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In general, eigenvalue analysis for beams considering rotatory inertia and shear deformation is not trivial, even in the case of uniform beams. In this paper, a practical method is proposed for calculating natural bending frequencies of uniform elastic beams considering rotatory inertia and shear deformation. The proposed method is based on the modified Timoshenko beam theory, which is more rigorous and realistic than the traditional Timoshenko beam theory. It is shown that the proposed method calculates the natural frequencies of an arbitrary order-vibration mode for beams of arbitrary cross-sections with a high level of accuracy, similar to numerical analysis.

The difference in sequential organ failure assessment (SOFA) scores from the baseline to sepsis is a known predictor of sepsis-3 outcome, but the prognostic value of drug-resistant organisms for mortality is unexplained. We employed sepsis stewardship and herein report an observational study. Study subjects were patients admitted to the Departments of Surgery/Chest Surgery from 2011 through 2018 with a diagnosis of sepsis and a SOFA score of 2 or more. Our sepsis stewardship methods included antimicrobial and diagnostic stewardship and infection control. We determined the primary endpoint as in-hospital death and the secondary endpoint as the annual trend of the risk-adjusted mortality ratio (RAMR). For mortality, we performed logistic regression analysis based on SOFA score, age, sex, comorbid disease, and the presence of methicillin-resistant Staphylococcus aureus (MRSA) and extended-spectrum beta-lactamase inhibitor–producing bacteria. In a total of 457 patients, two factors were significant predictors for fatality, i.e., SOFA score of 9 or more with an odds ratio (OR) 4.921 and 95% confidence interval [95% CI] 1.968–12.302 (P = 0.001) and presence of MRSA with an OR 1.83 and 95% CI 1.003–3.338 (P = 0.049). RAMR showed a decrease during the study years (P < 0.05). Early detection of MRSA may help patients survive surgical sepsis-3. Thus, MRSA-oriented diagnosis may play a role in expediting treatment with anti-MRSA antimicrobials.

This study topologically describes near-wall flows around a surface-mounted cylinder at a high Reynolds number ( $Re$ ) of $5\times 10^4$ and in a very thick boundary layer, which were partially measured or technically approximated from the literature. For complete and rational flow construction, we use high-resolution simulations and critical-point theory. The large-scale near-wake vortex is composed of two connected segments rolled up from the sides of the cylinder and from the free end. Another large-scale side vortex clearly roots on two notable foci on the lower side wall. In the junction region, the side vortex moves upwards with a curved trajectory, which induces the formation of nodes on the ground surface. In the free-end region, the side vortex is compressed, which results in a smaller trailing-edge vortex and its downstream movement. Only tip vortices are observed in the far wake. The origin of the tip vortices and their distinction from the near-wake vortex are discussed. Further analyses suggest that $Re$ independence should be treated with high caution when $Re$ increases from 500 to ${O}(10^4)$ . The occurrence of upwash flow behind the cylinder strongly depends on the increase in $Re$ , the mechanism of which is also provided. The separation–reattachment process in the junction region and the trailing-edge vortices are discovered only at a high $Re$ . The former should significantly affect the strength of the side vortex in the junction region and the latter should cause a sharp drop in pressure near the trailing edge.

Purpose To reduce Clostridioides difficile infection (CDI), we implemented interprofessional antimicrobial, infection control, and diagnostic stewardship (ipAS) conducted by physicians/pharmacists, infection control nurses, and medical technologists, respectively. As a numerical indicator for ipAS, we used antimicrobial use density (AUD) in an 8-year study to validate its efficacy in CDI reduction. Patients and methods This was an observational study. CDI was defined as stool samples or C. difficile isolates containing toxin A and/or B from a patient with diarrhea occurring three or more times per day. From 2011-2018 at a 10-ward single site the subjects were in-patients with CDI, and the following data were collected: AUDs for 23 antibiotics, and antimicrobial test results. By 2015, we had established ipAS, consisting of culture submission before the administration of broad-spectrum antimicrobials, the promotion of point-of-care testing for diagnosis-based antimicrobials, perioperative prophylactic antibiotics, intervention at positive diagnosis of blood culture, team round for diarrhea, and inspection on contact precautions and disinfection in CDI cases. The study outcomes included annual numbers of CDI patients and blood culture sets. We compared annual AUDs between former (2011-14) and latter (2015-18) periods using Kruskal-Wallis tests and examined the correlation between AUDs and CDI numbers. Results Of a total 50,970 patients, 1,750 patients underwent C. difficile toxin tests, of whom 171 patients (9.8%) were positive for CDI. Between the former and latter periods, AUDs for flomoxef (11.96 to 2.71 by medians), panipenem/betamipron (0.30 to 0.00), and clindamycin (3.87 to 2.19) significantly decreased (P

Windborne debris is caused by severe wind events, such as typhoons and tornadoes. Among the various shapes, sheet-shaped debris has especially complex flight behavior due to the Magnus effect induced by autorotation. In this study, we simulate flows past an autorotating flat square plate pinned with a freely rotatable axis (one degree-of-freedom) and a free-flight flat square plate (six degrees-of-freedom). Therefore, the coupled model for fluid flow and a rigid body based on large-eddy simulation has been developed using the immersed-boundary method and block-structured adaptive mesh refinement to capture details of the vortex structures around the moving plate. This model has such efficiency of computation that the boundary of the moving plate can be treated as passing through a fixed mesh pattern represented by sufficiently fine Cartesian grids, avoiding time-dependent grid generation in a boundary-fitted manner. The aerodynamics of the auto-rotating flat plate was examined and confirmed to validate the present model. Moreover, the unsteady forces based on wake vortices in the process of successive deformation are identified, and their roles on autorotation are clarified. In the case of free flight, the sensitive instability of the axis during autorotation and the effects of translational motion on rotational motion are discussed.

Surface flow patterns on a wall-mounted square cylinder and their relationship with pressure are investigated numerically using a fine Cartesian grid. A combination of the building cube and immersed boundary methods and results, including mean pressure, root mean square (r.m.s) pressure, and flow fields are validated qualitatively and quantitatively through experiments. At an attack angle (α) of 0°, it is found that the mean pressure has a distinct vertical classification, even for short cylinders (aspect ratio of 3 or 4). The side-wall pressures are divided into three categories from bottom to top: “junction region,” “2D-like region,” and “free-end region.” Their borders correspond to two notable saddle points in the side-wall streamlines. The mean base pressures can be classified into “lower region” and “near-wake vortex influence region” in the vertical direction. The base-pressure tendency is similar to the change in wake formation lengths. The border is near the upper end of the attachment line in back-wall streamlines. At α = 15°, the mean pressures on the flow-reattachment wall are classified using the curvature of the attachment line, wherein strong two-dimensional effects arise locally in the 2D-like region. Additionally, the similarity between 2D-like regions and infinite cylinders is discussed.

The effects of planar shear inflows are investigated on flows past a rounded-corner square cylinder at Re = 2.2 × 104. The dimensionless shear parameter K ranges from 0.0 to 1.0. Strong dependency on K is found when K = 0–0.4. At K = 0.1, the flow fully separates on the high- and low-velocity sides despite asymmetry; the shear effects on aerodynamic characteristics have an overall similarity with those of sharp-corner square cylinders. At K = 0.4, the flow topology is changed significantly. Flow reattachment occurs on the high-velocity side, inducing a separation bubble. The low-velocity side is featured by a completely separated shear layer that is farther from the cylinder than at lower K, and by much weaker Karman vortices. This flow pattern results in very small mean pressures near the upper frontal corner, low r.m.s pressures on the bottom wall and a higher Strouhal number. When the local and extreme shear inflow at K = 1.0 is imposed with a high blockage ratio, the alternative vortex shedding is suppressed in the absence of interaction between two shear layers. The wake appears like a turbulent mixing layer which emanates from the trailing corner and rolls up to a series of large-scale coherent structures. However, the lower shear layer stays nearly stationary.

A woman in her 70s developed deep vein thromboembolism(DVT)and pulmonary embolism(PE)during chemotherapy for advanced transverse colon cancer. After the first treatment with heparin and warfarin, the anticoagulant was changed to edoxaban to reduce the risk of bleeding. She continued receiving chemotherapy for 4 years. We recommend edoxaban as the first choice of anticoagulant for patients with DVT and PE requiring chemotherapy with fluoropyrimidine-based antineoplastic agents.

The global background of energy shortages and climate deterioration demands bioclimatic sustainable buildings. Vernacular architecture can provide a useful resource of passive strategies and techniques for creating inner comfort conditions with minimum heating, ventilation, and air conditioning (HVAC) assistance. The identification and verification of such knowledge are essential for climate responsive or energy passive building design. Among the methods, computational fluid dynamics (CFD) is a useful tool for simulating convective heat transfer of vernacular architecture and predicting the convective heat transfer coefficient (CHTC) and flow field. Geometric complexity and diversity of building samples are crucial in the development of an effective simulation methodology in terms of computational cost and accuracy. Therefore, this paper presents high-resolution 3D steady Reynolds-averaged Navier&ndash, Stokes (RANS) CFD simulations of convective heat transfer on Japanese vernacular architecture, namely, &ldquo, machiya.&rdquo, A CFD validation study on the CHTC is performed based on wind-tunnel experiments on a cube heated by constant heat flux and placed in a turbulent channel flow with a Reynolds number of 3.3 &times, 104. Three steady RANS models and two boundary layer modeling approaches are compared and discussed. Results show that the SST k-&omega, model applied with low Reynolds number modeling approach is suitable for CHTC simulations on a simplified building model. The RNG k-&epsilon, model applied with wall functions is an appropriate choice for simulating flow field of a complicated building model. Overall, this study develops a methodology involving RANS model selection, boundary layer modeling, and target model fitting to predict the convective heat transfer on vernacular architecture.

Purpose To reduce Clostridioides difficile infection (CDI), we implemented interprofessional antimicrobial, infection control, and diagnostic stewardship (ipAS) conducted by physicians/pharmacists, infection control nurses, and medical technologists, respectively. As a numerical indicator for ipAS, we used antimicrobial use density (AUD) in an 8-year study to validate its efficacy in CDI reduction. Patients and methods This was an observational study. CDI was defined as stool samples or C. difficile isolates containing toxin A and/or B from a patient with diarrhea occurring three or more times per day. From 2011–2018 at a 10-ward single site the subjects were in-patients with CDI, and the following data were collected: AUDs for 23 antibiotics, and antimicrobial test results. By 2015, we had established ipAS, consisting of culture submission before the administration of broad-spectrum antimicrobials, the promotion of point-of-care testing for diagnosis-based antimicrobials, perioperative prophylactic antibiotics, intervention at positive diagnosis of blood culture, team round for diarrhea, and inspection on contact precautions and disinfection in CDI cases. The study outcomes included annual numbers of CDI patients and blood culture sets. We compared annual AUDs between former (2011–14) and latter (2015–18) periods using Kruskal–Wallis tests and examined the correlation between AUDs and CDI numbers. Results Of a total 50,970 patients, 1,750 patients underwent C. difficile toxin tests, of whom 171 patients (9.8%) were positive for CDI. Between the former and latter periods, AUDs for flomoxef (11.96 to 2.71 by medians), panipenem/betamipron (0.30 to 0.00), and clindamycin (3.87 to 2.19) significantly decreased (P

The epidemiology of patients with traumatic brain injury (TBI) has changed dramatically over recent decades as a result of rapid advances in aging societies. We assessed the influence of age on outcomes of patients with TBI and sought to identify prognostic factors for in-hospital mortality of TBI among elderly patients.Using a nationwide database, we analyzed data from 5651 patients with TBI. Univariate analysis was conducted to compare patient demographics, neurologic status on admission, radiologic findings, systemic complication rates, length of hospital stay, in-hospital mortality, and home discharge rates between elderly and nonelderly groups. Multivariable analysis was conducted to determine prognostic factors for in-hospital mortality among elderly patients.Overall in-hospital mortality was significantly higher in elderly patients (12.8% vs. 19.3%; P0.001). In-hospital mortality of elderly patients with mild TBI increased significantly at7 days after admission, whereas that of elderly patients with moderate or severe TBI was significantly higher immediately after admission. Age (odds ratio [OR], 1.62; P = 0.024), male sex (OR, 1.30; P = 0.004), Japan Coma Scale score on admission (OR, 5.95, P0.001), and incidence of acute subdural hematoma (OR, 1.89; P0.001) were associated with in-hospital mortality in elderly patients with TBI.Elderly patients with TBI showed significantly higher in-hospital mortality. Delayed increases in in-hospital mortality were observed among elderly patients with mild TBI. Level of consciousness on admission was the strongest predictor of in-hospital mortality among elderly patients.

Larvae of the blowfly Lucilia sericata facilitate wound healing by removing dead tissue and biofilms from non-healing and necrotic wounds. Another beneficial action of larvae and their excretions/secretions (ES) is down-regulation of excessive inflammation. As prolonged complement activation is key to excessive inflammation, the aim of this study was to elucidate the mechanisms underlying the anti-complement activities of ES. Results revealed that heat sensitive serine proteases in ES degrade multiple complement proteins in all steps of the three complement activation pathways. Importantly, C3a and C5a-major activators of inflammation-were also degraded by ES and pretreatment of these factors with ES completely blocked their ability to induce activation of human neutrophils. Pre-exposure of the neutrophils to ES did not affect their responsiveness to C3a/C5a and fMLP, indicating that the receptors for these activators on neutrophils were not affected by ES. Surprisingly, heat and serine protease inhibitor pretreatment did not affect the ability of ES to inhibit C5b-9 complex formation despite degrading complement proteins, indicating a second complement-inhibiting molecule in ES. Heated ES was as effective as intact ES in inhibiting C3 deposition upon activation of the alternative pathway, but was significantly less effective in wells with a classical or lectin pathway-specific coating. Unfortunately, the molecules affecting the complement system could not be identified due to an insufficient database for L. sericata. Together, larval ES inhibit complement activation by two different mechanisms and down-regulate the C3a/C5a-mediated neutrophil activation. This attenuates the inflammatory process, which may facilitate wound healing.

The authors report the case of a mobile spinal enterogenous cyst in a 2-year-old boy, who was admitted to the hospital several times for intermittent paraplegia. Magnetic resonance imaging and CT revealed an isolated cyst in the lumbar spinal canal. The symptoms were caused by transient myelopathy of the conus medullaris and radiculopathy of the cauda equina due to the changing size and location of the cyst. The cyst was surgically extirpated, after which the symptoms resolved. The histopathological diagnosis was enterogenous cyst. The clinical history of intraspinal enterogenous cyst is usually progressive. Mobility and changes in size are rare pathophysiological findings. The authors speculate that the cyst wall did not adhere to the surrounding structures and had ruptured and quickly reformed. Enterogenous cyst should be considered in the differential diagnosis of spinal intradural cysts in children with radiculomyelopathy.

To validate applicability of the novel hybrid meteorological model/engineering LES method to damage estimation of actual tornado events, simulation is performed focusing on the severely damaged area of the strong tornado on May 6, 2012 in the city of Tsukuba with the realistic tornado structure reproduced in the meteorological model, the actual building distribution, and the topography. The flows over the disaster-affected low-rise residential area show an evident converging character at a height close to the rooftops. Intense strong wind bands are formed by the influence of the buildings. The simulated maximum wind gust is compared with the distribution of actual building damage. It reveals that the hybrid method can reasonably estimate distribution of the building damage over the target area in the tornado event. The track nevertheless exhibits building-scale perturbation that may be attributed to chaotic randomness of the tornado behavior on the complex rough surface. Using the simulated aerodynamic force, simplified case studies on the occurrence and process of damage to two individual buildings is also presented.

Numerical simulations with high grid resolutions are conducted to investigate the flow past a square cylinder at the Reynolds number of 2 . 2 × 1 0 4 and the critical angle of attack of 14 ° . The focus is on the unsteadiness with a much lower frequency than that of von Karman vortex shedding. This study confirms the existence of low-frequency unsteadiness even for the square cylinder. The qualitative and quantitative features of low-frequency unsteadiness are systematically analyzed in terms of forces, vortex shedding and separation bubble. The low frequency with the outstanding peak is much lower than the frequency of von Karman vortex shedding; specifically, it is about 0 . 14 f v K , where f v K is the vortex-shedding frequency. The low-frequency unsteadiness can be “felt” in the time series of forces and in the dynamics of vortex shedding and separation bubble. For both drag and lift, the unsteadiness is manifested by the low-frequency modulation of force amplitude and by the low-frequency periodic variation between the high and low values of the mean drag and lift over a vortex shedding cycle. The smaller force amplitude is accompanied simultaneously by the vortex shedding with longer formation length and weaker spanwise correlation, together with longer separation bubble on the flow-reattachment side of the cylinder.

To evaluate the aerodynamic instability for buildings considering their high-order oscillation mode and torsional oscillation mode on which it is difficult to perform the usual wind tunnel experiments, the fluid–structure interaction (FSI) analysis code combined with a multi-degree-of-freedom structure model and large-eddy simulation was developed. The calculation results obtained in this study and the results of wind tunnel tests conducted in a previous study using a building model (average breadth 0.14 ​m ​× ​length 0.28 ​m ​× ​height 1 ​m; scale: 1/600) with a multi-degree-of-freedom structure were compared. The comparison showed that the FSI analysis results were corresponded well with those of the wind tunnel tests; for each spectrum of response displacement (wind, along-wind, and torsional direction) at the top mass node, the frequency distribution and the peak frequency of the first and second oscillation modes were in good agreement with the calculation results and the wind tunnel test results. As for the amplitude of the top displacement of the building, the results for both the along- and across-wind directions showed good correspondence. For the torsional direction, the calculation results reproduced a torsional flutter oscillation with a slightly low wind level in comparison with that observed in the wind tunnel experiments.

In contrast with a wide range of applications concerning flows around a circular cylinder at upper subcritical Reynolds numbers (Re), there is no systematic understanding about the fundamentals of so-called random flow patterns, and their effects on intermittent modulations in the time history of pressure or force, and the decrease in their spanwise correlations. This paper employed the large-eddy simulation (LES) technique to predict flows past a circular cylinder at Re=1.3×105 and to provide images based on flow visualization that can clarify the physical mechanism responsible for these outcomes. A reasonably sufficient spanwise length was adopted for the numerical model by taking into consideration the effect of aspect ratios (the spanwise length to the diameter). We found that even at such high Res, a three-dimensional pattern of vortical field is present in the wake resulting in total force modulation and weak spanwise correlation, e.g., obvious oblique shedding. The whole development process of the three-dimensional wake is exhibited as a universal. The results revealed that local phase variations in primary vortex shedding are the starting points of three-dimensional wake patterns, which are induced by the “irregular” streamwise vortex. The three-dimensional near wake following local phase variations is associated with a successive evolution composed of certain stages in order. Quantitative analyses based on the time series of sectional lift coefficients show that intermittent increase in primary shedding periods and sectional lift streak divisions are closely related to local phase variations and vortex division in the development process of the three-dimensional pattern. In addition to the phase difference along the span, the three-dimensional pattern also weakens vortex shedding in cross sections perpendicular to the axis of the cylinder, resulting in modulation of the sectional lift coefficient.

This paper discusses the applicability of large eddy simulation (LES) to the wind-resistant design of buildings in cities. In order to accurately predict wind pressures and forces on actual buildings with complicated shapes, we partially introduce the unstructured grid system, which is formulated on the open-source CFD code. Applying the LES method for modeling the urban flow, where a specified high-rise building focuses on safety under wind loading, the combined model is employed to investigate aerodynamic characteristics. This model uses overset grids, consisting of the Cartesian grid and the unstructured-grids. According to previous studies, the Cartesian grid method can accurately generate the turbulent structures in the urban canopy, whereas the unstructured grid method can reproduce detailed patterns of the near-wake flows around a specified building inside a densely built-up area. In this study, we have applied the combined model consisting of the Cartesian grid and unstructured grid for wind load estimation of a high-rise building in a city. Particularly, at inclined wind direction to the main streets, there is a presumption of different effects of wind impact at each vertical level of a high-rise building along the street. Accordingly, relatively a large torsional force tends to be present. On the basis of the results obtained, their accuracy is checked in comparison with the previous data by wind tunnel experiment, and wind pressure distributions on the surfaces as well as wind force coefficients of a high-rise building are estimated and discussed in view of structural safety.

Induction of bacteriolysis of Vibrio vulnificus cells by 10 mM hydrogen peroxide (H(2)O(2)) was analyzed. All Vibrio species examined, except for Vibrio hollisae, were lysed by 10 mM H(2)O(2). Bacteriophage induction was not the cause of H(2)O(2)-induced bacteriolysis. Autolysis is also known to cause bacteriolysis. VvpS protein is a serine protease of V. vulnificus essential for autolysis. vvpS mutant underwent H(2)O(2)-induced bacteriolysis in the same manner as the wild type. Protease inhibitors including serine protease inhibitors did not inhibit H(2)O(2)-induced bacteriolysis, which means that bacteriolysis is not due to autolysis. Unexpectedly, H(2)O(2)-induced bacteriolysis was accelerated by adding 4-(2-aminoethyl) benzenesulfonyl fluoride hydrochloride (AEBSF) and phenylmethylsulfonyl fluoride which are serine protease inhibitors. The hydroxyl radical was generated by H(2)O(2)-AEBSF interaction. It was considered that H(2)O(2)-induced bacteriolysis was caused by the hydroxyl radical which was generated by Fenton reaction, and possibly mediated by AEBSF. Deferoxamine, an agent chelating ferric ion and Fenton reaction inhibitor, suppressed both H(2)O(2)-induced bacteriolysis and its acceleration by AEBSF. This suggests that both phenomena were Fenton reaction dependent, and hydroxyl radical generated by Fenton reaction caused bacteriolysis of V. vulnificus though the reason for high susceptibility of Vibrio species to hydroxyl radical is not known.

In the past, the coarse spanwise resolution was widely used for high-Reynolds-number flow simulations of a two-dimensional bluff body with the purpose of reducing the computational resources. The effects and requirements of spanwise resolution (dz/D, where D is the width of the cylinder) remain unclear for direct numerical simulation (DNS) or large-eddy simulation (LES). This numerical study, without any explicit subgrid-scale model, focuses on the typical flow around a square cylinder at the Reynolds number of 22,000. dz/D varies between 0.08 and 0.013. The requirement is recommended based on the systematical examination of aerodynamic pressure forces, vortex shedding in the wake, and flow structures in the separating shear layers. dz/D ≈ 0.04 is suggested sufficient for the prediction of mean and r.m.s aerodynamic pressures acting on the cylinder, mean and r.m.s velocity fields and small-scale turbulent motions in the wake. The coarser dz/D causes longer vortex formation length behind the cylinder and smaller fluctuating velocities around the cylinder (except the spanwise component). However, a stricter dz/D ≤ 0.02 is suggested necessary for accurately predicting the shear layer behaviors. Only if this requirement is satisfied, the subharmonic and harmonic of the Kelvin-Helmholtz instability can be captured, together with the process of laminar-turbulent transition in the shear layer. The shear layer when dz/D ≤ 0.02 is composed of interconnected small-scale spanwise and streamwise vortices. The shear layer has greater integrity along the spanwise direction and flaps as a whole at the same pace with vortex shedding. However, the shear-layer spanwise vortices are discrete when dz/D>0.02 as the streamwise vortices are not sufficiently reproduced.

A new hybrid meteorological model/engineering LES method was used to analyze a tornado and near-ground turbulence under realistic conditions. The hybrid method estimates high frequency turbulence regeneration in an actual severe storm that has complex thermal conditions in order to alleviate the problem of high frequency component dissipation in meteorological models and generate appropriate field data to investigate near-ground flow and wind loading on buildings. The high frequency regeneration method was validated in the convective boundary layer and the energy spectrum of the velocity field was successfully extended to higher frequency region in good agreement with −5/3 Kolmogorov law. Multi-scale simulations of a tornado were conducted based on meteorological model outputs with three different terrain conditions, including an actual urban building geometry and terrain, and the changes in the main tornado vortex and the interactions with near-ground turbulent field were examined. On roughened surfaces with uniform blocks and buildings, the main tornado vortex was connected to near-ground vertical vortices arising due to the urban geometry. The structure was significantly deformed, splitting into numerous finer vortices below several times the building height. These near-ground vortices create localized sharp pressure drop patterns and also affect the movement of the tornado. These effects of low pressure on buildings were quantitatively analyzed.

Larvae of the blowfly Lucilia sericata facilitate wound healing by removing dead tissue and biofilms from non-healing and necrotic wounds. Another beneficial action of larvae and their excretions/secretions (ES) is down-regulation of excessive inflammation. As prolonged complement activation is key to excessive inflammation, the aim of this study was to elucidate the mechanisms underlying the anti-complement activities of ES. Results revealed that heat sensitive serine proteases in ES degrade multiple complement proteins in all steps of the three complement activation pathways. Importantly, C3a and C5a-major activators of inflammation-were also degraded by ES and pretreatment of these factors with ES completely blocked their ability to induce activation of human neutrophils. Pre-exposure of the neutrophils to ES did not affect their responsiveness to C3a/C5a and fMLP, indicating that the receptors for these activators on neutrophils were not affected by ES. Surprisingly, heat and serine protease inhibitor pretreatment did not affect the ability of ES to inhibit C5b-9 complex formation despite degrading complement proteins, indicating a second complement-inhibiting molecule in ES. Heated ES was as effective as intact ES in inhibiting C3 deposition upon activation of the alternative pathway, but was significantly less effective in wells with a classical or lectin pathway-specific coating. Unfortunately, the molecules affecting the complement system could not be identified due to an insufficient database for L. sericata. Together, larval ES inhibit complement activation by two different mechanisms and down-regulate the C3a/C5a-mediated neutrophil activation. This attenuates the inflammatory process, which may facilitate wound healing.

Larvae of the blowfly Lucilia sericata facilitate wound healing by removing dead tissue and biofilms from non-healing and necrotic wounds. Another beneficial action of larvae and their excretions/secretions (ES) is down-regulation of excessive inflammation. As prolonged complement activation is key to excessive inflammation, the aim of this study was to elucidate the mechanisms underlying the anti-complement activities of ES. Results revealed that heat sensitive serine proteases in ES degrade multiple complement proteins in all steps of the three complement activation pathways. Importantly, C3a and C5a-major activators of inflammation-were also degraded by ES and pretreatment of these factors with ES completely blocked their ability to induce activation of human neutrophils. Pre-exposure of the neutrophils to ES did not affect their responsiveness to C3a/C5a and fMLP, indicating that the receptors for these activators on neutrophils were not affected by ES. Surprisingly, heat and serine protease inhibitor pretreatment did not affect the ability of ES to inhibit C5b-9 complex formation despite degrading complement proteins, indicating a second complement-inhibiting molecule in ES. Heated ES was as effective as intact ES in inhibiting C3 deposition upon activation of the alternative pathway, but was significantly less effective in wells with a classical or lectin pathway-specific coating. Unfortunately, the molecules affecting the complement system could not be identified due to an insufficient database for L. sericata. Together, larval ES inhibit complement activation by two different mechanisms and down-regulate the C3a/C5a-mediated neutrophil activation. This attenuates the inflammatory process, which may facilitate wound healing.

Recent development of high-performance computers and numerical techniques on wind engineering has enabled us to simulate the complicated flow such as the wind around buildings. Computational Fluid Dynamics (CFD) is expected to be adopted as an applicable technique for evaluating wind load for wind-resistant design of buildings. For numerical prediction of fluctuating wind pressures on buildings, Large Eddy Simulation (LES) is effective to simulate unsteady flows around buildings. The authors performed LES for investigating the wind characteristics in a real urban district. The complicated flow field in an urban area is reproduced by LES using unstructured grid system. Inthis paper, the computed pressures on a tall building are compared with experiments and the applicability of unstructured LES for wind-resistant design of buildings is examined.

Large-eddy simulations were used to investigate the supercritical aerodynamics of a square cylinder with rounded corners in comparison with those in the subcritical regime. First, the numerical methods, especially the dynamic mixed model, were validated on the basis of their prediction of supercritical flows past a circular cylinder. Then, the supercritical flows past a rounded-corner square cylinder were simulated and systematically clarified. Strong Reynolds number (Re) effects existed in the forces and local pressures as Re increased from o(104) to o(106). Changeover of flow patterns occurred as Re increased. At the supercritical Re, the free stream overall flowed along the cross sections of the cylinder, separated from the leeward corners and generated Karman vortices behind the cylinder. This pattern resulted in a much smaller recirculation region behind the cylinder compared with the subcritical flow. At the micro level, the flow experienced laminar separation and flow reattachment near the frontal ...