317 research outputs found
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
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
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>
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
Long-term results from the EARLY study of bosentan in WHO functional class II pulmonary arterial hypertension patients.
Abstract
BACKGROUND:
The double-blind phase of the EARLY study of bosentan remains the only randomized controlled trial of a PAH-targeted therapy in World Health Organization functional class (FC) II patients. We report on the efficacy, safety, disease worsening, survival and prognostic factors in mildly symptomatic pulmonary arterial hypertension (PAH) patients treated with bosentan in the open-label extension phase of the EARLY study.
METHODS:
Exploratory efficacy outcomes included 6-minute walk distance (6 MWD) and WHO FC. Adverse events were recorded. Kaplan-Meier analysis was used to estimate time to first PAH worsening event (death, initiation of intravenous or subcutaneous prostanoids, atrial septostomy or lung transplantation) and survival. Cox regression analysis determined factors prognostic of survival.
RESULTS:
Median exposure to bosentan (n=173) was 51 months. At the end of the bosentan-treatment assessment period, 77.8% of patients were in WHO FC I/II. Adverse events led to discontinuation of bosentan in 20.2% of patients. Aminotransferase elevations>3× upper limit of normal occurred in 16.8%. Four-year PAH-event-free survival and survival were 79.5% (95% confidence intervals [95% CI] 73.4, 85.6) and 84.8% [95% CI 79.4, 90.2], respectively. Low 6 MWD, low mixed venous oxygenation, high N-terminal pro hormone of brain natriuretic peptide levels and PAH associated with connective tissue disease were associated with a higher risk of death.
CONCLUSIONS:
The majority of patients exposed to long-term bosentan maintained or improved their functional class. Approximately 20% of the patients discontinued treatment because of adverse events, which were most commonly PAH worsening and elevated liver enzymes
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
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