316 research outputs found
THE PERFORMANCE OF BASE-FORM ION EXCHANGERS FOR pH CONTROL AND REMOVAL OF RADIOISOTOPES FROM A PRESSURIZED WATER REACTOR SYSTEM
Laboratory experiments and in-pile loop tests designed to evaluate, explain, and predict the performance of mixedbed ion exchange columns in the base form for the control of radioisotopes in reactor coolants are summarized. The results of these tests are evaluated with the aid of a simple theory of column performance for absorption of radioactivity decaying ions, based on an approximate model for an ion exchange column. It is concluded that LiOH form resin will perform satisfactorily for both pH control and activity removal and that it is more effective than either KOH resin or NH/sub 4/OH resin for these purposes. (auth
A Novel Assay for Neutrophil Extracellular Trap Formation Independently Predicts Disseminated Intravascular Coagulation and Mortality in Critically Ill Patients
Rationale: Neutrophil extracellular traps (NETs) are important in the host defense against infection, but they also promote intravascular coagulation and multiorgan failure in animal models. Their clinical significance remains unclear, and available assays for patient care lack specificity and reliability. Objectives: To establish a novel assay and test its clinical significance. Methods: A prospective cohort of 341 consecutive adult ICU patients was recruited. The NET-forming capacity of ICU admission blood samples was semiquantified by directly incubating patient plasma with isolated neutrophils ex vivo. The association of NET-forming capacity with Sequential Organ Failure Assessment scores, disseminated intravascular coagulation, and 28-day mortality was analyzed and compared with available NET assays. Measurements and Main Results: Using the novel assay, we could stratify ICU patients into four groups with absent (22.0%), mild (49.9%), moderate (14.4%), and strong (13.8%) NET formation, respectively. Strong NET formation was predominantly found in sepsis (P < 0.0001). Adjusted by Acute Physiology and Chronic Health Evaluation II score, multivariate regression showed that the degree of NET formation could independently predict disseminated intravascular coagulation and mortality, whereas other NET assays (e.g., cell-free DNA, myeloperoxidase, and myeloperoxidase–DNA complexes) could not. IL-8 concentrations were found to be strongly associated with NET formation, and inhibiting IL-8 significantly attenuated NETosis. Mitogen-activated protein kinase activation by IL-8 has been identified as a major pathway of NET formation in patients. Conclusions: This assay directly measures the NET-forming capacity in patient plasma. This could guide clinical management and enable identification of NET-inducing factors in individual patients for targeted treatment and personalized ICU medicine
Circulating Histones Are Major Mediators of Multiple Organ Dysfunction Syndrome in Acute Critical Illnesses.
OBJECTIVES:Multiple organ dysfunction syndrome is characterized by simultaneous multiple organ failure, which is the leading cause of death in acute critically ill patients. However, what mediates multiple organ dysfunction syndrome is not fully understood. The discovery of toxic effects by extracellular histones on different individual organs strongly suggests their involvement in multiple organ dysfunction syndrome. In this study, we investigate whether circulating histones are major mediators of multiple organ dysfunction syndrome in acute critical illnesses. DESIGN:Combination of retrospective clinical studies and animal models with intervention. SETTING:ICU in a tertiary hospital and research laboratories. PATIENTS:Four hundred and twenty ICU patients, including sepsis (140), severe trauma (63), severe pancreatitis (89), and other admission diagnoses (128). LABORATORY INVESTIGATION:Cells from major organs are treated with calf thymus histones or histone-containing sera. Animal models for sepsis, trauma, and acute pancreatitis are treated with antihistone reagents. INTERVENTION:Antihistone reagents in in vitro, ex vivo, and animal models. MEASUREMENT AND MAIN RESULTS:Retrospective analysis of a prospectively recruited ICU cohort demonstrated a strong correlation between circulating histones and organ injury markers and Sequential Organ Failure Assessment scores. Ex vivo experiments showed that patient sera containing high histone levels were toxic to cultured cells from different origins, suggesting their universal toxicity to multiple organs. Animal models of sepsis, trauma, and pancreatitis further demonstrated a temporal correlation between histone levels and disease severity and multiple organ injury. Importantly, antihistone reagents, that is, antihistone single-chain variable fragment and nonanticoagulant heparin, could dramatically reduce multiple organ injury, particularly of the heart and lungs, and improve survival in mouse models. CONCLUSIONS:High levels of circulating histones are major mediators of multiple organ dysfunction syndrome. Our results indicate that monitoring upon ICU admission could inform on disease severity and developing antihistone therapy holds great potential of reducing multiple organ dysfunction syndrome and improving survival of critically ill patients
Extracellular Histones Inhibit Complement Activation through Interacting with Complement Component 4
Abstract
Complement activation leads to membrane attack complex formation, which can lyse not only pathogens but also host cells. Histones can be released from the lysed or damaged cells and serve as a major type of damage-associated molecular pattern, but their effects on the complement system are not clear. In this study, we pulled down two major proteins from human serum using histone-conjugated beads: one was C-reactive protein and the other was C4, as identified by mass spectrometry. In surface plasmon resonance analysis, histone H3 and H4 showed stronger binding to C4 than other histones, with KD around 1 nM. The interaction did not affect C4 cleavage to C4a and C4b. Because histones bind to C4b, a component of C3 and C5 convertases, their activities were significantly inhibited in the presence of histones. Although it is not clear whether the inhibition was achieved through blocking C3 and C5 convertase assembly or just through reducing their activity, the outcome was that both classical and mannose-binding lectin pathways were dramatically inhibited. Using a high concentration of C4 protein, histone-suppressed complement activity could not be fully restored, indicating C4 is not the only target of histones in those pathways. In contrast, the alternative pathway was almost spared, but the overall complement activity activated by zymosan was inhibited by histones. Therefore, we believe that histones inhibiting complement activation is a natural feedback mechanism to prevent the excessive injury of host cells.</jats:p
Simulation of Many-Body Fermi Systems on a Universal Quantum Computer
We provide fast algorithms for simulating many body Fermi systems on a
universal quantum computer. Both first and second quantized descriptions are
considered, and the relative computational complexities are determined in each
case. In order to accommodate fermions using a first quantized Hamiltonian, an
efficient quantum algorithm for anti-symmetrization is given. Finally, a
simulation of the Hubbard model is discussed in detail.Comment: Submitted 11/7/96 to Phys. Rev. Lett. 10 pages, 0 figure
Complexes between C-Reactive Protein and Very Low Density Lipoprotein Delay Bacterial Clearance in Sepsis
Single view silhouette fitting techniques for estimating tennis racket position
Stereo camera systems have been used to track markers attached to a racket, allowing its position to be obtained in three-dimensional (3D) space. Typically, markers are manually selected on the image plane, but this can be time-consuming. A markerless system based on one stationary camera estimating 3D racket position data is desirable for research and play. The markerless method presented in this paper relies on a set of racket silhouette views in a common reference frame captured with a calibrated camera and a silhouette of a racket captured with a camera whose relative pose is outside the common reference frame. The aim of this paper is to provide validation of these single view fitting techniques to estimate the pose of a tennis racket. This includes the development of a calibration method to provide the relative pose of a stationary camera with respect to a racket. Mean static racket position was reconstructed to within ±2 mm. Computer generated camera poses and silhouette views of a full size racket model were used to demonstrate the potential of the method to estimate 3D racket position during a simplified serve scenario. From a camera distance of 14 m, 3D racket position was estimated providing a spatial accuracy of 1.9 ± 0.14 mm, similar to recent 3D video marker tracking studies of tennis
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