Putrescine Reduces Antibiotic-Induced Oxidative Stress as a Mechanism of Modulation of Antibiotic Resistance in Burkholderia cenocepacia

Communication of antibiotic resistance among bacteria via small molecules is implicated in transient reduction of bacterial susceptibility to antibiotics, which could lead to therapeutic failures aggravating the problem of antibiotic resistance. Released putrescine from the extremely antibiotic resistant bacterium Burkholderia cenocepacia protects less resistant cells from different species against the antimicrobial peptide polymyxin B (PmB). Exposure of B. cenocepacia to sub-lethal concentrations of PmB and other bactericidal antibiotics induce reactive oxygen species (ROS) production and expression of the oxidative stress response regulator OxyR. We evaluated whether putrescine alleviates antibiotic-induced oxidative stress. The accumulation of intracellular ROS such as superoxide ion and hydrogen peroxide was assessed fluorometrically with dichlorofluorescein diacetate, while the expression of OxyR and putrescine synthesis enzymes was determined in luciferase assays using chromosomal promoter-lux reporter system fusions. We evaluated wild type and isogenic deletion mutant strains with defects in putrescine biosynthesis after exposure to sub-lethal concentrations of PmB and other bactericidal antibiotics. Exogenous putrescine protected against oxidative stress induced by PmB and other antibiotics, whereas reduced putrescine synthesis resulted in increased ROS generation, and a parallel increased sensitivity to PmB. Of the 3 B. cenocepacia putrescine synthesizing enzymes, PmB induced only BCAL2641, an ornithine decarboxylase. This study exposes BCAL2641 as a critical component of the putrescine-mediated communication of antibiotic resistance, and as a plausible target for designing inhibitors that would block the communication of such resistance among different bacteria, ultimately reducing the window of therapeutic failure in treating bacterial infections.

Cationicity-Enhanced Analogues of the Antimicrobial Peptides, AcrAP1 and AcrAP2, from the Venom of the Scorpion, Androctonus crassicauda, Display Potent Growth Modulation Effects on Human Cancer Cell Lines

The non disulphide-bridged peptides (NDBPs) of scorpion venoms are attracting increased interest due to their structural heterogeneity and broad spectrum of biological activities. Here, two novel peptides, named AcrAP1 and AcrAP2, have been identified in the lyophilised venom of the Arabian scorpion, Androctonus crassicauda, through “shotgun” molecular cloning of their biosynthetic precursor-encoding cDNAs. The respective mature peptides, predicted from these cloned cDNAs, were subsequently isolated from the same venom sample using reverse phase HPLC and their identities were confirmed by use of mass spectrometric techniques. Both were found to belong to a family of highly-conserved scorpion venom antimicrobial peptides - a finding confirmed through the biological investigation of synthetic replicates. Analogues of both peptides designed for enhanced cationicity, displayed enhanced potency and spectra of antimicrobial activity but, unlike the native peptides, these also displayed potent growth modulation effects on a range of human cancer cell lines. Thus natural peptide templates from venom peptidomes can provide the basis for rational analogue design to improve both biological potency and spectrum of action. The diversity of such templates from such natural sources undoubtedly provides the pharmaceutical industry with unique lead compounds for drug discovery.

Design methodology for low power and arametric robustness through output-quality modulation:Application to color-interpolation filtering

Power dissipation and robustness to process variation have conflicting design requirements. Scaling of voltage is associated with larger variations, while Vdd upscaling or transistor upsizing for parametric-delay variation tolerance can be detrimental for power dissipation. However, for a class of signal-processing systems, effective tradeoff can be achieved between Vdd scaling, variation tolerance, and output quality. In this paper, we develop a novel low-power variation-tolerant algorithm/architecture for color interpolation that allows a graceful degradation in the peak-signal-to-noise ratio (PSNR) under aggressive voltage scaling as well as extreme process variations. This feature is achieved by exploiting the fact that all computations used in interpolating the pixel values do not equally contribute to PSNR improvement. In the presence of Vdd scaling and process variations, the architecture ensures that only the less important computations are affected by delay failures. We also propose a different sliding-window size than the conventional one to improve interpolation performance by a factor of two with negligible overhead. Simulation results show that, even at a scaled voltage of 77% of nominal value, our design provides reasonable image PSNR with 40% power savings. © 2006 IEEE.

Directional Modulation Enhanced Retrodirective Array

Unlike the mathematical techniques adopted in classical cryptographic technology at higher protocol layers, it is shown that characteristics intrinsic to the physical layer can be exploited to secure useful information. It is shown that a retrodirective array can be made to operate more securely by incorporating directional modulation (DM) concepts. The presented new approach allows DM to operate in a multipath environment. Previously, DM systems could only operate in free space.

Directional Modulation Far-field Pattern Separation Synthesis Approach

In this study, a far-field power pattern separation approach is proposed for the synthesis of directional modulation (DM) transmitter arrays. Separation into information patterns and interference patterns is enabled by far-field pattern null steering. Compared with other DM synthesis methods, for example, bit error rate-driven DM optimisation and orthogonal vector injection, the approach developed in this study facilitates manipulation of artificial interference spatial distributions. With such capability more interference power can be projected into those spatial directions most vulnerable to eavesdropping, that is, the information side lobes. In such a fashion, information leaked through radiation side lobes can be effectively mitigated in a transmitter power efficient manner. Furthermore, for the first time, the authors demonstrate how multi-beam DM transmitters can be synthesised via this approach.

Constraining Directional Modulation Transmitter Radiation Patterns

An iterative pattern synthesis approach for directional modulation (DM) transmitters is presented in this study. Unlike all previous work, this study offers the first discussion on constraining DM transmitter far-field radiation patterns so that energy is primarily concentrated in the spatial direction where low bit error rate is to be achieved, while interference projected along other directions is reduced.

BRCA1, FANCD2 and Chk1 are potential molecular targets for the modulation of a radiation-induced DNA damage response in bystander cells

Radiotherapy is an important treatment option for many human cancers. Current research is investigating the use of molecular targeted drugs in order to improve responses to radiotherapy in various cancers. The cellular response to irradiation is driven by both direct DNA damage in the targeted cell and intercellular signalling leading to a broad range of bystander effects. This study aims to elucidate radiation-induced DNA damage response signalling in bystander cells and to identify potential molecular targets to modulate the radiation induced bystander response in a therapeutic setting. Stalled replication forks in T98G bystander cells were visualised via bromodeoxyuridine (BrdU) nuclear foci detection at sites of single stranded DNA. γH2AX co-localised with these BrdU foci. BRCA1 and FANCD2 foci formed in T98G bystander cells. Using ATR mutant F02-98 hTERT and ATM deficient GM05849 fibroblasts it could be shown that ATR but not ATM was required for the recruitment of FANCD2 to sites of replication associated DNA damage in bystander cells whereas BRCA1 bystander foci were ATM-dependent. Phospho-Chk1 foci formation was observed in T98G bystander cells. Clonogenic survival assays showed moderate radiosensitisation of directly irradiated cells by the Chk1 inhibitor UCN-01 but increased radioresistance of bystander cells. This study identifies BRCA1, FANCD2 and Chk1 as potential targets for the modulation of radiation response in bystander cells. It adds to our understanding of the key molecular events propagating out-of-field effects of radiation and provides a rationale for the development of novel molecular targeted drugs for radiotherapy optimisation.

Different frequencies of acupuncture for treatment for chronic low back pain: an-assessor blinded pilot randomised controlled trial.

OBJECTIVES:
To examine the feasibility of a main RCT to compare the effectiveness of two frequencies (2 versus 5 times/week) of acupuncture treatment for chronic low back pain (LBP).
METHODS:
Participants (n=30) with chronic LBP were randomised into two groups to receive 10 acupuncture treatments: Low Frequency Group, 2 times/week for five weeks (n=15); High Frequency Group, 5 times/week for two weeks (n=15). The following outcomes were measured blindly at baseline, 2 weeks, 5 weeks, 3 months and 1 year: pain on a VAS, functional disability using the RMDQ, quality of life using the Measure Yourself Medical Outcome Profile (MYMOP-2), psychological impact with the Coping Strategies Questionnaire (CSQ) and Pain Locus of Control (PLC) questionnaire. Two objective outcomes, the Shuttle Walk Test (SWT) and Lateral Trunk Flexibility (LTF), were also measured.
RESULTS:
The compliance rate was 100% for each group. Some of the measurements were shown to be sensitive (VAS, RMDQ, MYMOP-2 Wellbeing). 66-330 participants would be required for a fully powered non-inferiority trial. The groups were balanced at baseline for LBP and demographic characteristics. There were no significant differences between the groups in terms of any of the outcomes, at each follow-up time point. It was notable however that the clinically important improvement in terms of pain, functional disability, quality of life, and SWT in both groups was achieved within the first two weeks, which was maintained at one year follow-up.
CONCLUSIONS:
It is feasible to conduct a main RCT, to compare different frequencies of acupuncture for LBP, using sensitive measurements. Also the trend for early clinically important improvement within a minimum of four measurements is worthy of further study.

Improved Physical Layer Secure Wireless Communications using a Directional Modulation Enhanced Retrodirective Array

Unlike the mathematical encryption and decryption adopted in the classical cryptographic technology at the higher protocol layers, it is shown that characteristics intrinsic to the physical layer, such as wireless channel propagation, can be exploited to lock useful information. This information then can be automatically unlocked using real time analog RF means. In this paper retrodirective array, RDA, technology for spatial encryption in the multipath environment is for the first time combined with the directional modulation, DM, method normally associated with free space secure physical layer communications. We show that the RDA can be made to operate more securely by borrowing DM concepts and that the DM enhanced RDA arrangement is suitable for use in a multipath environment.

Compressive Sensing based Detector for Sparse Signal Modulation in Precoded OFDM

In this paper, we propose a sparse signal modulation (SSM) method for precoded orthogonal frequency division multiplexing (OFDM) systems and study the signal detection. Although a receiver is able to exploit a path diversity gain with random precoding in OFDM, the complexity of the receiver is usually high as the orthogonality is not retained due to precoding. However, with SSM, we can derive a low-complexity detector that can provide reasonably good performances with a low sparsity ratio based on the notion of compressive sensing (CS). An important feature of a CS detector is that it can estimate SSM signals with a small fraction of the received signals over sub-carriers. This feature can allow us to build a low cost receiver with a small number of demodulators.

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.

Fourier Rotman Lens Enabled Directional Modulation Transmitter

A 10 GHz Fourier Rotman lens enabled dynamic directional modulation (DM) transmitter is experimentally evaluated. Bit error rate (BER) performance is obtained via real-time data transmission. It is shown that Fourier Rotman DM functionality enhances system security performance in terms of narrower decodable low BER region and higher BER values associated with BER sidelobes especially under high signal to noise ratio (SNR) scenarios. This enhancement is achieved by controlled corruption of constellation diagrams in IQ space by orthogonal injection of interference. Furthermore, the paper gives the first report of a functional dual-beam DM transmitter, which has the capability of simultaneously projecting two independent data streams into two different spatial directions while simultaneously scrambling the information signals along all other directions.

Modulation Insensitive PLL for Tracking Antenna Applications

This article shows practical results of a self-tracking receiving antenna array using a new phase locked loop (PLL) tracking configuration. The PLL configuration differs from other architectures, as it has the new feature of being able to directly track phase modulated signals without requiring an additional unmodulated pilot carrier to be present. The PLLs are used within the antenna array to produce a constant phase intermediate frequency (IF) for each antenna element. These IF's can then be combined in phase, regardless of the angle of arrival of the signal, thus utilizing the antennas array factor. The article's main focus is on the phase jitter performance of the modulation insensitive PLL carrier recovery when tracking phase modulated signals of low signal to noise ratio. From this analysis, it is concluded that the new architecture, when optimally designed, can produce phase jitter performance close to that of a conventional tracking PLL.