Mesenchymal stem cells enhance survival and bacterial clearance in murine Escherichia coli pneumonia

Rationale: Bacterial pneumonia is the most common infectious cause of death worldwide and treatment is increasingly hampered by antibiotic resistance. Mesenchymal stem cells (MSCs) have been demonstrated to provide protection against acute inflammatory lung injury; however, their potential therapeutic role in the setting of bacterial pneumonia has not been well studied.

Objective: This study focused on testing the therapeutic and mechanistic effects of MSCs in a mouse model of Gram-negative pneumonia.

Methods and results: Syngeneic MSCs from wild-type mice were isolated and administered via the intratracheal route to mice 4 h after the mice were infected with Escherichia coli. 3T3 fibroblasts and phosphate-buffered saline (PBS) were used as controls for all in vivo experiments. Survival, lung injury, bacterial counts and indices of inflammation were measured in each treatment group. Treatment with wild-type MSCs improved 48 h survival (MSC, 55%; 3T3, 8%; PBS, 0%; p<0.05 for MSC vs 3T3 and PBS groups) and lung injury compared with control mice. In addition, wild-type MSCs enhanced bacterial clearance from the alveolar space as early as 4 h after administration, an effect that was not observed with the other treatment groups. The antibacterial effect with MSCs was due, in part, to their upregulation of the antibacterial protein lipocalin 2.

Conclusions: Treatment with MSCs enhanced survival and bacterial clearance in a mouse model of Gram-negative pneumonia. The bacterial clearance effect was due, in part, to the upregulation of lipocalin 2 production by MSCs

Antibacterial Effect of Human Mesenchymal Stem Cells is Mediated in Part from Secretion of the Antimicrobial Peptide LL-37

Recent in vivo studies indicate that mesenchymal stem cells (MSCs) may have beneficial effects in the treatment of sepsis induced by bacterial infection. Administration of MSCs in these studies improved survival and enhanced bacterial clearance. The primary objective of this study was to test the hypothesis that human MSCs possessed intrinsic antimicrobial properties. We studied the effect of human MSCs derived from bone marrow on the bacterial growth of Gram-negative (Escherichia coli and Pseudomonas aeruginosa) and Gram-positive (Staphylococcus aureus) bacteria. MSCs as well as their conditioned medium (CM) demonstrated marked inhibition of bacterial growth in comparison with control medium or normal human lung fibroblasts (NHLF). Analysis of expression of major antimicrobial peptides indicated that one of the factors responsible for the antimicrobial activity of MSC CM against Gram-negative bacteria was the human cathelicidin antimicrobial peptide, hCAP-18/LL-37. Both m-RNA and protein expression data showed that the expression of LL-37 in MSCs increased after bacterial challenge. Using an in vivo mouse model of E. coli pneumonia, intratracheal administration of MSCs reduced bacterial growth (in colony-forming unit) in the lung homogenates and in the bronchoalveolar lavage (BAL) fluid, and administration of MSCs simultaneously with a neutralizing antibody to LL-37 resulted in a decrease in bacterial clearance. In addition, the BAL itself from MSC-treated mice had a greater antimicrobial activity in comparison with the BAL of phosphate buffered saline (PBS)-treated mice. Human bone marrow-derived MSCs possess direct antimicrobial activity, which is mediated in part by the secretion of human cathelicidin hCAP-18/ LL-37.

Environmental tobacco smoke exposure and eye disease

Aim: To undertake a systematic review of the literature on the effect of environmental tobacco smoke (ETS) and eye disease. Methods: Medline (1950-January Week 2 2007), EMBASE (1980 to 2007 Week 07), SCOPUS and Science Direct were searched on ETS exposure and eye disease using various combinations of the following terms: passive smoking, environmental tobacco smoke, sidestream smoke, involuntary smoking, secondhand smoke; with eye, conjunctiva, sclera, episclera, cornea, lens, iris, retina, choroid, uvea, optic nerve, uveitis, iritis, blindness, visual loss, cataract, thyroid eye disease, conjunctivitis, age-related macular degeneration, dry eye, tears. The above terms were also used to search abstracts published on The Association for Research in Vision and Ophthalmology Annual Meeting abstracts, from 1995 to 2006, and the grey literature, including PhD and MSc theses/dissertations. A search was further conducted specifically on eye diseases where active smoking has been proposed to be a risk factor, including age-related macular degeneration, Graves ophthalmology, glaucoma, uveitis, refractive errors, strabismus, tobacco-alcohol amblyopia, non-arteritic ischaemic optic neuropathy, Leber optic neuropathy and diabetic retinopathy. Given the scarce number of studies found through the above search, all articles found on ETS and eye disease were included in this review. Results: Seven studies evaluated the possible relationship between ETS and an eye disease. These studies referred to refractive errors in children (n = 2), cataract (n = 1), age-related macular degeneration (n = 3) and Grave ophthalmopathy (n = 1). The data available were insufficient to establish conclusive relationships between ETS and these eye diseases. Conclusion: Very scarce data exist in the literature on the effect of ETS on diseases of the eye. It seems appropriate that ETS should be included in future studies addressing the effect of smoking on eye disease.

Proton ordering energetics in ice phases

Results from first-principles calculations on the subtle energetics of proton ordering in ice phases are shown only to depend on the electrostatic components of the total energy. Proton ordered ice phases can therefore be predicted using electronic structure methods or a tailored potential model. However, analysis of the electron density reveals that high order multipole components, up to hexadecapole, are needed to adequately capture total energy differences between proton ordered and disordered phases. This suggests that current potential models may be unable to reproduce the position of proton ordered ice phases in the phase diagram without extensions to describe high order electrostatics. (c) 2006 Elsevier B.V. All rights reserved.

Phase Equilibria of Binary and Ternary Systems Containing ILs, Dodecane, and Cyclohexanecarboxylic Acid

This paper reports both the binary and ternary phase behavior of ionic liquids for extracting cyclohexanecarboxylic acid (CCA) from dodecane. This system is a model for the extraction of acids representative of naphthenic acids found in crude oils. In order to develop an effective ternary liquid-liquid extraction system the preliminary selection of ionic liquids was based on CCA miscibility and the dodecane immiscibility with selected ILs. A wide range of ILs based on different cations, anions, cation alkyl-chain length, as well as the effect of temperature on the overall fluid phase behavior is reported. Factors such as variation of cation group, anion effect, alkyl-chain length, and temperature all impact the extraction to various degrees. The largest effects were found to be the lipophilicity of the IL cation and the co-ordination ability of the anion. While CCA capacity increased with lipophilicity of the cation, as did the dodecane. Highly coordinating anions such as trifluoroacetate and triflate demonstrated that highly efficient extraction could be obtained producing favorable tie-lines in the ternary phase diagram. Overall, this study demonstrates that ILs can selectively extract acids from hydrocarbon streams and offers possible treatment solutions for problems associated with the processing of high acid crude oils.

In vitro mesenchymal stem cell responses on laser-welded NiTi alloy

The biocompatibility of NiTi after laser welding was studied by examining the in vitro (mesenchymal stem cell) MSC responses at different sets of time varying from early (4 to 12 h) to intermediate phases (1 and 4 days) of cell culture. The effects of physical (surface roughness and topography) and chemical (surface Ti/Ni ratio) changes as a consequence of laser welding in different regions (WZ, HAZ, and BM) on the cell morphology and cell coverage were studied. The results in this research indicated that the morphology of MSCs was affected primarily by the topographical factors in the WZ: the well-defined and directional dendritic pattern and the presence of deeper grooves. The morphology of MSCs was not significantly modulated by surface roughness. Despite the possible initial Ni release in the medium during the cell culture, no toxic effect seemed to cause to MSCs as evidenced by the success of adhesion and spreading of the cells onto different regions in the laser weldment. The good biocompatibility of the NiTi laser weldment has been firstly reported in this study.

Effectiveness of the Construction Management Courses

This research assesses the effectiveness of current MSc. Construction Project Management programmes within the UK and Ireland. A review of published prospectuses is used to create questionnaires for universities, graduates and employers. Responses provide an insight into programme creation and their relative success in addressing the needs of industry and in achieving other educational objectives. Since the majority of learning institutions have attained professional accreditation, it is useful to review these awards and to assess their potential value to both graduates and industry alike. Interviews are conducted with representatives from the main professional accrediting bodies to understand their procedures and rigour in enforcing standards of education and training. The results show that project management education could be further enhanced by the inclusion of more practical learning and that current programmes place greater emphasis on hard skills at the expense of the softer human skills. There is clearly a need for a closer working relationship between academics and practitioners to tackle the perceived gap between theoretical learning and construction practice. Learning institutions can use the findings to improve their programmes and address the education deficiencies identified by the industry, by the professional institutions and by graduates.

Wear analysis and prediction of the life of a riveting die used in the automotive industry

Knowledge on the life span of the riveting dies used in the automotive industry is sparse. It is often the case that only when faulty products are produced are workers aware that their tool needs to be changed. This is of course costly both in terms of time and money. Responding to this challenge, this paper proposes a methodology which integrates wear and stress analysis to quantify the life of a riveting die. Experiments are carried out to measure the applied load required to split a rivet. The obtained results (i.e. force curves) are used to validate the wear mechanisms of the die observed using scanning electron microscopy. Sliding, impact, and adhesive wears are observed on the riveting die after a certain number of riveting cycles. The stress distribution on the die during riveting is simulated using a finite element (FE) approach. In order to confirm the accuracy of the FE model, the experimental force results are compared with the ones produced from FE simulation. The maximum and minimum von Mises' stresses generated from the FE model are input into a Goodman diagram and an S-N curve to compute the life of the riveting die. It is found that the riveting die is predicted to run for 4 980 000 cycles before failure.

The influence of the magnetic field on running penumbral waves in the solar chromosphere

We use images of high spatial and temporal resolution, obtained using both ground- and space-based instrumentation, to investigate the role magnetic field inclination angles play in the propagation characteristics of running penumbral waves in the solar chromosphere. Analysis of a near-circular sunspot, close to the center of the solar disk, reveals a smooth rise in oscillatory period as a function of distance from the umbral barycenter. However, in one directional quadrant, corresponding to the north direction, a pronounced kink in the period-distance diagram is found. Utilizing a combination of the inversion of magnetic Stokes vectors and force-free field extrapolations, we attribute this behavior to the cut-off frequency imposed by the magnetic field geometry in this location. A rapid, localized inclination of the magnetic field lines in the north direction results in a faster increase in the dominant periodicity due to an accelerated reduction in the cut-off frequency. For the first time, we reveal how the spatial distribution of dominant wave periods, obtained with one of the highest resolution solar instruments currently available, directly reflects the magnetic geometry of the underlying sunspot, thus opening up a wealth of possibilities in future magnetohydrodynamic seismology studies. In addition, the intrinsic relationships we find between the underlying magnetic field geometries connecting the photosphere to the chromosphere, and the characteristics of running penumbral waves observed in the upper chromosphere, directly supports the interpretation that running penumbral wave phenomena are the chromospheric signature of upwardly propagating magneto-acoustic waves generated in the photosphere.

Effect of laser treatment on the attachment and viability of mesenchymal stem cell responses on shape memory NiTi alloy

The objectives of this study were to investigate the effect of laser-induced surface features on the morphology, attachment and viability of mesenchymal stem cells (MSCs) at different periods of time, and to evaluate the biocompatibility of different zones: laser-melted zone (MZ), heat-affected zone (HAZ) and base metal (BM) in laser-treated NiTi alloy. The surface morphology and composition were studied by scanning electron microscope (SEM) and X-ray photoemission spectroscopy (XPS), respectively. The cell morphology was examined by SEM while the cell counting and viability measurements were done by haemocytometer and 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) colorimetric assay. The results indicated that the laser-induced surface features, such as surface roughening, presence of anisotropic dendritic pattern and complete surface Ni oxidation were beneficial to improve the biocompatibility of NiTi as evidenced by the highest cell attachment (4 days of culture) and viability (7 days of culture) found in the MZ. The biocompatibility of the MZ was the best, followed by the BM with the HAZ being the worst. The defective and porous oxide layer as well as the coarse grained structure might attribute to the inferior cell attachment (4 days of culture) and viability (7 days of culture) on the HAZ compared with the BM which has similar surface morphology.

Magma Evolution in the Primitive, Intra-oceanic Tonga Arc: Petrogenesis of Basaltic Andesites at Tofua Volcano

Tofua volcano is situated midway along the Tonga oceanic arc and has undergone two phases of ignimbrite-forming activity. The eruptive products are almost entirely basaltic andesites (52 center dot 5-57 wt % SiO2) with the exception of a volumetrically minor pre-caldera dacite. The suite displays a strong tholeiitic trend with K2O <1 wt %. Phenocryst assemblages typically comprise plagioclase + clinopyroxene +/- orthopyroxene with microlites of Ti-magnetite. Olivine (Fo(83-88)) is rare and believed to be dominantly antecrystic. An increase in the extent and frequency of reverse zoning in phenocrysts, sieve-textured plagioclase and the occurrence of antecrystic phases in post-caldera lavas record a shift to dynamic conditions, allowing the interaction of magma batches that were previously distinct. Pyroxene thermobarometry suggests crystallization at 950-1200 degrees C and 0 center dot 8-1 center dot 8 kbar. Volatile measurements of glassy melt inclusions indicate a maximum H2O content of 4 center dot 16 wt % H2O, and CO2-H2O saturation curves indicate that crystallization occurred at two levels, at depths of 4-5 center dot 5 km and 1 center dot 5-2 center dot 5 km. Major and trace element models suggest that the compositions of the majority of the samples represent a differentiation trend whereby the dacite was produced by 65% fractional crystallization of the most primitive basaltic andesite. Trace element models suggest that the sub-arc mantle source is the residuum of depleted Indian mid-ocean ridge basalt mantle (IDMM-1% melt), whereas radiogenic isotope data imply addition of 0 center dot 2% average Tongan sediment melt and a fluid component derived from the subducted altered Pacific oceanic crust. A horizontal array on the U-Th equiline diagram and Ra excesses of up to 500% suggest fluid addition to the mantle wedge within the last few thousand years. Time-integrated (Ra-226/Th-230) vs Sr/Th and Ba/Th fractionation models imply differentiation timescales of up to 4500 years for the dacitic magma compositions at Tofua.

Air-Sea Exchange of Legacy POPs in the North Sea Based on Results of Fate and Transport, and Shelf-Sea Hydrodynamic Ocean Models

The air-sea exchange of two legacy persistent organic pollutants (POPs), γ-HCH and PCB 153, in the North Sea, is presented and discussed using results of regional fate and transport and shelf-sea hydrodynamic ocean models for the period 1996–2005. Air-sea exchange occurs through gas exchange (deposition and volatilization), wet deposition and dry deposition. Atmospheric concentrations are interpolated into the model domain from results of the EMEP MSC-East multi-compartmental model (Gusev et al, 2009). The North Sea is net depositional for γ-HCH, and is dominated by gas deposition with notable seasonal variability and a downward trend over the 10 year period. Volatilization rates of γ-HCH are generally a factor of 2–3 less than gas deposition in winter, spring and summer but greater in autumn when the North Sea is net volatilizational. A downward trend in fugacity ratios is found, since gas deposition is decreasing faster than volatilization. The North Sea is net volatilizational for PCB 153, with highest rates of volatilization to deposition found in the areas surrounding polluted British and continental river sources. Large quantities of PCB 153 entering through rivers lead to very high local rates of volatilization.

The Influence of Structural Modeshape Variability on Limit Cycle Oscillation Behaviour

Modal analysis is a popular approach used in structural dynamic and aeroelastic problems due to its efficiency. The response of a structure is compo
sed of the sum of orthogonal eigenvectors or modeshapes and corresponding modal frequencies. This paper investigates the importance of modeshapes on the aeroelastic response of the Goland wing subject to structural uncertainties. The wing undergoes limit cycle oscillations (LCO) as a result of the inclusion of polynomial stiffness nonlinearities. The LCO computations are performed using a Harmonic Balance approach for speed, the modal properties of the system are extracted from MSC NASTRAN. Variability in both the wing’s structure and the store centre of gravity location is investigated in two cases:- supercritical and subcritical type LCOs. Results show that the LCO behaviour is only sensitive to change in modeshapes when the nature of the modes are changing significantly.

A high resolution study of complex organic molecules in hot cores

We present the results of a line identification analysis using data from the IRAM Plateau de Bure Inferferometer, focusing on six massive star-forming hot cores: G31.41+0.31, G29.96-0.02, G19.61-0.23, G10.62-0.38, G24.78+0.08A1 and G24.78+0.08A2. We identify several transitions of vibrationally excited methyl formate (HCOOCH$_3$) for the first time in these objects as well as transitions of other complex molecules, including ethyl cyanide (C$_2$H$_5$CN), and isocyanic acid (HNCO). We also postulate a detection of one transition of glycolaldehyde (CH$_2$(OH)CHO) in two new hot cores. We find G29.96-0.02, G19.61-0.23, G24.78+0.08A1 and 24.78+0.08A2 to be chemically very similar. G31.41+0.31, however, is chemically different: it manifests a larger chemical inventory and has significantly larger column densities. We suggest that it may represent a different evolutionary stage to the other hot cores in the sample, or it may surround a star with a higher mass. We derive column densities for methyl formate in G31.41+0.31, using the rotation diagram method, of $\times$10$^{17}$ cm$^{-2}$ and a T$_{rot}$ of $\sim$170 K. For G29.96-0.02, G24.78+0.08A1 and G24.78+0.08A2, glycolaldehyde, methyl formate and methyl cyanide all seem to trace the same material and peak at roughly the same position towards the dust emission peak. For G31.41+0.31, however, glycolaldehyde shows a different distribution to methyl formate and methyl cyanide and seems to trace the densest, most compact inner part of hot cores.

A static test method to assess swivel seat strength in frontal impact

Mechanical swivel seat adaptations are a key aftermarket disability modification to any small-to medium-sized passenger vehicle. However, the crashworthiness of these devices is currently unregulated and the existing 20g dynamic sled testing approach is prohibitively expensive for prototype assessment purposes. In this paper, an alternative quasi-static test method for swivel seat assessment is presented, and two different approaches (free-body diagram and multibody modelling) validated through published experimental data are developed to determine the appropriate loading conditions to apply in the quasi-static testing.Results show the two theoretical approaches can give similar results for estimating the quasi-static loading conditions, and this depends on the seatbelt configuration. Application of the approach to quasi-static testing of both conventional seats and those with integrated seat belts showed the approach to be successful and easy to apply. It is proposed that this method be used by swivel seat designers to assess new prototypes prior to final validation via the traditional 20g sled test.