Topoisomerase expression and amplification in solid tumours: Analysis of 24,262 patients.

BackgroundTopoisomerase I (TOPO1) and topoisomerase IIα (TOP2A) are specific targets of multiple chemotherapy drugs. Increased expression of TOPO1 protein and amplification of the TOP2A gene have been associated with treatment response in colorectal and breast cancers, respectively. TOPO1 and TOP2A may be potential therapeutic targets in other malignancies as well.Summary of methodsWe analysed TOPO1 protein expression and TOP2A gene amplification in patients (n = 24,262 specimens) with diverse cancers. Since HER2 and TOP2A co-amplification have been investigated for predictive value regarding anthracycline benefit, we analysed specimens for HER2 amplification as well.ResultsOverexpressed TOPO1 protein was present in 51% of the tumours. Four percent of the tumours had TOP2A amplification, with gallbladder tumours and gastroesophageal/oesophageal tumours having rates over 10%. Overall, 4903 specimens were assessed for both TOP2A and HER2 amplification; 129 (2.6%) had co-amplification. High rates (>40%) of HER2 amplification were seen in patients with TOP2A amplification in breast, ovarian, gastroesophageal/oesophageal and pancreatic cancer.ConclusionOur data indicate that increased TOPO1 expression and TOP2A amplification, as well as HER2 co-alterations, are present in multiple malignancies. The implications of these observations regarding sensitivity to chemotherapy not traditionally administered to these tumour types merits investigation

State Amplification

We consider the problem of transmitting data at rate R over a state dependent channel p(y|x,s) with the state information available at the sender and at the same time conveying the information about the channel state itself to the receiver. The amount of state information that can be learned at the receiver is captured by the mutual information I(S^n; Y^n) between the state sequence S^n and the channel output Y^n. The optimal tradeoff is characterized between the information transmission rate R and the state uncertainty reduction rate \Delta, when the state information is either causally or noncausally available at the sender. This result is closely related and in a sense dual to a recent study by Merhav and Shamai, which solves the problem of masking the state information from the receiver rather than conveying it.Comment: 9 pages, 4 figures, submitted to IEEE Trans. Inform. Theory, revise

Truly noiseless probabilistic amplification

Most of the schemes for "noiseless" amplification of coherent states, which have recently been attracting theoretical and experimental interest, share a common trait: The amplification is not truly noiseless, or perfect, for nonzero success probability. While this must hold true for all phase-independent amplification schemes, in this work we point out that truly noiseless amplification is indeed possible, provided that the states which we wish to amplify come from a finite set. Perfect amplification with unlimited average gain is then possible with finite success probability, for example, using techniques for unambiguously distinguishing between quantum states. Such realizations require only linear optics, no single-photon sources, and no photon counting. We also investigate the optimal success probability of perfect amplification of a symmetric set of coherent states. There are two regimes: low-amplitude amplification, where the target amplitude is below one, and general amplification. For the low-amplitude regime, analytic results for the optimal amplification success probabilities can be obtained. In this case a natural bound imposed by the ratio of success probabilities of optimal unambiguous discrimination of the source and amplified states can always be reached. We also show that for general amplification this bound cannot always be satisfied.</p

Alpha Channeling with High-field Launch of Lower Hybrid Waves

Although lower hybrid waves are effective at driving currents in present-day tokamaks, they are expected to interact strongly with high-energy particles in extrapolating to reactors. In the presence of a radial alpha particle birth gradient, this interaction can take the form of wave amplification rather than damping. While it is known that this amplification more easily occurs when launching from the tokamak high-field side, the extent of this amplification has not been made quantitative. Here, by tracing rays launched from the high- field-side of a tokamak, the required radial gradients to achieve amplification are calculated for a temperature and density regime consistent with a hot-ion-mode fusion reactor. These simulations, while valid only in the linear regime of wave amplification, nonetheless illustrate the possibilities for wave amplification using high-field launch of the lower hybrid wave.Comment: 7 pages, 7 figure

Single cell transcriptome analysis using next generation sequencing.

The heterogeneity of tissues, especially in cancer research, is a central issue in transcriptome analysis. In recent years, research has primarily focused on the development of methods for single cell analysis. Single cell analysis aims at gaining (novel) insights into biological processes of healthy and diseased cells. Some of the challenges in transcriptome analysis concern low abundance of sample starting material, necessary sample amplification steps and subsequent analysis. In this study, two fundamentally different approaches to amplification were compared using next-generation sequencing analysis: I. exponential amplification using polymerase-chain-reaction (PCR) and II. linear amplification. For both approaches, protocols for single cell extraction, cell lysis, cDNA synthesis, cDNA amplification and preparation of next-generation sequencing libraries were developed. We could successfully show that transcriptome analysis of low numbers of cells is feasible with both exponential and linear amplification. Using exponential amplification, the highest amplification rates up to 106 were possible. The reproducibility of results is a strength of the linear amplification method. The analysis of next generation sequencing data in single cell samples showed detectable expression in at least 16.000 genes. The variance between samples results in a need to work with a greater amount of biological replicates. In summary it can be said that single cell transcriptome analysis with next generation sequencing is possible but improvements leading to a higher yield of transcriptome reads is required. In the near future by comparing single cancer cells with healthy ones for example, a basis for improved prognosis and diagnosis can be realised

High MYC mRNA expression is more clinically relevant than MYC DNA amplification in triple-negative breast cancer

DNA abnormalities are used in inclusion criteria of clinical trials for treatments with specific targeted molecules. MYC is one of the most powerful oncogenes and is known to be associated with triple-negative breast cancer (TNBC). Its DNA amplification is often part of the targeted DNA-sequencing panels under the assumption of reflecting upregulated signaling. However, it remains unclear if MYC DNA amplification is a surrogate of its upregulated signaling. Thus, we investigated the difference between MYC DNA amplification and mRNA high expression in TNBCs utilizing publicly available cohorts. MYC DNA amplified tumors were found to have various mRNA expression levels, suggesting that MYC DNA amplification does not always result in elevated MYC mRNA expression. Compared to other subtypes, both MYC DNA amplification and mRNA high expression were more frequent in the TNBCs. MYC mRNA high expression, but not DNA amplification, was significantly associated with worse overall survival in the TNBCs. The TNBCs with MYC mRNA high expression enriched MYC target genes, cell cycle related genes, and WNT/β-catenin gene sets, whereas none of them were enriched in MYC DNA amplified TNBCs. In conclusion, MYC mRNA high expression, but not DNA amplification, reflects not only its upregulated signaling pathway, but also clinical significance in TNBCs

Monte Carlo simulations of pulse propagation in massive multichannel optical fiber communication systems

We study the combined effect of delayed Raman response and bit pattern randomness on pulse propagation in massive multichannel optical fiber communication systems. The propagation is described by a perturbed stochastic nonlinear Schr\"odinger equation, which takes into account changes in pulse amplitude and frequency as well as emission of continuous radiation. We perform extensive numerical simulations with the model, and analyze the dynamics of the frequency moments, the bit-error-rate, and the mutual distribution of amplitude and position. The results of our numerical simulations are in good agreement with theoretical predictions based on the adiabatic perturbation approach.Comment: Submitted to Physical Review E. 8 pages, 5 figure