Slow magnetic dynamics and hysteresis loops of a bulk ferromagnet

Magnetic dynamics of a bulk ferromagnet, a new single crystalline compound Co7(TeO3)4Br6, was studied by ac susceptibility and the related techniques. Very large Arrhenius activation energy of 17.2 meV (201 K) and long attempt time (2x10^(-4)s) span the full spectrum of magnetic dynamics inside a convenient frequency window, offering a rare opportunity for general studies of magnetic dynamics. Within the experimental window the ac susceptibility data build almost ideally semicircular Cole-Cole plots. Comprehensive study of experimental dynamic hysteresis loops of the compound is presented and interpreted within a simple thermal-activation-assisted spin lattice relaxation model for spin reversal. Quantitative agreement between the experimental results and the model's prediction for dynamic coercive field is achieved by assuming the central physical quantity, the Debye relaxation rate, to depend on frequency, as well as on the applied field strength and sample temperature. Cross-over between minor- to major hysteresis loops is carefully analyzed. Low-frequency limitations of the model, relying on domain wall pinning effects, are experimentally detected and appropriately discussed.Comment: A paragraph on dynamical-hysteresis assymetry added, text partially revised; Accepted in Physical Review

Clinical and molecular characterization of HER2 amplified-pancreatic cancer

<p>Background: Pancreatic cancer is one of the most lethal and molecularly diverse malignancies. Repurposing of therapeutics that target specific molecular mechanisms in different disease types offers potential for rapid improvements in outcome. Although HER2 amplification occurs in pancreatic cancer, it is inadequately characterized to exploit the potential of anti-HER2 therapies.</p> <p>Methods: HER2 amplification was detected and further analyzed using multiple genomic sequencing approaches. Standardized reference laboratory assays defined HER2 amplification in a large cohort of patients (n = 469) with pancreatic ductal adenocarcinoma (PDAC).</p> <p>Results: An amplified inversion event (1 MB) was identified at the HER2 locus in a patient with PDAC. Using standardized laboratory assays, we established diagnostic criteria for HER2 amplification in PDAC, and observed a prevalence of 2%. Clinically, HER2- amplified PDAC was characterized by a lack of liver metastases, and a preponderance of lung and brain metastases. Excluding breast and gastric cancer, the incidence of HER2-amplified cancers in the USA is >22,000 per annum.</p> <p>Conclusions: HER2 amplification occurs in 2% of PDAC, and has distinct features with implications for clinical practice. The molecular heterogeneity of PDAC implies that even an incidence of 2% represents an attractive target for anti-HER2 therapies, as options for PDAC are limited. Recruiting patients based on HER2 amplification, rather than organ of origin, could make trials of anti-HER2 therapies feasible in less common cancer types.</p&gt

Surveillance sanitaire des cocoteraies adultes en Afrique de l'Ouest. I. Contrôles ordinaires

La plupart des ravageurs connus dans les cocoteraies d'Afrique de l'Ouest passent le plus souvent inaperçus, bien qu'ils soient toujours présents. Dans certaines conditions, difficiles à définir, il y a pullulation d'un ou de plusieurs d'entre eux et, en conséquence, des dégâts importants peuvent alors se produire. Des contrôles sanitaires fréquents sont nécessaires pour la conduite de la méthode de lutte intégrée, généralement adoptée à présent en défense des cultures, ce qui suppose une bonne connaissance des ravageurs, de leur biologie et de leurs ennemis naturels. Comme pour le palmier à huile, il y a deux types de contrôles phytosanitaires : - les contrôles ordinaires, décrits dans ces " Conseils ", qui permettent de suivre l'ensemble des populations de ravageurs, d'insectes auxiliaires, et de détecter toute anomalie susceptible de se traduire par des dégâts préjudiciables ; - les contrôles spéciaux, spécifiques d'un ravageur donné, qui feront l'objet d'une autre page de Pratique agricole (1 ), et sont réalisés sur un échantillon d'observation plus important. Ils permettent de suivre plus précisément l'évolution de ce ravageur, l'intensité et l'étendue des dégâts qu'il provoque. Toutefois, la décision d'intervention par traitement ne peut être prise à bon escient qu'après examen attentif des résultats d'un ou de plusieurs contrôles spéciaux réalisés après détection de l'attaque par un contrôle ordinaire. La présente " Page de pratique agricole " traite de la conduite des contrôles phytosanitaires en cocoteraie de plus de quatre ans, entrée en production. La surveillance des jeunes cocoteraies, beaucoup plus vulnérables, fera également l'objet d'autres " Conseils ". (Résumé d'auteur

Lack of correlation of stem cell markers in breast cancer stem cells

BACKGROUND: Various markers are used to identify the unique sub-population of breast cancer cells with stem cell properties. Whether these markers are expressed in all breast cancers, identify the same population of cells, or equate to therapeutic response is controversial. METHODS: We investigated the expression of multiple cancer stem cell markers in human breast cancer samples and cell lines in vitro and in vivo, comparing across and within samples and relating expression with growth and therapeutic response to doxorubicin, docetaxol and radiotherapy. RESULTS: CD24, CD44, ALDH and SOX2 expression, the ability to form mammospheres and side-population cells are variably present in human cancers and cell lines. Each marker identifies a unique rather than common population of cancer cells. In vivo, cells expressing these markers are not specifically localized to the presumptive stem cell niche at the tumour/stroma interface. Repeated therapy does not consistently enrich cells expressing these markers, although ER-negative cells accumulate. CONCLUSIONS: Commonly employed methods identify different cancer cell sub-populations with no consistent therapeutic implications, rather than a single population of cells. The relationships of breast cancer stem cells to clinical parameters will require identification of specific markers or panels for the individual cancer

SerpinB2 regulates stromal remodelling and local invasion in pancreatic cancer

Pancreatic cancer has a devastating prognosis, with an overall 5-year survival rate of ~8%, restricted treatment options and characteristic molecular heterogeneity. SerpinB2 expression, particularly in the stromal compartment, is associated with reduced metastasis and prolonged survival in pancreatic ductal adenocarcinoma (PDAC) and our genomic analysis revealed that SERPINB2 is frequently deleted in PDAC. We show that SerpinB2 is required by stromal cells for normal collagen remodelling in vitro, regulating fibroblast interaction and engagement with collagen in the contracting matrix. In a pancreatic cancer allograft model, co-injection of PDAC cancer cells and SerpinB2(-/-) mouse embryonic fibroblasts (MEFs) resulted in increased tumour growth, aberrant remodelling of the extracellular matrix (ECM) and increased local invasion from the primary tumour. These tumours also displayed elevated proteolytic activity of the primary biochemical target of SerpinB2-urokinase plasminogen activator (uPA). In a large cohort of patients with resected PDAC, we show that increasing uPA mRNA expression was significantly associated with poorer survival following pancreatectomy. This study establishes a novel role for SerpinB2 in the stromal compartment in PDAC invasion through regulation of stromal remodelling and highlights the SerpinB2/uPA axis for further investigation as a potential therapeutic target in pancreatic cancer

Mitochondrial mutations and metabolic adaptation in pancreatic cancer.

BACKGROUND: Pancreatic cancer has a five-year survival rate of ~8%, with characteristic molecular heterogeneity and restricted treatment options. Targeting metabolism has emerged as a potentially effective therapeutic strategy for cancers such as pancreatic cancer, which are driven by genetic alterations that are not tractable drug targets. Although somatic mitochondrial genome (mtDNA) mutations have been observed in various tumors types, understanding of metabolic genotype-phenotype relationships is limited. METHODS: We deployed an integrated approach combining genomics, metabolomics, and phenotypic analysis on a unique cohort of patient-derived pancreatic cancer cell lines (PDCLs). Genome analysis was performed via targeted sequencing of the mitochondrial genome (mtDNA) and nuclear genes encoding mitochondrial components and metabolic genes. Phenotypic characterization of PDCLs included measurement of cellular oxygen consumption rate (OCR) and extracellular acidification rate (ECAR) using a Seahorse XF extracellular flux analyser, targeted metabolomics and pathway profiling, and radiolabelled glutamine tracing. RESULTS: We identified 24 somatic mutations in the mtDNA of 12 patient-derived pancreatic cancer cell lines (PDCLs). A further 18 mutations were identified in a targeted study of ~1000 nuclear genes important for mitochondrial function and metabolism. Comparison with reference datasets indicated a strong selection bias for non-synonymous mutants with predicted functional effects. Phenotypic analysis showed metabolic changes consistent with mitochondrial dysfunction, including reduced oxygen consumption and increased glycolysis. Metabolomics and radiolabeled substrate tracing indicated the initiation of reductive glutamine metabolism and lipid synthesis in tumours. CONCLUSIONS: The heterogeneous genomic landscape of pancreatic tumours may converge on a common metabolic phenotype, with individual tumours adapting to increased anabolic demands via different genetic mechanisms. Targeting resulting metabolic phenotypes may be a productive therapeutic strategy

Cellular Robustness Conferred by Genetic Crosstalk Underlies Resistance against Chemotherapeutic Drug Doxorubicin in Fission Yeast

10.1371/journal.pone.0055041PLoS ONE81

Learning Optimal Strategies for Temporal Tasks in Stochastic Games

Synthesis from linear temporal logic (LTL) specifications provides assured controllers for systems operating in stochastic and potentially adversarial environments. Automatic synthesis tools, however, require a model of the environment to construct controllers. In this work, we introduce a model-free reinforcement learning (RL) approach to derive controllers from given LTL specifications even when the environment is completely unknown. We model the problem as a stochastic game (SG) between the controller and the adversarial environment; we then learn optimal control strategies that maximize the probability of satisfying the LTL specifications against the worst-case environment behavior. We first construct a product game using the deterministic parity automaton (DPA) translated from the given LTL specification. By deriving distinct rewards and discount factors from the acceptance condition of the DPA, we reduce the maximization of the worst-case probability of satisfying the LTL specification into the maximization of a discounted reward objective in the product game; this enables the use of model-free RL algorithms to learn an optimal controller strategy. To deal with the common scalability problems when the number of sets defining the acceptance condition of the DPA (usually referred as colors), is large, we propose a lazy color generation method where distinct rewards and discount factors are utilized only when needed, and an approximate method where the controller eventually focuses on only one color. In several case studies, we show that our approach is scalable to a wide range of LTL formulas, significantly outperforming existing methods for learning controllers from LTL specifications in SGs