Multiplex primer extension analysis for rapid detection of major European mitochondrial haplogroups

The evolution of the human mitochondrial genome is reflected in the existence of eth- nically distinct lineages or haplogroups. Alterations of mitochondrial DNA (mtDNA) have been instrumental in studies of human phylogeny, in population genetics, and in molecular medicine to link pathological mutations to a variety of human diseases of complex etiology. For each of these applications, rapid and cost effective assays for mtDNA haplogrouping are invaluable. Here we describe a hierarchical system for mtDNA haplogrouping that combines multiplex PCR amplifications, multiplex single- base primer extensions, and CE for analyzing ten haplogroup-diagnostic mitochondrial single nucleotide polymorphisms. Using this rapid and cost-effective mtDNA geno- typing method, we were able to show that within a large, randomly selected cohort of healthy Austrians ( n = 1172), mtDNAs could be assigned to all nine major European haplogroups. Forty-four percent belonged to haplogroup H, the most frequent hap- logroup in European Caucasian populations. The other major haplogroups identified were U (15.4%), J (11.8%), T (8.2%) and K (5.1%). The frequencies of haplogroups in Austria is within the range observed for other European countries. Our method may be suitable for mitochondrial genotyping of samples from large-scale epidemiology stud- ies and for identifying markers of genetic susceptibility

Mitochondrial DNA mutations in renal cell carcinomas revealed no general impact on energy metabolism

Previously, renal cell carcinoma tissues were reported to display a marked reduction of components of the respiratory chain. To elucidate a possible relationship between tumourigenesis and alterations of oxidative phosphorylation, we screened for mutations of the mitochondrial DNA (mtDNA) in renal carcinoma tissues and patient-matched normal kidney cortex. Seven of the 15 samples investigated revealed at least one somatic heteroplasmic mutation as determined by denaturating HPLC analysis (DHPLC). No homoplasmic somatic mutations were observed. Actually, half of the mutations presented a level of heteroplasmy below 25%, which could be easily overlooked by automated sequence analysis. The somatic mutations included four known D-loop mutations, four so far unreported mutations in ribosomal genes, one synonymous change in the ND4 gene and four nonsynonymous base changes in the ND2, COI, ND5 and ND4L genes. One renal cell carcinoma tissue showed a somatic A3243G mutation, which is a known frequent cause of MELAS syndrome (mitochondrial encephalomyopathy, lactic acidosis, stroke-like episode) and specific compensatory alterations of enzyme activities of the respiratory chain in the tumour tissue. No difference between histopathology and clinical progression compared to the other tumour tissues was observed. In conclusion, the low abundance as well as the frequently observed low level of heteroplasmy of somatic mtDNA mutations indicates that the decreased aerobic energy capacity in tumour tissue seems to be mediated by a general nuclear regulated mechanism

Logical independence and quantum randomness

We propose a link between logical independence and quantum physics. We demonstrate that quantum systems in the eigenstates of Pauli group operators are capable of encoding mathematical axioms and show that Pauli group quantum measurements are capable of revealing whether or not a given proposition is logically dependent on the axiomatic system. Whenever a mathematical proposition is logically independent of the axioms encoded in the measured state, the measurement associated with the proposition gives random outcomes. This allows for an experimental test of logical independence. Conversely, it also allows for an explanation of the probabilities of random outcomes observed in Pauli group measurements from logical independence without invoking quantum theory. The axiomatic systems we study can be completed and are therefore not subject to Goedel's incompleteness theorem.Comment: 9 pages, 4 figures, published version plus additional experimental appendi

Identifying chromophore fingerprints of brain tumor tissue on hyperspectral imaging using principal component analysis

Hyperspectral imaging (HSI) is an optical technique that processes the electromagnetic spectrum at a multitude of monochromatic, adjacent frequency bands. The wide-bandwidth spectral signature of a target object's reflectance allows fingerprinting its physical, biochemical, and physiological properties. HSI has been applied for various applications, such as remote sensing and biological tissue analysis. Recently, HSI was also used to differentiate between healthy and pathological tissue under operative conditions in a surgery room on patients diagnosed with brain tumors. In this article, we perform a statistical analysis of the brain tumor patients' HSI scans from the HELICoiD dataset with the aim of identifying the correlation between reflectance spectra and absorption spectra of tissue chromophores. By using the principal component analysis (PCA), we determine the most relevant spectral features for intra- and inter-tissue class differentiation. Furthermore, we demonstrate that such spectral features are correlated with the spectra of cytochrome, i.e., the chromophore highly involved in (hyper) metabolic processes. Identifying such fingerprints of chromophores in reflectance spectra is a key step for automated molecular profiling and, eventually, expert-free biomarker discovery

Quantum models of classical mechanics: maximum entropy packets

In a previous paper, a project of constructing quantum models of classical properties has been started. The present paper concludes the project by turning to classical mechanics. The quantum states that maximize entropy for given averages and variances of coordinates and momenta are called ME packets. They generalize the Gaussian wave packets. A non-trivial extension of the partition-function method of probability calculus to quantum mechanics is given. Non-commutativity of quantum variables limits its usefulness. Still, the general form of the state operators of ME packets is obtained with its help. The diagonal representation of the operators is found. A general way of calculating averages that can replace the partition function method is described. Classical mechanics is reinterpreted as a statistical theory. Classical trajectories are replaced by classical ME packets. Quantum states approximate classical ones if the product of the coordinate and momentum variances is much larger than Planck constant. Thus, ME packets with large variances follow their classical counterparts better than Gaussian wave packets.Comment: 26 pages, no figure. Introduction and the section on classical limit are extended, new references added. Definitive version accepted by Found. Phy