Fisher Renormalization for Logarithmic Corrections

For continuous phase transitions characterized by power-law divergences, Fisher renormalization prescribes how to obtain the critical exponents for a system under constraint from their ideal counterparts. In statistical mechanics, such ideal behaviour at phase transitions is frequently modified by multiplicative logarithmic corrections. Here, Fisher renormalization for the exponents of these logarithms is developed in a general manner. As for the leading exponents, Fisher renormalization at the logarithmic level is seen to be involutory and the renormalized exponents obey the same scaling relations as their ideal analogs. The scheme is tested in lattice animals and the Yang-Lee problem at their upper critical dimensions, where predictions for logarithmic corrections are made.Comment: 10 pages, no figures. Version 2 has added reference

Metabolomic Characterization of Ovarian Epithelial Carcinomas by HRMAS-NMR Spectroscopy

Objectives. The objectives of the present study are to determine if a metabolomic study by HRMAS-NMR can (i) discriminate between different histological types of epithelial ovarian carcinomas and healthy ovarian tissue, (ii) generate statistical models capable of classifying borderline tumors and (iii) establish a potential relationship with patient's survival or response to chemotherapy. Methods. 36 human epithelial ovarian tumor biopsies and 3 healthy ovarian tissues were studied using 1H HRMAS NMR spectroscopy and multivariate statistical analysis. Results. The results presented in this study demonstrate that the three histological types of epithelial ovarian carcinomas present an effective metabolic pattern difference. Furthermore, a metabolic signature specific of serous (N-acetyl-aspartate) and mucinous (N-acetyl-lysine) carcinomas was found. The statistical models generated in this study are able to predict borderline tumors characterized by an intermediate metabolic pattern similar to the normal ovarian tissue. Finally and importantly, the statistical model of serous carcinomas provided good predictions of both patient's survival rates and the patient's response to chemotherapy. Conclusions. Despite the small number of samples used in this study, the results indicate that metabolomic analysis of intact tissues by HRMAS-NMR is a promising technique which might be applicable to the therapeutic management of patients

Structure−Function Correlation of Chloroquine and Analogues as Transgene Expression Enhancers in Nonviral Gene Delivery

To understand how chloroquine (CQ) enhances transgene expression in polycation-based, nonviral gene delivery systems, a number of CQ analogues with variations in the aliphatic amino side chain or in the aromatic ring are synthesized and investigated. Our studies indicate that the aliphatic amino moiety of CQ is essential to provide increased gene expression. Further, the enhancements are more dramatically affected by changes to the aromatic ring and are positively correlated to the strength of intercalation between DNA and the CQ analogues. Quinacrine (QC), a CQ analogue with a fused acridinyl structure that can strongly intercalate DNA, enhances transfection similarly to CQ at a concentration 10 times lower, while N^4-(4-pyridinyl)-N^1,N^1-diethyl-1,4-pentanediamine (CP), a CQ analogue that has a weakly intercalating pyridinyl ring, shows no effect on gene expression. Subtle change on the 7-substituent of the chloroquine aromatic structure can also greatly affect the ability of the CQ analogues to enhance transgene expression. Transfection in the presence of N^4-(7-trifluoromethyl-4-quinolinyl)-N^1,N^1-diethyl-1,4-pentanediamin e (CQ7a) shows expression efficiency 10 times higher than in the presence of CQ at same concentration, while transfection in the presence of N^4-(4-quinolinyl)-N^1,N^1-diethyl-1,4-pentanediamine (CQ7b) does not reveal any enhancing effects on expression. Through a number of comparative studies with CQ and its analogues, we conclude that there are at least three mechanistic features of CQ that lead to the enhancement in gene expression:  (i) pH buffering in endocytic vesicles, (ii) displacement of polycations from the nucleic acids in polyplexes, and (iii) alteration of the biophysical properties of the released nucleic acid

Dynamic Fluctuation Phenomena in Double Membrane Films

Dynamics of double membrane films is investigated in the long-wavelength limit including the overdamped squeezing mode. We demonstrate that thermal fluctuations essentially modify the character of the mode due to its nonlinear coupling to the transversal shear hydrodynamic mode. The corresponding Green function acquires as a function of the frequency a cut along the imaginary semi-axis. Fluctuations lead to increasing the attenuation of the squeezing mode it becomes larger than the `bare' value.Comment: 7 pages, Revte

Mise à jour des recommandations du GEFPICS pour l’évaluation du statut HER2 dans les cancers du sein en France

En Europe, les patientes atteintes d’un cancer du sein invasif susceptibles de recevoir un traitement ciblé anti-HER2 sont actuellement sélectionnées sur la base d’un test immunohistochimique (IHC). Les techniques d’hybridation in situ (HIS) doivent être utilisées pour l’évaluation des cas IHC ambigus (2+) et pour l’étalonnage de la technique IHC. Les patientes éligibles au traitement ciblant HER2 présentent un statut HER2 positif défini par un test IHC 3+ ou un test 2+ amplifié. Une détection correcte du statut HER2 est indispensable à une utilisation optimale des thérapeutiques ciblées puisque leur efficacité est limitée aux patientes surexprimant HER2. Il est capital que l’évaluation du statut HER2 soit optimisée et fiable. Ces recommandations du groupe d’étude des facteurs pronostiques IHC dans le cancer du sein (GEFPICS) détaillent et commentent les différentes étapes des techniques IHC et HIS, les contrôles utilisables et les règles générales de l’apprentissage de la lecture. Une fois acquis, ce savoir-faire doit être pérennisé par l’observation de règles de bonnes pratiques techniques (utilisation rigoureuse de témoins internes et externes et participation régulière à des programmes d’Assurance qualité [AQ])., Summary In Europe, patients who may benefit from an HER2 targeted drug are currently selected by immunohistochemistry (IHC). In situ hybridization (ISH) techniques should be used for complementary assessment of ambiguous 2+ IHC cases and for the calibration of the IHC technique. Eligibility to an HER2 target treatment is defined by an HER2 positive status being IHC test 3+ or 2+ amplified. Reliable detection of HER2 status is essential to the appropriate usage of HER2 targeted drugs because its specificity is limited to tumors overexpressing HER2. It is essential that the IHC evaluation of the HER2 status of a mammary carcinoma is optimized and reliable. This GEFPICS’ guidelines look over the different steps of the IHC technique, the controls and, the rules for interpretation. Once acquired, this knowledge must be perpetuated by the observation of rules of good technical practice (internal and external controls, quality assurance programs)

Evolutionary genetics of MHC class II beta genes in the brown hare, Lepus europaeus

The genes of the major histocompatibility complex (MHC) are attractive candidates for investigating the link between adaptive variation and individual fitness. High levels of diversity at the MHC are thought to be the result of parasite-mediated selection and there is growing evidence to support this theory. Most studies, however, target just a single gene within the MHC and infer any evidence of selection to be representative of the entire gene region. Here we present data from three MHC class II beta genes (DPB, DQB, and DRB) for brown hares in two geographic regions and compare them against previous results from a class II alpha-chain gene (DQA). We report moderate levels of diversity and high levels of population differentiation in the DQB and DRB genes (Na = 11, Dest = 0.071 and Na = 15, Dest = 0.409, respectively), but not for the DPB gene (Na = 4, Dest = 0.00). We also detected evidence of positive selection within the peptide binding region of the DQB and DRB genes (95% CI, ω > 1.0) but found no signature of selection for DPB. Mutation and recombination were both found to be important processes shaping the evolution of the class II genes. Our findings suggest that while diversifying selection is a significant contributor to the generally high levels of MHC diversity, it does not act in a uniform manner across the entire MHC class II region. The beta-chain genes that we have characterized provide a valuable set of MHC class II markers for future studies of the evolution of adaptive variation in Leporids