Efficient rate-power allocation for OFDM in a realistic fading environment

The implementation of practical adaptive resource allocation scheme remains a key criterion to be satisfied for realising spectrally efficient multitone wireless communications. The ever-increasing demand for spectrally efficient broadband wireless transmission technologies has spurred intensive research leading towards the implementation of adaptive OFDM and adaptive MIMO systems. Efforts in this direction have been frustrated however by the lack of a clear and accurate description of the fading behaviour typically encountered in the broadband wireless transmission environment. This has been partially been overcome by the use of mathematical modelling which captures certain large-scale characteristics of the channel and facilitates theoretical research. The “average” channel parameters gleaned from these processes is typically then used to inform the design and configuration of wireless networking equipment after the broad application of generous safety margins. The resulting solu�tion is therefore quite robust to certain transient channel quality degradation yet the generous safety tolerances render it unable to exploit other transient transmission quality improvements We seek to overcome the problems associated with this ap�proach by applying a theoretically sound novel adaptive resource allocation framework to actual broadband wireless channel development data. The allocation framework is derived from the optimal OFDM allocation scheme for a known channel [1]: the channel development data is obtained from actual measurement of a broadband wireless mobile environment [2]. Prediction tech�niques are employed to overcome the time lag between channel assessment and symbol transmission. We present the details of the predictive resource allocation scheme used and include a broad characterisation of the transmission environment in terms of the time-varying fading processes observed. We provide some results of the application of this scheme as typical performance levels that may be achieved in an actual transmission environment

Growth comparison of WtRv and AlRv on the basis of RLU and CFU counts.

<p><i>In vitro</i> (A), in lung homogenates from BALB/c mice after high-dose aerosol infections (implanting 4.05±0.11 and 4.44±0.05 log₁₀ CFU, respectively) (B) or low-dose infections (implanting 2.15±0.08 and 2.78±0.07 log₁₀ CFU, respectively) (C), and in live, anesthetized mice after high dose infection (D).</p

Serial, non-invasive, real-time assessment of vaccine efficacy in mice challenged with the AlRv strain of <i>M. tuberculosis</i>.

<p>(A) Mean RLU count (± S.D.) assessed in live, anesthetized mice vaccinated with either sham (S) or rBCG30 (V) vaccines followed by high-dose (hi), low-dose (lo) or no aerosol infection with the AlRv strain. (B) Mean CFU and RLU counts (± SD) from lung homogenates obtained 1, 17 and 27 days after challenge with the AlRv strain.</p

Serial, non-invasive, real-time assessment of anti-tuberculosis activity in infected mice.

<p>(A) Mean RLU count (± SD) assessed daily in live, anesthetized mice and normalized to the baseline RLU value. Mean (B) lung and (C) spleen CFU counts (± SD) at baseline and after 3 days of treatment. Abbreviations: KAN, kanamycin; STR, streptomycin; PZA, pyrazinamide; MFX, moxifloxacin; RIF, rifampin; EMB, ethambutol; LZD, linezolid; INH, isoniazid. Doses (in mg/kg): KAN 150; STR 150; PZA 150; MFX 200; RIF 40; EMB 200; LZD 200; INH 10.</p

Rapid, Serial, Non-invasive Assessment of Drug Efficacy in Mice with Autoluminescent<i>Mycobacterium ulcerans</i> Infection

<div><p>Background</p><p>Buruli ulcer (BU) caused by <i>Mycobacterium ulcerans</i> is the world's third most common mycobacterial infection. There is no vaccine against BU and surgery is needed for patients with large ulcers. Although recent experience indicates combination chemotherapy with streptomycin and rifampin improves cure rates, the utility of this regimen is limited by the 2-month duration of therapy, potential toxicity and required parenteral administration of streptomycin, and drug-drug interactions caused by rifampin. Discovery and development of drugs for BU is greatly hampered by the slow growth rate of <i>M. ulcerans</i>, requiring up to 3 months of incubation on solid media to produce colonies. Surrogate markers for evaluating antimicrobial activity in real-time which can be measured serially and non-invasively in infected footpads of live mice would accelerate pre-clinical evaluation of new drugs to treat BU. Previously, we developed bioluminescent <i>M. ulcerans</i> strains, demonstrating proof of concept for measuring luminescence as a surrogate marker for viable <i>M. ulcerans in vitro</i> and <i>in vivo</i>. However, the requirement of exogenous substrate limited the utility of such strains, especially for <i>in vivo</i> experiments.</p><p>Methodology/Principal Finding</p><p>For this study, we engineered <i>M. ulcerans</i> strains that express the entire <i>luxCDABE</i> operon and therefore are autoluminescent due to endogenous substrate production. The selected reporter strain displayed a growth rate and virulence similar to the wild-type parent strain and enabled rapid, real-time monitoring of <i>in vitro</i> and <i>in vivo</i> drug activity, including serial, non-invasive assessments in live mice, producing results which correlated closely with colony-forming unit (CFU) counts for a panel of drugs with various mechanisms of action.</p><p>Conclusions/Significance</p><p>Our results indicate that autoluminescent reporter strains of <i>M. ulcerans</i> are exceptional tools for pre-clinical evaluation of new drugs to treat BU due to their potential to drastically reduce the time, effort, animals, compound, and costs required to evaluate drug activity.</p></div

Footpad RLU and CFU values obtained from AlMu-infected mice treated from the day after infection.

<p>The mice were treated with RIF (red), STR (green) and CLR (blue) alone. Untreated (black). (A, D, G): RLU values obtained non-invasively from live mice (N = 8 on days 0–7; N = 4 on days 9–14); (B, E, H): RLU values obtained from footpad suspensions (N = 4 on days 7 and 14); (C, F, I): CFU values obtained from footpad suspensions (N = 4 on days 7 and 14). Values are mean ± SD.</p

Results of footpad RLU (A) and CFU (B) counts obtained during treatment in the murine model of <i>M. ulcerans</i> disease.

<p>Beginning 31 days post-infection, mice with a footpad lesion index ≥2 received no treatment (Ut, red for autoluminescent strain, black for wild type), CLR alone (blue) or STR+RIF (green) for 4 weeks. RLU counts (A) were determined non-invasively from footpads of live autoluminescent (AlMu)-infected mice (<i>in vivo</i>, solid lines) or from footpad suspensions of the same mice after sacrifice (<i>ex vivo</i>, broken lines). CFU counts (B) were determined from the same footpad suspensions (autoluminescent, triangles) and from those of wild-type (WtMu, squares)-infected mice.</p

RLU and CFU counts over time following mouse footpad infection with AlMu or WtMu strains.

<p>The background luminescence level of this method is 1.7 log₁₀ RLU/footpad. RLU-in vivo, light from live mice; RLU-ex vivo, light from footpad suspensions. Wild-type <i>M. ulcerans</i> (WtMu, black); autoluminescent <i>M. ulcerans</i> (AlMu, red). CFU results, solid lines and symbols; RLU results, broken lines and open symbols.</p

Comparison of MICs of selected antibiotics for autoluminescent <i>M. ulcerans</i> strain 1059 (AlMu) and its wild-type parent strain.

<p>Comparison of MICs of selected antibiotics for autoluminescent <i>M. ulcerans</i> strain 1059 (AlMu) and its wild-type parent strain.</p

Photograph of autoluminescent <i>M. ulcerans</i> colonies taken with a one-minute exposure time.

<p>Photograph of autoluminescent <i>M. ulcerans</i> colonies taken with a one-minute exposure time.</p