Warburg effect in tumor bearing dogs

Tal como em medicina humana, a frequência de cancros apresenta uma tendência crescente nos animais de companhia, e apesar dos recentes avanços no diagnóstico e tratamento, continua a ser uma das principais causas de morbilidade e mortalidade em cães e gatos. A descoberta de novos biomarcadores clinicamente úteis para triagem, diagnóstico, detecção precoce da progressão e prognóstico de doenças oncológicas, bem como a descrição de vias metabólicas que poderão ser potenciais alvos terapêuticos são de extrema importância em oncologia humana e veterinária. O efeito Warburg descreve a síntese de ATP por células tumorais através de uma via metabólica alternativa à fosforilação oxidativa, a glicólise aeróbica, mesmo em condições de normoxemia. A glicólise aeróbia poderá produzir alterações bioquímicas que podem ser utilizadas como biomarcadores clínicos. Na medicina humana, este fenómeno tem sido documentado em numerosos estudos em oncologia. No entanto, a informação relacionada com o efeito Warburg em oncologia veterinária é escassa. Por este motivo, este estudo visou investigar as alterações no metabolismo energético tumoral através do estudo das variações metabólicas associadas ao efeito Warburg, através da determinação da concentração sérica de glucose, fructosamina, lactato e lactato desidrogenase (LDH) em cães com diferentes neoplasias malignas. Foram avaliados neste estudo 36 cães diagnosticados com diferentes tumores malignos e em diferentes estadios clínicos (grupo de animais doentes) e 23 cães considerados saudáveis, que constituíram o grupo controlo. Os animais doentes apresentaram concentrações séricas de lactato e LDH significativamente superiores (P=0.009 e P=0.023, respetivamente), e de fructosamina significativamente inferiores aos animais do grupo controlo (P=0.007). As concentrações séricas de glucose foram também inferiores em cães com neoplasias do que nos cães saudáveis, mas as diferenças não foram significativas (P=0.174). Os cães doentes foram divididos em grupos de acordo com o tipo de tumor que apresentaram, nomeadamente nos grupos de cães com carcinoma (n=13), sarcoma (n=10), linfoma (n=8) e adenocarcinoma mamário (n=8). Não foram encontradas diferenças significativas nas concentrações séricas de glucose, fructosamina, lactato e lactato desidrogenase entre estes grupos, ou entre estes grupos e os animais saudáveis (P>0.05 em todos os casos). Os resultados obtidos neste estudo mostram a ocorrência de alterações metabólicas que poderão estar associadas ao efeito Warburg em cães com diferentes tumores malignos, sugerindo que a glicólise aeróbica pode estar implicada na carcinogénese de diferentes neoplasias caninas. Os resultados sugerem também que os metabolitos analisados, nomeadamente a fructosamina, o lactato e a LDH, poderão ser biomarcadores úteis na prática clínica para triagem, diagnóstico, detecção precoce da progressão e prognóstico de doenças oncológicas caninas. Sugerem ainda que as vias metabólicas implicadas no efeito Warburg poderão ser potenciais alvos terapêuticos de diferentes neoplasias caninas. No entanto, neste estudo foi analisado um grupo pequeno de animais, e com tumores diferentes e em diferentes estadios clínicos. Serão necessários estudos futuros, com um maior número de animais e com uma população mais homogénea, para avaliar a função biológica do efeito Warburg na carcinogénese e a sua aplicação clínica em cada tipo tumoral.As in human medicine, the frequency of cancer presents an increasing trend in companion animals, and despite recent advances in diagnosis and treatment, remains a major cause of morbidity and mortality in dogs and cats. The discovery of new clinically useful biomarkers for screening, diagnosis, early detection of progression and prognosis of oncological diseases, as well as the description of metabolic pathways that could be potential therapeutic targets are of extreme importance in human and veterinary oncology. The Warburg effect describes the synthesis of ATP by tumor cells through an alternative metabolic pathway to oxidative phosphorylation, the aerobic glycolysis, even under normoxemia conditions. Aerobic glycolysis may produce biochemical changes that can be used as clinical biomarkers. In human medicine, this phenomenon has been documented in numerous studies in oncology. However, information related to the Warburg effect in veterinary oncology is scarce. For this reason, this study aimed to investigate changes in tumor energy metabolism through the study of metabolic variations associated with the Warburg effect, by determining the serum concentration of glucose, fructosamine, lactate and lactate dehydrogenase (LDH) in dogs with different malignant neoplasms. In this study, 36 dogs diagnosed with different malignant tumors and in different clinical stages (group of diseased animals) and 23 dogs considered healthy, which constituted the control group, were evaluated. Diseased animals (n=36) had significantly higher serum lactate and LDH concentrations (P=0.009 and P=0.023, respectively), and significantly lower serum fructosamine than animals in the control group (P=0.007). Serum glucose concentrations were also lower in dogs with cancer than in healthy dogs, but the differences were not significant (P=0.174). The diseased dogs were divided into groups according to the type of tumor, namely in the groups of dogs with carcinoma (n=13), sarcoma (n=10), lymphoma (n=8) and mammary adenocarcinoma (n=8). No significant differences were found in the serum concentrations of glucose, fructosamine, lactate and LDH between these groups, or between these groups and healthy animals (P>0.05 in all cases). The results obtained in this study show the occurrence of metabolic alterations that may be associated with the Warburg effect in dogs with different malignant tumors, suggesting that aerobic glycolysis may be involved in the carcinogenesis of different canine neoplasms. The results also suggest that the analyzed metabolites, namely fructosamine, lactate and LDH, might be useful biomarkers in clinical practice for screening, diagnosis, early detection of progression and prognosis of canine oncological diseases. They also suggest that the metabolic pathways involved in the Warburg effect might be potential therapeutic targets for different canine neoplasms. However, this study analyzed a small group of animals, with different tumors and at different clinical stages. Future studies, with a greater number of animals and with a more homogeneous population, will be necessary to evaluate the biological role of the Warburg effect in carcinogenesis and its clinical application in specific tumor type

Quantum theory of spontaneous and stimulated emission of surface plasmons

We introduce a quantization scheme that can be applied to surface waves propagating along a plane interface. An important result is the derivation of the energy of the surface wave for dispersive non-lossy media without invoking any specific model for the dielectric constant. Working in Coulomb's gauge, we use a modal representation of the fields. Each mode can be associated with a quantum harmonic oscillator. We have applied the formalism to derive quantum-mechanically the spontaneous emission rate of surface plasmon by a two-level system. The result is in very good agreement with Green's tensor approach in the non-lossy case. Green's approach allows also to account for losses, so that the limitations of a quantum approach of surface plasmons are clearly defined. Finally, the issue of stimulated versus spontaneous emission has been addressed. Because of the increasing density of states near the asymptote of the dispersion relation, it is quantitatively shown that the stimulated emission probability is too small to obtain gain in this frequency region.Comment: 14 pages, 5 figures, submitted to Phys. Rev. B

Novel Bayesian methods on multivariate cointegrated time series.

Many economic time series exhibit random walk or trend dynamics and other persistent non-stationary behaviour (e.g. stock prices, exchange rates, unemployment rate and net trading). If a time series is not stationary, then any shock can be permanent and there is no tendency for its level to return to a constant mean over time; moreover, in the long run, the volatility of the process is expected to grow without bound, and the time series cannot be predicted based on historical observations. Cointegration allows the identification of economic integrated time series that exhibit similar dynamics in the long run and the estimation of their relationships, by exploiting the stationary linear combinations of these time series. This thesis proposes three Bayesian estimation methods of the well-known Vector Error Correction Model (VECM) about difference stationary time series in order to extract the long-run equilibrium relationships. Each method used in this thesis is implemented using Markov Chain Monte Carlo (MCMC) and illustrated on synthetic data, and then on real economic data sets. The first method consists of a static model, where we compare comovements between Eurozone economic time series comprising net trading, long-term interest rates and the harmonised unemployment rate. Primiceri (2005) established a time-varying model for the vector autoregressive model. Following Primiceri and the idea of the static model seen in the first method, we are constructing a time-varying model for our VECM, from which we extract information about the time-varying cointegration matrix, and more interestingly about its time-varying rank (i.e. the cointegration rank) and independent cointegration relationships. These two first methods are based on the singular value decomposition of the cointegration matrix from the error correction model and the so-called irrelevance criterion, a flexible thresholding approach to determine its rank. In these two methods, the joint estimation of the cointegration rank and the cointegration relationships is deducted from synthetic data sets before applying them to real data sets (European economies and major stock market exchange indices). The last main chapter of this thesis covers the use of a prior singular distribution on the long-run relationship matrix of the VECM given the cointegration rank. Based on the definition of the singular matrix normal distribution, we also learn about the space definition and the density of such a distribution. We also remind the singular Inverse-Wishart distribution and in our discussion, we eventually open the issues arising in implementing a dynamic model, by developing the idea of a singular Inverse-Wishart distribution on the variance covariance matrix of the transition equation (see Chapter 6)

Balanced homodyne detection in second-harmonic generation microscopy

We demonstrate the association of two-photon nonlinear microscopy with balanced homodyne detection for investigating second harmonic radiation properties at nanoscale dimensions. Variation of the relative phase between second-harmonic and fundamental beams is retrieved, as a function of the absolute orientation of the nonlinear emitters. Sensitivity down to approximately 3.2 photon/s in the spatio-temporal mode of the local oscillator is obtained. This value is high enough to efficiently detect the coherent second-harmonic emission from a single KTiOPO4 crystal of sub-wavelength size.Comment: 9 pages to appear in Applied Physics Letter

Non-Local Control of Single Surface Plasmon

Quantum entanglement is a stunning consequence of the superposition principle. This universal property of quantum systems has been intensively explored with photons, atoms, ions and electrons. Collective excitations such as surface plasmons exhibit quantum behaviors. For the first time, we report an experimental evidence of non-local control of single plasmon interferences through entanglement of a single plasmon with a single photon. We achieved photon-plasmon entanglement by converting one photon of an entangled photon pair into a surface plasmon. The plasmon is tested onto a plasmonic platform in a Mach-Zehnder interferometer. A projective measurement on the polarization of the photon allows the non-local control of the interference state of the plasmon. Entanglement between particles of various natures paves the way to the design of hybrid systems in quantum information networks.Comment: 6 pages, 3 figure