Human mesenchymal stem cells reduce mortality and bacteremia in gram-negative sepsis in mice in part by enhancing the phagocytic activity of blood monocytes

The potential therapeutic value of cell-based therapy with mesenchymal stem cells (MSC) has been reported in mouse models of polymicrobial peritoneal sepsis. However, the mechanisms responsible for the beneficial effects of MSC have not been well defined. Therefore, we tested the therapeutic effect of intravenous bone marrow-derived human MSC in peritoneal sepsis induced by gram-negative bacteria. At 48 h, survival was significantly increased in mice treated with intravenous MSC compared with control mice treated with intravenous fibroblasts (3T3) or intravenous PBS. There were no significant differences in the levels of TNF-a, macrophage inflammatory protein 2, or IL-10 in the plasma. However, there was a marked reduction in the number of bacterial colony-forming units of Pseudomonas aeruginosa in the blood of MSC-treated mice compared with the 3T3 and PBS control groups. In addition, phagocytic activity was increased in blood monocytes isolated from mice treated with MSC compared with the 3T3 and PBS groups. Furthermore, levels of C5a anaphylotoxin were elevated in the blood of mice treated with MSC, a finding that was associated with upregulation of the phagocytosis receptor CD11b on monocytes. The phagocytic activity of neutrophils was not different among the groups. There was also an increase in alternately activated monocytes/macrophages (CD163- and CD206-positive) in the spleen of the MSC-treated mice compared with the two controls. Thus intravenous MSC increased survival from gram-negative peritoneal sepsis, in part by a monocyte-dependent increase in bacterial phagocytosis.

Quinolones sensitize gram-negative bacteria to antimicrobial peptides

The treatment of infections caused by bacteria resistant to the vast majority of antibiotics is a challenge worldwide. Antimicrobial peptides (APs) make up the front line of defense in those areas exposed to microorganisms, and there is intensive research to explore their use as new antibacterial agents. On the other hand, it is known that subinhibitory concentrations of antibiotics affect the expression of numerous bacterial traits. In this work we evaluated whether treatment of bacteria with subinhibitory concentrations of quinolones may alter the sensitivity to APs. A 1-h treatment of Klebsiella pneumoniae with 0.25 x the MIC of ciprofloxacin rendered bacteria more sensitive to polymyxins B and E, human neutrophil defensin 1, and beta-defensin 1. Levofloxacin and nalidixic acid at 0.25 x the MICs also increased the sensitivity of K. pneumoniae to polymyxin B, whereas gentamicin and ceftazidime at 0.25 x the MICs did not have such an effect. Ciprofloxacin also increased the sensitivities of K. pneumoniae ciprofloxacin-resistant strains to polymyxin B. Two other pathogens, Pseudomonas aeruginosa and Haemophilus influenzae, also became more sensitive to polymyxins B and E after treatment with 0.25 x the MIC of ciprofloxacin. Incubation with ciprofloxacin did not alter the expression of the K. pneumoniae loci involved in resistance to APs. A 1-N-phenyl-naphthylamine assay showed that ciprofloxacin and levofloxacin increased the permeabilities of the K. pneumoniae and P. aeruginosa outer membranes, while divalent cations antagonized this action. Finally, we demonstrated that ciprofloxacin and levofloxacin increased the binding of APs to the outer membrane by using dansylated polymyxin B.

Power Allocation Strategies across N Orthogonal Channels at Both Source and Relay

A wireless relay network with one source, one relay and one destination is considered, where nodes communicate via N orthogonal channels. We develop optimal power allocation strategies at both the source and relay for maximizing the overall source-destination capacity under individual power constraints at the source and relay. Some properties of the optimal solution are studied. © 2012 IEEE.

Comparison of adaptive beamforming and orthogonal STBC with outdated feedback

We compare the achievable performance of adaptive beamforming (A-BF) and adaptive orthogonal space time block coding (A-OSTBC) with outdated channel feedback. We extend our single user setup to multiuser diversity systems employing adaptive modulation, and illustrate the impact of feedback delay on the multiuser diversity gain with either A-OSTBC or A-BF. Using closed-form expressions for spectral efficiency and average BER of a multiuser diversity system derived in this paper, we prove that the A-BF scheme outperforms the A-OSTBC scheme with no feedback delay. However, when the feedback delay is large, the A-OSTBC scheme achieves better performance due to the reduced diversity advantage of A-BF. We observe that more transmit antennas bring higher spectral efficiency for BF. With small feedback delay, this becomes inverted using OSTBC, due to the effect of channel-hardening. Interestingly, however, we show that A-OSTBC with multiple users enjoys improved spectral efficiency when the number of transmit antennas is increased and the feedback delay is significant

Orthogonal space-time block coded rate-adaptive modulation with outdated feedbasck

Abstract-Channel state information (CSI) at the transmitter can be used to adapt transmission rate or antenna gains in multi-antenna systems. We propose a rate-adaptive M-QAM scheme equipped with orthogonal space-time block coding with simple outdated, finite-rate feedback over independent flat fading channels. We obtain closed-form expressions for the average BER and throughput for our scheme, and analyze the effects of possibly delayed feedback on the performance gains. We derive optimal switching thresholds maximizing the average throughput under average and outage BER constraints with outdated feedback. Our numerical results illustrate the immunity of our optimal thresholds to delayed feedback.

Power allocation strategies across N orthogonal channels for single-relay networks at both source and relay

We consider a wireless relay network with one source, one relay and one destination, where communications between nodes are preformed over N orthogonal channels. This, for example, is the case when orthogonal frequency division multiplexing is employed for data communications. Since the power available at the source and relay is limited, we study optimal power allocation strategies at the source and relay in order to maximize the overall source-destination capacity. Depending on the availability of the channel state information at both the source and relay or only at the relay, power allocation is performed at both the source and relay or only at the relay. Considering different setups for the problem, various optimization problems are formulated and solved. Some properties of the optimal solution are also proved.

Implementation of a non-orthogonal model for the finite element simulation of textile composite draping

In the pursuit of producing high quality, low-cost composite aircraft structures, out-of-autoclave manufacturing processes for textile reinforcements are being simulated with increasing accuracy. This paper focuses on the continuum-based, finite element modelling of textile composites as they deform during the draping process. A non-orthogonal constitutive model tracks yarn orientations within a material subroutine developed for Abaqus/Explicit, resulting in the realistic determination of fabric shearing and material draw-in. Supplementary material characterisation was experimentally performed in order to define the tensile and non-linear shear behaviour accurately. The validity of the finite element model has been studied through comparison with similar research in the field and the experimental lay-up of carbon fibre textile reinforcement over a tool with double curvature geometry, showing good agreement.

A markerless deletion method for genetic manipulation of Burkholderia cenocepacia and other multidrug-resistant gram-negative bacteria

Genetic manipulation of multidrug-resistant bacteria is often difficult and hinders progress in understanding their physiology and pathogenesis. This book chapter highlights advances in genetic manipulation of Burkholderia cenocepacia, which are also applicable to other members of the Burkholderia cepacia complex and multidrug-resistant gram-negative bacteria of other genera. The method detailed here is based on the I-SceI homing endonuclease system, which can be efficiently used for chromosomal integration, deletion, and genetic replacement. This system creates markerless mutations and insertions without leaving a genetic scar and thus can be reused successively to generate multiple modifications in the same strain.

Cough-generated aerosols of Pseudomonas aeruginosa and other Gram-negative bacteria from patients with cystic fibrosis

BACKGROUND: Pseudomonas aeruginosa is the most common bacterial pathogen in patients with cystic fibrosis (CF). Current infection control guidelines aim to prevent transmission via contact and respiratory droplet routes and do not consider the possibility of airborne transmission. It was hypothesised that subjects with CF produce viable respirable bacterial aerosols with coughing.

METHODS: A cross-sectional study was undertaken of 15 children and 13 adults with CF, 26 chronically infected with P aeruginosa. A cough aerosol sampling system enabled fractioning of respiratory particles of different sizes and culture of viable Gram-negative non-fermentative bacteria. Cough aerosols were collected during 5 min of voluntary coughing and during a sputum induction procedure when tolerated. Standardised quantitative culture and genotyping techniques were used.

RESULTS: P aeruginosa was isolated in cough aerosols of 25 subjects (89%), 22 of whom produced sputum samples. P aeruginosa from sputum and paired cough aerosols were indistinguishable by molecular typing. In four cases the same genotype was isolated from ambient room air. Approximately 70% of viable aerosols collected during voluntary coughing were of particles <or=3.3 microm aerodynamic diameter. P aeruginosa, Burkholderia cenocepacia, Stenotrophomonas maltophilia and Achromobacter xylosoxidans were cultivated from respiratory particles in this size range. Positive room air samples were associated with high total counts in cough aerosols (p = 0.003). The magnitude of cough aerosols was associated with higher forced expiratory volume in 1 s (r = 0.45, p = 0.02) and higher quantitative sputum culture results (r = 0.58, p = 0.008).

CONCLUSION: During coughing, patients with CF produce viable aerosols of P aeruginosa and other Gram-negative bacteria of respirable size range, suggesting the potential for airborne transmission.

Orthogonal Vector Approach for Synthesis of Multi-beam Directional Modulation Transmitters

An orthogonal vector approach is proposed for the synthesis of multi-beam directional modulation (DM) transmitters. These systems have the capability of concurrently projecting independent data streams into different specified spatial directions while simultaneously distorting signal constellations in all other directions. Simulated bit error rate (BER) spatial distributions are presented for various multi-beam system configurations in order to illustrate representative examples of physical layer security performance enhancement that can be achieved.