Limited utility of qPCR-based detection of tumor-specific circulating mRNAs in whole blood from clear cell renal cell carcinoma patients

BACKGROUND: RNA sequencing data is providing abundant information about the levels of dysregulation of genes in various tumors. These data, as well as data based on older microarray technologies have enabled the identification of many genes which are upregulated in clear cell renal cell carcinoma (ccRCC) compared to matched normal tissue. Here we use RNA sequencing data in order to construct a panel of highly overexpressed genes in ccRCC so as to evaluate their RNA levels in whole blood and determine any diagnostic potential of these levels for renal cell carcinoma patients. METHODS: A bioinformatics analysis with Python was performed using TCGA, GEO and other databases to identify genes which are upregulated in ccRCC while being absent in the blood of healthy individuals. Quantitative Real Time PCR (RT-qPCR) was subsequently used to measure the levels of candidate genes in whole blood (PAX gene) of 16 ccRCC patients versus 11 healthy individuals. PCR results were processed in qBase and GraphPadPrism and statistics was done with Mann-Whitney U test. RESULTS: While most analyzed genes were either undetectable or did not show any dysregulated expression, two genes, CDK18 and CCND1, were paradoxically downregulated in the blood of ccRCC patients compared to healthy controls. Furthermore, LOX showed a tendency towards upregulation in metastatic ccRCC samples compared to non-metastatic. CONCLUSIONS: This analysis illustrates the difficulty of detecting tumor regulated genes in blood and the possible influence of interference from expression in blood cells even for genes conditionally absent in normal blood. Testing in plasma samples indicated that tumor specific mRNAs were not detectable. While CDK18, CCND1 and LOX mRNAs might carry biomarker potential, this would require validation in an independent, larger patient cohort

Classical Coulomb three-body problem in collinear eZe configuration

Classical dynamics of two-electron atom and ions H$^{-}$, He, Li$^{+}$, Be$^{2+}$,... in collinear eZe configuration is investigated. It is revealed that the mass ratio $\xi$ between necleus and electron plays an important role for dynamical behaviour of these systems. With the aid of analytical tool and numeircal computation, it is shown that thanks to large mass ratio $\xi$, classical dynamics of these systems is fully chaotic, probably hyperbolic. Experimental manifestation of this finding is also proposed.Comment: Largely rewritten. 21 pages. All figures are available in http://ace.phys.h.kyoto-u.ac.jp/~sano/3-body/index.htm

Modifying the photodetachment near a metal surface by a weak electric field

We show the photodetachment cross sections of H near a metal surface can be modified using a weak static electric field. The modification is possible because the oscillatory part of the cross section near a metal surface is directly connected with the transit-time and the action of the detached-electron closed-orbit which can be changed systematically by varying the static electric field strength. Photodetachment cross sections for various photon energies and electric field values are calculated and displayed.Comment: 16 pages, 7 figure

Renormalization group scale-setting from the action - a road to modified gravity theories

The renormalization group (RG) corrected gravitational action in Einstein-Hilbert and other truncations is considered. The running scale of the renormalization group is treated as a scalar field at the level of the action and determined in a scale-setting procedure recently introduced by Koch and Ramirez for the Einstein-Hilbert truncation. The scale-setting procedure is elaborated for other truncations of the gravitational action and applied to several phenomenologically interesting cases. It is shown how the logarithmic dependence of the Newton's coupling on the RG scale leads to exponentially suppressed effective cosmological constant and how the scale-setting in particular RG corrected gravitational theories yields the effective $f(R)$ modified gravity theories with negative powers of the Ricci scalar $R$. The scale-setting at the level of the action at the non-gaussian fixed point in Einstein-Hilbert and more general truncations is shown to lead to universal effective action quadratic in Ricci tensor.Comment: v1: 15 pages; v2: shortened to 10 pages, main results unchanged, published in Class. Quant. Gra

Constraining Single-Field Inflation with MegaMapper

We forecast the constraints on single-field inflation from the bispectrum of future high-redshift surveys such as MegaMapper. Considering non-local primordial non-Gaussianity (NLPNG), we find that current methods will yield constraints of order $\sigma(f_{\rm NL}^{\rm eq})\approx 23$, $\sigma(f_{\rm NL}^{\rm orth})\approx 12$ in a joint power-spectrum and bispectrum analysis, varying both nuisance parameters and cosmology, including a conservative range of scales. Fixing cosmological parameters and quadratic bias parameter relations, the limits tighten significantly to $\sigma(f_{\rm NL}^{\rm eq})\approx 17$, $\sigma(f_{\rm NL}^{\rm orth})\approx 8$. These compare favorably with the forecasted bounds from CMB-S4: $\sigma(f_{\rm NL}^{\rm eq})\approx 21$, $\sigma(f_{\rm NL}^{\rm orth})\approx 9$, with a combined constraint of $\sigma(f_{\rm NL}^{\rm eq})\approx 14$, $\sigma(f_{\rm NL}^{\rm orth})\approx 7$; this weakens only slightly if one instead combines with data from the Simons Observatory. We additionally perform a range of Fisher analyses for the error, forecasting the dependence on nuisance parameter marginalization, scale cuts, and survey strategy. Lack of knowledge of bias and counterterm parameters is found to significantly limit the information content; this could be ameliorated by tight simulation-based priors on the nuisance parameters. The error-bars decrease significantly as the number of observed galaxies and survey depth is increased: as expected, deep dense surveys are the most constraining, though it will be difficult to reach $\sigma(f_{\rm NL})\approx 1$ with current methods. The NLPNG constraints will tighten further with improved theoretical models (incorporating higher-loop corrections), as well as the inclusion of additional higher-order statistics.Comment: 6 pages, 3 figures, submitted to Phys. Lett.