Cancer and systemic inflammation: treat the tumour and treat the host

Determinants of cancer progression and survival are multifactorial and host responses are increasingly appreciated to have a major role. Indeed, the development and maintenance of a systemic inflammatory response has been consistently observed to confer poorer outcome, in both early and advanced stage disease. For patients, cancer-associated symptoms are of particular importance resulting in a marked impact on day-to-day quality of life and are also associated with poorer outcome. These symptoms are now recognised to cluster with one another with anorexia, weight loss and physical function forming a recognised cluster whereas fatigue, pain and depression forming another. Importantly, it has become apparent that these symptom clusters are associated with presence of a systemic inflammatory response in the patient with cancer. Given the understanding of the above, there is now a need to intervene to moderate systemic inflammatory responses, where present. In this context the rationale for therapeutic intervention using nonselective anti-inflammatory agents is clear and compelling and likely to become a part of routine clinical practice in the near future. The published literature on therapeutic intervention using anti-inflammatory agents for cancer-associated symptoms was reviewed. There are important parallels with the development of useful treatments for the systemic inflammatory response in patients with rheumatological disease and cardiovascular disease

Optimal Receiver Antenna Location in Indoor Environment Using Dynamic Differential Evolution and Genetic Algorithm

[[abstract]]Using the impulse responses of these multipath channels, the bit error rate (BER) performance for binary pulse amplitude modulation impulse radio ultra-wideband communication system is calculated. The optimization location of receiving antenna is investigated by dynamic differential evolution (DDE) and genetic algorithm (GA) to minimize the outage probability. Numerical results show that the performance for reducing BER and outage probability by DDE algorithm is better than that by GA.[[notice]]補正完畢[[incitationindex]]SCI[[booktype]]紙本[[booktype]]電子

Diabetes causes marked inhibition of mitochondrial metabolism in pancreatic β-cells

Diabetes is a global health problem caused primarily by the inability of pancreatic β-cells to secrete adequate levels of insulin. The molecular mechanisms underlying the progressive failure of β-cells to respond to glucose in type-2 diabetes remain unresolved. Using a combination of transcriptomics and proteomics, we find significant dysregulation of major metabolic pathways in islets of diabetic βV59M mice, a non-obese, eulipidaemic diabetes model. Multiple genes/proteins involved in glycolysis/gluconeogenesis are upregulated, whereas those involved in oxidative phosphorylation are downregulated. In isolated islets, glucose-induced increases in NADH and ATP are impaired and both oxidative and glycolytic glucose metabolism are reduced. INS-1 β-cells cultured chronically at high glucose show similar changes in protein expression and reduced glucose-stimulated oxygen consumption: targeted metabolomics reveals impaired metabolism. These data indicate hyperglycaemia induces metabolic changes in β-cells that markedly reduce mitochondrial metabolism and ATP synthesis. We propose this underlies the progressive failure of β-cells in diabetes.Peer reviewe

The Effect of Transposable Element Insertions on Gene Expression Evolution in Rodents

Background:Many genomes contain a substantial number of transposable elements (TEs), a few of which are known to be involved in regulating gene expression. However, recent observations suggest that TEs may have played a very important role in the evolution of gene expression because many conserved non-genic sequences, some of which are know to be involved in gene regulation, resemble TEs. Results:Here we investigate whether new TE insertions affect gene expression profiles by testing whether gene expression divergence between mouse and rat is correlated to the numbers of new transposable elements inserted near genes. We show that expression divergence is significantly correlated to the number of new LTR and SINE elements, but not to the numbers of LINEs. We also show that expression divergence is not significantly correlated to the numbers of ancestral TEs in most cases, which suggests that the correlations between expression divergence and the numbers of new TEs are causal in nature. We quantify the effect and estimate that TE insertion has accounted for ~20% (95% confidence interval: 12% to 26%) of all expression profile divergence in rodents. Conclusions:We conclude that TE insertions may have had a major impact on the evolution of gene expression levels in rodents

Quantitative model for inferring dynamic regulation of the tumour suppressor gene p53

Background: The availability of various "omics" datasets creates a prospect of performing the study of genome-wide genetic regulatory networks. However, one of the major challenges of using mathematical models to infer genetic regulation from microarray datasets is the lack of information for protein concentrations and activities. Most of the previous researches were based on an assumption that the mRNA levels of a gene are consistent with its protein activities, though it is not always the case. Therefore, a more sophisticated modelling framework together with the corresponding inference methods is needed to accurately estimate genetic regulation from "omics" datasets. Results: This work developed a novel approach, which is based on a nonlinear mathematical model, to infer genetic regulation from microarray gene expression data. By using the p53 network as a test system, we used the nonlinear model to estimate the activities of transcription factor (TF) p53 from the expression levels of its target genes, and to identify the activation/inhibition status of p53 to its target genes. The predicted top 317 putative p53 target genes were supported by DNA sequence analysis. A comparison between our prediction and the other published predictions of p53 targets suggests that most of putative p53 targets may share a common depleted or enriched sequence signal on their upstream non-coding region. Conclusions: The proposed quantitative model can not only be used to infer the regulatory relationship between TF and its down-stream genes, but also be applied to estimate the protein activities of TF from the expression levels of its target genes

CdrS is a global transcriptional regulator influencing cell division in Haloferax volcanii

Cell division is a central mechanism of life and is essential for growth and development. Members of the Bacteria and Eukarya have different mechanisms for cell division, which have been studied in detail. </jats:p

Channel Characteristics of MIMO-WLAN Communications at 60GHz for Various Corridors

[[abstract]]A comparison of 4 × 4 multiple-input multiple-output wireless local area network wireless communication characteristics for six different geometrical shapes is investigated. These six shapes include the straight shape corridor with rectangular cross section, the straight shape corridor with arched cross section, the curved shape corridor with rectangular cross section, the curved shape corridor with arched cross section, the L-shape corridor, and the T-shape corridor. The impulse responses of these corridors are computed by applying shooting and bouncing ray/image (SBR/Image) techniques along with inverse Fourier transform. By using the impulse response of these multipath channels, the mean excess delay, root mean square (RMS) delay spread for these six corridors can be obtained. Numerical results show that the capacity for the rectangular cross section corridors is smaller than those for the arched cross section corridors regardless of the shapes. And the RMS delay spreads for the T-and the L-shape corridors are greater than the other corridors.[[notice]]補正完畢[[incitationindex]]SCI[[incitationindex]]EI[[booktype]]紙本[[booktype]]電子

The association between alcohol exposure and self-reported health status: The effect of separating former and current drinkers

Aims: To investigate the direction and degree of potential bias introduced to analyses of drinking and health status which exclude former drinkers from exposure groups. Design: Pooled analysis of 14 waves (1997–2010) of the U.S. National Health Interview Survey (NHIS). Setting: General population-based study. Participants: 404,462 participants, from 14 waves of the NHIS, who had known self-reported health status and alcohol consumption status. Measurements: Self-reported health status was used as the indicator of health. Two approaches were used to classify alcohol consumption: (i) separation of former drinkers and current drinkers, and (ii) combined former and current drinkers. The prevalence of fair/ poor health by alcohol use, gender and age with 95% confidence intervals was estimated. The difference in prevalence of fair/ poor health status for lifetime abstainers, former drinkers, current drinkers and drinkers (former drinkers and current drinkers combined) were compared using Poisson regression with robust estimations of variance. Findings: Excluding former drinkers from drinker groups exaggerates the difference in health status between abstainers and drinkers, especially for males. Conclusions: In cohort study analyses, former drinkers should be assigned to a drinking category based on their previous alcohol consumption patterns and not treated as a discrete exposure group

Giant cell tumor of the temporal bone – a case report

BACKGROUND: Giant cell tumor is a benign but locally aggressive bone neoplasm which uncommonly involves the skull. The petrous portion of the temporal bone forms a rare location for this tumor. CASE PRESENTATION: The authors report a case of a large giant cell tumor involving the petrous and squamous portions of the temporal bone in a 26 year old male patient. He presented with right side severe hearing loss and facial paresis. Radical excision of the tumor was achieved but facial palsy could not be avoided. CONCLUSION: Radical excision of skull base giant cell tumor may be hazardous but if achieved is the optimal treatment and may be curative

Evaluating Statistical Methods Using Plasmode Data Sets in the Age of Massive Public Databases: An Illustration Using False Discovery Rates

Plasmode is a term coined several years ago to describe data sets that are derived from real data but for which some truth is known. Omic techniques, most especially microarray and genomewide association studies, have catalyzed a new zeitgeist of data sharing that is making data and data sets publicly available on an unprecedented scale. Coupling such data resources with a science of plasmode use would allow statistical methodologists to vet proposed techniques empirically (as opposed to only theoretically) and with data that are by definition realistic and representative. We illustrate the technique of empirical statistics by consideration of a common task when analyzing high dimensional data: the simultaneous testing of hundreds or thousands of hypotheses to determine which, if any, show statistical significance warranting follow-on research. The now-common practice of multiple testing in high dimensional experiment (HDE) settings has generated new methods for detecting statistically significant results. Although such methods have heretofore been subject to comparative performance analysis using simulated data, simulating data that realistically reflect data from an actual HDE remains a challenge. We describe a simulation procedure using actual data from an HDE where some truth regarding parameters of interest is known. We use the procedure to compare estimates for the proportion of true null hypotheses, the false discovery rate (FDR), and a local version of FDR obtained from 15 different statistical methods