Inactivation of Human beta-Defensins 2 and 3 by Elastolytic Cathepsins

beta-Defensins are antimicrobial peptides that contribute to the innate immune responses of eukaryotes. At least three defensins, human beta-defensins 1, 2, and 3 (HBD-1, -2, and -3), are produced by epithelial cells lining the respiratory tract and are active toward Gram-positive (HBD-3) and Gram-negative (HBD-1, -2, and -3) bacteria. It has been postulated that the antimicrobial activity of defensins is compromised by changes in airway surface liquid composition in lungs of patients with cystic fibrosis (CF), therefore contributing to the bacterial colonization of the lung by Pseudomonas and other bacteria in CF. In this report we demonstrate that HBD-2 and HBD-3 are susceptible to degradation and inactivation by the cysteine proteases cathepsins B, L, and S. In addition, we show that all three cathepsins are present and active in CF bronchoalveolar lavage. Incubation of HBD-2 and -3 with CF bronchoalveolar lavage leads to their degradation, which can be completely (HBD-2) or partially (HBD-3) inhibited by a cathepsin inhibitor. These results suggest that beta-defensins are susceptible to degradation and inactivation by host proteases, which may be important in the regulation of beta-defensin activity. In chronic lung diseases associated with infection, overexpression of cathepsins may lead to increased degradation of HBD-2 and -3, thereby favoring bacterial infection and colonization.

Experimental investigation into the temperature and heat transfer distribution around air-cooled cylinders

This paper describes an experimental investigation into the surface heat transfer coefficient of finned metal cylinders in a free air stream. Ten cylinders were tested with four different fin pitches and five different fin lengths. The cylinders and their fins were designed to be representative of those found on a motorcycle engine with an external cylinder diameter of 100 mm and fin lengths of 10 to 50 mm. The fins of each cylinder were gravity die cast in aluminum allow. Each cylinder was electrically heated and mounted in a wind tunnel which subjected it to a range of air speeds between 2 and 20 m/s. The surface heat transfer coefficient, h, was found primarily to be a function of the air speed and the fin separation, with fin length having a lesser effect. In addition to the determination of an overall heat transfer coefficient, the distribution of cooling around the circumference of each cylinder was also studied. Not surprisingly, the cooling was found to be greatest on the front of the cylinder, which was the side first impinged by the air stream. The cooling of the rear of the cylinder was better than might have been expected and this is quantified.

Isolated vibrational wavepackets in D-2(+): Defining superposition conditions and wavepacket distinguishability

Tunnel ionization of room-temperature D-2 in an ultrashort (12 femtosecond) near infrared (800 nm) pump laser pulse excites a vibrational wavepacket in the D-2(+) ions; a rotational wavepacket is also excited in residual D-2 molecules. Both wavepacket types are collapsed a variable time later by an ultrashort probe pulse. We isolate the vibrational wavepacket and quantify its evolution dynamics through theoretical comparison. Requirements for quantum computation (initial coherence and quantum state retrieval) are studied using this well-defined (small number of initial states at room temperature, initial wavepacket spatially localized) single-electron molecular prototype by temporally stretching the pump and probe pulses.

Investigating paediatric airways by non-bronchoscopic lavage: Normal cellular data

Background: Bronchoscopic bronchoalveolar lavage in children to investigate bronchia disorders such as asthtna has both ethical and procedural difficulties.


Objective: The aim of this study was to establish a standardized non-bronchoscopic method to perform bronchoalveolar lavage in children attending for elective surgery to obtain normal cellular data.


Methods: Bronchoalveolar lavage was performed on normal children (n= 55) by infusing saline (20 mL) through an 8 FG suction catheter passed after endotracheal intubation. Oxygen saturation, heart and respiratory rate were monitored during the bronchoalveolar lavage procedure. Cellular analysis and total protein estimation of the lavage fluid were performed. Epithelial lining fluid volume was calculated (n = 15) using the urea dilution method.


Results: The procedure was well tolerated by all children. Total cell count and differential cell count for children (macrophages 70.8 ± 2.3%, lymphocytes 3.8 ± 0.6%, neutrophils 5,7 ± 1.0%, eosinophils 0.14 ± 0.03%. epithelial cells 19.6 ± 2.1%, mast cells 0.21 ± 0.02%) were similar to those reported for adults. Age and sex comparisons revealed no differences between groups. The mean total protein recovered in the cell free supernatant was 49.72 ± 4.29 mg/L and epithelial lining fluid volume was 0.82 ± 0.11% of return lavageate.


Conclusion This method allows bronchoalveolar lavage to be performed safely and quickly on children attending for routine elective surgery. Using this method and taking the ‘window of opportunity’ of elective surgery, the presence or absence of airway inflammation could be studied in children with various patterns of asthma during relatively asymptomatic periods.

Burrow architecture and digging activity in the Cape dune mole rat

While females are traditionally thought to invest more time and energy into parental care than males, males often invest more resources into searching and displaying for mates, obtaining mates and in male-male conflict. Solitary subterranean mammals perform these activities in a particularly challenging niche, necessitating energetically expensive burrowing to both search for mates and forage for food. This restriction presumably affects males more than females as the former are thought to dig longer tunnels that cover greater distances to search for females. We excavated burrow systems of male and female Cape dune mole rats Bathyergus suillus the, largest truly subterranean mammal, to investigate whether male burrows differ from those of females in ways that reflect mate searching by males. We consider burrow architecture (length, internal dimensions, fractal dimension of tunnel systems, number of nesting chambers and mole mounds on the surface) in relation to mating strategy. Males excavated significantly longer burrow systems with higher fractal dimensions and larger burrow areas than females. Male burrow systems were also significantly farther from one another than females were from other females' burrow systems. However, no sex differences were evident in tunnel cross-sectional area, mass of soil excavated per mound, number of mounds produced per unit burrow length or mass of soil excavated per burrow system. Hence, while males may use their habitat differently from females, they do not appear to differ in the dimensions of the tunnels they create. Thus, exploration and use of the habitat differs between the sexes, which may be a consequence of sex differences in mating behaviour and greater demands for food.

Durability and water absorption properties of surface treated concretes

Durability of concrete can be improved by applying surface treatments. Pore-lining treatments prevent or delay the ingress of water-borne salts while allowing vapour transfer across the concrete surface. The most common pore-liners are silanes and siloxanes; both reported to give good results. One area of concern, however, is variability in effectiveness of the treatment. This variability may be due to inconsistent coverage or extreme drying conditions. With care these can be controlled but another source of variability which is difficult to control is the moisture profile within the concrete at the time of application of the treatment. This paper describes a test programme to assess the sensitivity of three different surface treatments to moisture gradient in the concrete at the time of application of treatment. The test programme included durability parameters such as chloride ingress, corrosion due to chloride ingress, freeze-thaw salt scaling resistance. Water absorption (sorptivity) of treated and untreated concretes was also measured with a non-distructive test technique called Autoclam with the aim of determining if the Autoclam sorptivity test can be used to assess the effectiveness of surface treatments. Using these results it is possible to avoid, or allow for, moisture conditions which would adversely affect the success of a pore-liner. However there are advantages in specifying an expected performance of the surface treatment rather than specifying the conditions in which it must be placed. By this method a treatment would have to achieve a specified value of sorptivity or a specified reduction in sorptivity. Failure to do so would be an objective basis on which to make a decision of whether or not to reject the treatment. The Autoclam is a device capable of measuring sorptivity values down to the range typical of surface treated concrete. The paper assesses if the device can be used to discriminate between acceptable treatment and unsatisfactory treatments.

Quasi-classical model of non-destructive wavepacket manipulation by intense ultrashort nonresonant laser pulses

A quasi-classical model (QCM) of nuclear wavepacket generation, modification and imaging by three intense ultrafast near-infrared laser pulses has been developed. Intensities in excess of 10(13) W cm(-2) are studied, the laser radiation is non-resonant and pulse durations are in the few-cycle regime, hence significantly removed from the conditions typical of coherent control and femtochemistry. The 1s sigma ground state of the D-2 precursor is projected onto the available electronic states in D-2(+) (1s sigma(g) ground and 2p sigma(u) dissociative) and D+ + D+ (Coulomb explosion) by tunnel ionization by an ultrashort 'pump' pulse, and relative populations are found numerically. A generalized non-adiabatic treatment allows the dependence of the initial vibrational population distribution on laser intensity to be calculated. The wavepacket is approximated as a classical ensemble of particles moving on the 1s sigma(g) potential energy surface (PES), and hence follow trajectories of different amplitudes and frequencies depending on the initial vibrational state. The 'control' pulse introduces a time-dependent polarization of the molecular orbital, causing the PES to be modified according to the dynamic Stark effect and the transition dipole. The trajectories adjust in amplitude, frequency and phase-offset as work is done on or by the resulting force; comparing the perturbed and unperturbed trajectories allows the final vibrational state populations and phases to be determined. The action of the 'probe' pulse is represented by a discrete internuclear boundary, such that elements of the ensemble at a larger internuclear separation are assumed to be photodissociated. The vibrational populations predicted by the QCM are compared to recent quantum simulations (Niederhausen and Thumm 2008 Phys. Rev. A 77 013404), and a remarkable agreement has been found. The applicability of this model to femtosecond and attosecond time-scale experiments is discussed and the relation to established femtochemistry and coherent control techniques are explored.

Redistribution of vibrational population in a molecular ion with nonresonant strong-field laser pulses

We present an experimental demonstration of nonresonant manipulation of vibrational states in a molecule by an intense ultrashort laser pulse. A vibrational wave packet is generated in D-2(+) through tunnel ionization of D-2 by a few-cycle pump pulse. A similar control pulse is applied as the wave packet begins to dephase so that the dynamic Stark effect distorts the electronic environment of the nuclei, transferring vibrational population. The time evolution of the modified wave packet is probed via the D-2(+) photodissociation yield that results from the application of an intense probe pulse. Comparing the measured yield with a quasiclassical trajectory model allows us to determine the redistribution of vibrational population caused by the control pulse. ©

Validation study for prediction of iced aerofoil aerodynamics

Ice accretions can significantly change the aerodynamic performance of wings and rotor blades. Significant performance degradation can occur when ice accreations cause regions of separated flow, to predict this change implies, at a minimum, the solution of the Reynolds-Averaged Navier-Stokes equations. This paper presents validation for two generic cases involving the flow over aerofoil sections with added synthetic ice shapes. Results were obtained for two aerofoils, namely the NACA 23012 and a generic multi-element configuration. These results are compared with force and pressure coefficient measurements obtained in the NASA LTPT wind-tunnel for the NACA 23012, and force, PIV and boundary-layer measurements obtained at DNW for the multi-clement case. The level of agreement is assessed in the context of industrial requirements.

Framework for Establishing Limits of Tabular Aerodynamic Models for Flight Dynamics Analysis

This paper describes the use of the Euler equations for the generation and testing of tabular aerodynamic models for flight dynamics analysis. Maneuvers for the AGARD Standard Dynamics Model sharp leading-edge wind-tunnel geometry are considered as a test case. Wind-tunnel data is first used to validate the prediction of static and dynamic coefficients at both low and high angles, featuring complex vortical flow, with good agreement obtained at low to moderate angles of attack. Then the generation of aerodynamic tables is described based on a data fusion approach. Time-optimal maneuvers are generated based on these tables, including level flight trim, pull-ups at constant and varying incidence, and level and 90 degrees turns. The maneuver definition includes the aircraft states and also the control deflections to achieve the motion. The main point of the paper is then to assess the validity of the aerodynamic tables which were used to define the maneuvers. This is done by replaying them, including the control surface motions, through the time accurate computational fluid dynamics code. The resulting forces and moments are compared with the tabular values to assess the presence of inadequately modeled dynamic or unsteady effects. The agreement between the tables and the replay is demonstrated for slow maneuvers. Increasing rate maneuvers show discrepancies which are ascribed to vortical flow hysteresis at the higher rate motions. The framework is suitable for application to more complex viscous flow models, and is powerful for the assessment of the validity of aerodynamics models of the type currently used for studies of flight dynamics.

Hydraulic Subsurface Measurements and Hydrodynamic Modeling as Indicators for Groundwater Flow Systems in the Rotondo Granite, Central Alps (Switzerland)

Regional groundwater flow in high mountainous terrain is governed by a multitude of factors such as geology, topography, recharge conditions, structural elements such as fracturation and regional fault zones as well as man-made underground structures. By means of a numerical groundwater flow model, we consider the impact of deep underground tunnels and of an idealized major fault zone on the groundwater flow systems within the fractured Rotondo granite. The position of the free groundwater table as response to the above subsurface structures and, in particular, with regard to the influence of spatial distributed groundwater recharge rates is addressed. The model results show significant unsaturated zones below the mountain ridges in the study area with a thickness of up to several hundred metres. The subsurface galleries are shown to have a strong effect on the head distribution in the model domain, causing locally a reversal of natural head gradients. With respect to the position of the catchment areas to the tunnel and the corresponding type of recharge source for the tunnel inflows (i.e. glaciers or recent precipitation), as well as water table elevation, the influence of spatial distributed recharge rates is compared to uniform recharge rates. Water table elevations below the well exposed high-relief mountain ridges are observed to be more sensitive to changes in groundwater recharge rates and permeability than below ridges with less topographic relief. In the conceptual framework of the numerical simulations, the model fault zone has less influence on the groundwater table position, but more importantly acts as fast flow path for recharge from glaciated areas towards the subsurface galleries. This is in agreement with a previous study, where the imprint of glacial recharge was observed in the environmental isotope composition of groundwater sampled in the subsurface galleries. Copyright © 2012 John Wiley & Sons, Ltd.

Early target cells of measles virus after aerosol infection of non-human primates

Measles virus (MV) is highly infectious, and has long been thought to enter the host by infecting epithelial cells of the respiratory tract. However, epithelial cells do not express signaling lymphocyte activation molecule (CD150), which is the high-affinity cellular receptor for wild-type MV strains. We have generated a new recombinant MV strain expressing enhanced green fluorescent protein (EGFP), based on a wild-type genotype B3 virus isolate from Khartoum, Sudan (KS). Cynomolgus macaques were infected with a high dose of rMV(KS)EGFP by aerosol inhalation to ensure that the virus could reach the full range of potential target cells throughout the entire respiratory tract. Animals were euthanized 2, 3, 4 or 5 days post-infection (d.p.i., n?=?3 per time point) and infected (EGFP(+)) cells were identified at all four time points, albeit at low levels 2 and 3 d.p.i. At these earliest time points, MV-infected cells were exclusively detected in the lungs by fluorescence microscopy, histopathology and/or virus isolation from broncho-alveolar lavage cells. On 2 d.p.i., EGFP(+) cells were phenotypically typed as large mononuclear cells present in the alveolar lumen or lining the alveolar epithelium. One to two days later, larger clusters of MV-infected cells were detected in bronchus-associated lymphoid tissue (BALT) and in the tracheo-bronchial lymph nodes. From 4 d.p.i. onward, MV-infected cells were detected in peripheral blood and various lymphoid tissues. In spite of the possibility for the aerosolized virus to infect cells and lymphoid tissues of the upper respiratory tract, MV-infected cells were not detected in either the tonsils or the adenoids until after onset of viremia. These data strongly suggest that in our model MV entered the host at the alveolar level by infecting macrophages or dendritic cells, which traffic the virus to BALT or regional lymph nodes, resulting in local amplification and subsequent systemic dissemination by viremia.

Controlled redistribution of vibrational population by few-cycle strong-field laser pulses

The use of strong-field (i.e. intensities in excess of 10(13) Wcm(-2)) few-cycle ultrafast (durations of 10 femtoseconds or less) laser pulses to create, manipulate and image vibrational wavepackets is investigated. Quasi-classical modelling of the initial superposition through tunnel ionization, wavepacket modification by nonadiabatically altering the nuclear environment via the transition dipole and the Stark effect, and measuring the control outcome by fragmenting the molecule is detailed. The influence of the laser intensity on strong-field ultrafast wavepacket control is discussed in detail: by modifying the distribution of laser intensities imaged, we show that focal conditions can be created that give preference to this three-pulse technique above processes induced by the pulses alone. An experimental demonstration is presented, and the nuclear dynamics inferred by the quasi-classical model discussed. Finally, we present the results of a systematic investigation of a dual-control pulse scheme, indicating that single vibrational states should be observable with high fidelity, and the populated state defined by varying the arrival time of the two control pulses. The relevance of such strong-field coherent control methods to the manipulation of electron localization and attosecond science is discussed.

Implementation of Menter's Transition Model on an Isolated Natural Laminar Flow Nacelle

This study evaluates the implementation of Menter's gamma-Re-theta Transition Model within the CFX12 solver for turbulent transition prediction on a natural laminar flow nacelle. Some challenges associated with this type of modeling have been identified. The computational fluid dynamics transitional flow simulation results are presented for a series of cruise cases with freestream Mach numbers ranging from 0.8 to 0.88, angles of attack from 2 to 0 degrees, and mass flow ratios from 0.60 to 0.75. These were validated with a series of wind-tunnel tests on the nacelle by comparing the predicted and experimental surface pressure distributions and transition locations. A selection of the validation cases are presented in this paper. In all cases, computational fluid dynamics simulations agreed reasonably well with the experiments. The results indicate that Menter's gamma-Re-theta Transition Model is capable of predicting laminar boundary-layer transition to turbulence on a nacelle. Nonetheless, some limitations exist in both the Menter's gamma-Re-theta Transition Model and in the implementation of the computational fluid dynamics model. The implementation of a more comprehensive experimental correlation in Menter's gamma-Re-theta Transition Model, preferably the ones from nacelle experiments, including the effects of compressibility and streamline curvature, is necessary for an accurate transitional flow simulation on a nacelle. In addition, improvements to the computational fluid dynamics model are also suggested, including the consideration of varying distributed surface roughness and an appropriate empirical correction derived from nacelle experimental transition location data.

IMMUNOCYTOCHEMICAL DEMONSTRATION OF A SALMFAMIDE-LIKE NEUROPEPTIDE IN THE NERVOUS-SYSTEM OF ADULT AND LARVAL STAGES OF THE HUMAN BLOOD FLUKE, SCHISTOSOMA-MANSONI

The localization and distribution of SALMFamide immunoreactivity (IR), SI(GFNSALMFamide), in the nervous system of both the adult and larval stages of the trematode Schistosoma mansoni has been determined by an indirect immunofluorescent technique in conjunction with confocal scanning laser microscopy (CSLM). Immunostaining was widespread in the nervous system of adult male and female S. mansoni. In the central nervous system (CNS), IR was evident in nerve cells and fibres in the anterior ganglia, cerebral commissure and dorsal and ventral nerve cords. In the peripheral nervous system (PNS), IR was apparent in nerve plexuses associated with the subtegmental musculature, oral and ventral suckers, the lining of the gynaecophoric canal, and in fine nerve fibres innervating the dorsal tubercles of the male worm. In the reproductive system of male and female worms, S1-IR was only observed around the ootype/Mehlis' gland complex in the female. Immunostaining was also evident in the nervous system of both miracidium and cercarial larval stages. A post-embedding, IgG-conjugated colloidal gold immunostaining technique was employed to examine the subcellular distribution of SALMFamide-IR in the CNS of S. mansoni. Gold labelling of peptide was localized over dense-cored vesicles within nerve cell bodies and fibres constituting the neuropile of the anterior ganglia, cerebral commissure and nerve cords of the CNS. Antigen pre-absorption studies indicated that the results obtained do suggest S1-like immunostaining and not cross-reactivity with other peptides, in particular FMRFamide.