehydrogenase (LDH) release was measured to indicate cell lysis.
PMNL suspensions in buffer showed no aggregate formation or enzyme release at shear stresses below 150 dynes/cm('2) for an exposure time of 1 minute. However, supernatant plasma from sheared platelet rich plasma (PRP) initiated PMNL aggregation and (beta)-glucuronidase release at this shear stress. In contrast, platelet release factors, such as ADP and serotonin did not cause PMNL aggregation.
The use of a cyclooxygenase inhibitor (aspirin) did not suppress the aggregation of PMNLs after shear. However, preincubation with lipoxygenase inhibitors (U-60257 and nordihydroguaiaretic acid) suppressed aggregation and enzyme release.
The shear-induced enzyme release was enhanced by cytochalasin B and heparinized samples showed greater effects than citrated samples.
The effects of shear stress on whole blood aggregation also were studied. The total aggregate volume and mean channel number were calculated.
Blood samples sheared at 37(DEGREES)C showed much less aggregation than those sheared at room temperature. The total aggregate volume and mean aggregate size were decreased at the increased temperature. Heparinized blood was more sensitive to shear stress than citrated samples. A cyclooxygenase inhibitor (aspirin) was ineffective in reducing shear-induced aggregation. However, a lipoxygenase inhibitor (nordihydroguaiaretic acid) was effective in reducing aggregate size.
The formation of arachidonic acid metabolities activated by shear stress was documented by reversed phase - high performance liquid chromatography (RP-HPLC). Thus, an interaction between C-12 and C-5 lipoxygenase enzymes can promote the formation of leukotriene B(,4)(LTB(,4)) and these data support the possibility of cooperation between platelet and PMN leukocyte arachidonic acid metabolites leading to a mechanically induced cell activation. (Abstract shortened with permission of author.
Age problem in Lemaître–Tolman–Bondi void models
No full textAbstractAs is well known, one can explain the current cosmic acceleration by considering an inhomogeneous and/or anisotropic universe (which violates the cosmological principle), without invoking dark energy or modified gravity. The well-known one of this kind of models is the so-called Lemaître–Tolman–Bondi (LTB) void model, in which the universe is spherically symmetric and radially inhomogeneous, and we are living in a locally underdense void centered nearby our location. In the present work, we test various LTB void models with some old high redshift objects (OHROs). Obviously, the universe cannot be younger than its constituents. We find that an unusually large r0 (characterizing the size of the void) is required to accommodate these OHROs in LTB void models. There is a serious tension between this unusually large r0 and the much smaller r0 inferred from other observations (e.g. SNIa, CMB and so on). However, if we instead consider the lowest limit 1.7 Gyr for the quasar APM 08279+5255 at redshift z=3.91, this tension could be greatly alleviated
Lateral-torsional buckling resistance of non-prismatic and prismatic mono-symmetric I-section steel beams based on stress utilization
No full textThe lateral-torsional resistance of prismatic double-symmetric I-section beams is accurately predicted using a mechanically consistent Ayrton-Perry approach, combined with a calibrated generalized imperfection. The corresponding design formulation was recently adopted in the revised version of Eurocode 3. However, for prismatic mono-symmetric I-section beams, the General Case shall be used while for non-prismatic beams only the General Method is available. Both methods present a very large scatter and highly underestimate the lateral-torsional buckling resistance. This paper proposes an extension to the General Formulation for non-prismatic beams with arbitrary boundary conditions, partial lateral restraints, and arbitrary loading for mono-symmetric I-sections. Using an advanced numerical model calibrated with experimental test results, a large parametric study is undertaken, and its results are used to assess the available design methodologies and the proposed method. It is concluded that the General Formulation provides excellent safe-sided estimates of the LTB resistance, and it is confirmed the very poor performance of the General Case and the General Method.Steel & Composite Structure
Baseline gene expression profiling determines long-term benefit to programmed cell death protein 1 axis blockade
No full textTreatment with immune checkpoint inhibitors has altered the course of malignant melanoma, with approximately half of the patients with advanced disease surviving for more than 5 years after diagnosis. Currently, there are no biomarker methods for predicting outcome from immunotherapy. Here, we obtained transcriptomic information from a total of 105 baseline tumor samples comprising two cohorts of patients with advanced melanoma treated with programmed cell death protein 1 (PD-1)-based immunotherapies. Gene expression profiles were correlated with progression-free survival (PFS) within consecutive clinical benefit intervals (i.e., 6, 12, 18, and 24 months). Elastic net binomial regression models with cross validation were utilized to compare the predictive value of distinct genes across time. Lasso regression was used to generate a signature predicting long-term benefit (LTB), defined as patients who remain alive and free of disease progression at 24 months post treatment initiation. We show that baseline gene expression profiles were consistently able to predict long-term immunotherapy outcomes with high accuracy. The predictive value of different genes fluctuated across consecutive clinical benefit intervals, with a distinct set of genes defining benefit at 24 months compared to earlier outcomes. A 12-gene signature was able to predict LTB following anti-PD-1 therapy with an area under the curve (AUC) equal to 0.92 and 0.74 in the training and validation set, respectively. Evaluation of LTB, via a unique signature may complement objective response classification and characterize the logistics of sustained antitumor immune responses. © 2022, The Author(s)
Macrophage produced IL-12p70 mediates hemorrhage-induced damage in a complement dependent manner
No full textHemorrhage and hemorrhagic shock instigate intestinal damage and inflammation. Multiple components of the innate immune response, including complement and neutrophil infiltration, are implicated in this pathology. To investigate the interaction of complement activation and other components of the innate immune response during hemorrhage, we treated mice post-hemorrhage with CR2-fH, a targeted inhibitor of the alternative complement pathway and assessed intestinal damage and inflammation 2 h after hemorrhage. In wildtype mice, CR2-fH attenuated hemorrhage-induced, mid-jejunal damage and inflammation as determined by decreased mucosal damage, macrophage infiltration, LTB[subscript 4], IL-12p40, and TNF-α production. The critical nature of intestinal macrophage infiltration and activation in the response to hemorrhage was further determined using mice pre-treated with clodronate containing liposomes. The absence of either macrophages or IL-12p70 attenuated intestinal damage. These data suggest that complement activation and macrophage infiltration with IL-12p70 production are critical to hemorrhage induced mid-jejunal damage and inflammation
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